Development of an intervention to manage knee osteoarthritis risk and symptoms following anterior cruciate ligament injury.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is a risk factor for developing knee osteoarthritis (OA). We developed an intervention to support people manage risk factors for OA. METHODS: We conducted one-on-one interviews with 20 individuals with OA symptoms 6-15 years post ACL injury and used a nominal group process during a workshop with 40 patients and healthcare professionals (HCPs) to elicit information on the intervention content and delivery characteristics (timing, HCPs, and methods). Interview data were analyzed using content analysis. Nominal group ideas with importance ratings ≥5 of 7 met criteria for inclusion. Results were integrated, considering similarities and differences. RESULTS: Eight content categories were identified: 1. understanding knee injury and expectations about recovery; 2. understanding OA risk; 3. understanding OA signs and symptoms; 4. managing OA risk; 5. managing knee OA symptoms; 6. information for influencers; 7. credible sources; and, 8. updates on new evidence and treatments. Delivery timing reflected a lifespan approach from time of injury through symptomatic knee OA management. Although multiple media for delivery were identified, introductory face-to-face discussions and opportunity for re-accessing HCPs were critical. All HCPs who treat people with ACL should be familiar with and able to deliver the intervention. CONCLUSIONS: This co-development approach identified that an intervention to support people with ACL injury to limit and manage knee OA requires content embedded within an easily accessible, multi-media delivery model with capacity for check-back with HCPs that is appealing to different age groups and personal preferences over the lifespan post injury.

White blood cell counts in healthy Jamaican adults.

The investigation of presumed neutropenia places a burden on the health services, especially those of developing countries, including Jamaica. This may be because the normal ranges used in the laboratory are based on the values generated from the Caucasian population. Previous studies looking at African and Afro-Caribbean groups have found lower counts for these populations compared with Caucasians. To address this issue, 195 healthy adults donating blood at the National Public Health Laboratory and the University Hospital of the West Indies blood banks in Kingston, Jamaica, were screened for complete blood count (CBC) differentials between June 2001 and June 2006. The geometric means for the neutrophil counts were found to be 2.4 x 10(9)/L for men and 2.7 x 10(9)/L for women, with 95% confidence intervals of 2.2-2.8 x 10(9)/L and 2.5-3.1 x 10(9)/L respectively. Values for the Jamaican population were similar to those of other Afro-Caribbean groups. Based on this distribution, 14% of healthy Jamaicans would fall below the normal ranges derived from Caucasians and therefore presumed to have neutropenia. We recommend that the lower reference ranges obtained for Afro-Caribbean adults be adopted for that population.

Using GIS to generate spatially balanced random survey designs for natural resource applications.

Sampling of a population is frequently required to understand trends and patterns in natural resource management because financial and time constraints preclude a complete census. A rigorous probability-based survey design specifies where to sample so that inferences from the sample apply to the entire population. Probability survey designs should be used in natural resource and environmental management situations because they provide the mathematical foundation for statistical inference. Development of long-term monitoring designs demand survey designs that achieve statistical rigor and are efficient but remain flexible to inevitable logistical or practical constraints during field data collection. Here we describe an approach to probability-based survey design, called the Reversed Randomized Quadrant-Recursive Raster, based on the concept of spatially balanced sampling and implemented in a geographic information system. This provides environmental managers a practical tool to generate flexible and efficient survey designs for natural resource applications. Factors commonly used to modify sampling intensity, such as categories, gradients, or accessibility, can be readily incorporated into the spatially balanced sample design.

Predicting water quality impaired stream segments using landscape-scale data and a regional geostatistical model: a case study in Maryland.

In the United States, probability-based water quality surveys are typically used to meet the requirements of Section 305(b) of the Clean Water Act. The survey design allows an inference to be generated concerning regional stream condition, but it cannot be used to identify water quality impaired stream segments. Therefore, a rapid and cost-efficient method is needed to locate potentially impaired stream segments throughout large areas. We fit a set of geostatistical models to 312 samples of dissolved organic carbon (DOC) collected in 1996 for the Maryland Biological Stream Survey using coarse-scale watershed characteristics. The models were developed using two distance measures, straight-line distance (SLD) and weighted asymmetric hydrologic distance (WAHD). We used the Corrected Spatial Akaike Information Criterion and the mean square prediction error to compare models. The SLD models predicted more variability in DOC than models based on WAHD for every autocovariance model except the spherical model. The SLD model based on the Mariah autocovariance model showed the best fit (r(2) = 0.72). DOC demonstrated a positive relationship with the watershed attributes percent water, percent wetlands, and mean minimum temperature, but was negatively correlated to percent felsic rock type. We used universal kriging to generate predictions and prediction variances for 3083 stream segments throughout Maryland. The model predicted that 90.2% of stream kilometers had DOC values less than 5 mg/l, 6.7% were between 5 and 8 mg/l, and 3.1% of streams produced values greater than 8 mg/l. The geostatistical model generated more accurate DOC predictions than previous models, but did not fit the data equally well throughout the state. Consequently, it may be necessary to develop more than one geostatistical model to predict stream DOC throughout Maryland. Our methodology is an improvement over previous methods because additional field sampling is not necessary, inferences about regional stream condition can be made, and it can be used to locate potentially impaired stream segments. Further, the model results can be displayed visually, which allows results to be presented to a wide variety of audiences easily.

Patterns of spatial autocorrelation in stream water chemistry.

Geostatistical models are typically based on symmetric straight-line distance, which fails to represent the spatial configuration, connectivity, directionality, and relative position of sites in a stream network. Freshwater ecologists have explored spatial patterns in stream networks using hydrologic distance measures and new geostatistical methodologies have recently been developed that enable directional hydrologic distance measures to be considered. The purpose of this study was to quantify patterns of spatial correlation in stream water chemistry using three distance measures: straight-line distance, symmetric hydrologic distance, and weighted asymmetric hydrologic distance. We used a dataset collected in Maryland, USA to develop both general linear models and geostatistical models (based on the three distance measures) for acid neutralizing capacity, conductivity, pH, nitrate, sulfate, temperature, dissolved oxygen, and dissolved organic carbon. The spatial AICC methodology allowed us to fit the autocorrelation and covariate parameters simultaneously and to select the model with the most support in the data. We used the universal kriging algorithm to generate geostatistical model predictions. We found that spatial correlation exists in stream chemistry data at a relatively coarse scale and that geostatistical models consistently improved the accuracy of model predictions. More than one distance measure performed well for most chemical response variables, but straight-line distance appears to be the most suitable distance measure for regional geostatistical modeling. It may be necessary to develop new survey designs that more fully capture spatial correlation at a variety of scales to improve the use of weighted asymmetric hydrologic distance measures in regional geostatistical models.

The linearity of the visual analogue scale in patients with severe acute pain.

The visual analogue scale (VAS) is a standard measurement tool in pain research and clinical practice, and has been shown to have linear scale properties for mild to moderate pain. Our aim was to evaluate the scaling properties of the VAS in subjects with severe acute pain. After Ethics Committee approval we studied 22 patients and asked them to rate the severity of their pain on a 100 mm VAS at the initial assessment (VAS1), and again after administration of analgesic medication. The subject was asked to nominate when they considered their pain intensity had halved, and at this time they were asked to rate this on a second VAS (VAS0.5). When the subject had received satisfactory relief of their pain, they were asked to describe how much their pain had been relieved and were then asked to rate their final pain state using a third VAS (VASfinal). The mean (SD) scores were VAS1 84 (14) (range 56-100), VAS0.5 42 (13) and VASfinal 21 (16). The mean (95% CI) for VASratio was 0.51 (0.45-0.57). The mean (SD) patients' estimate of pain relief was 77 (21)% from that of baseline, with a mean (SD) VASfinal 0.26 (0.20), 95% CI 0.17-0.38. The correlation of the patients' estimate of pain relief with the VASfinal was r=0.89, rho=0.87, both P<0.001. The VAS is a linear scale in subjects with severe acute pain. Changes in the VAS score represent a relative change in the magnitude of pain sensation.

The structure of variation and its influence on the estimation of status: indicators of condition of lakes in the Northeast, U.S.A.

One goal of regional-scale sample surveys is to estimate the status of a resource of interest from a statistically drawn representative sample of that resource. An expression of status is the frequency distribution of indicator scores capturing variability of attributes of interest. However, extraneous variability interferes with the status description by introducing bias into the frequency distributions. To examine this issue, we used data from a regional survey of lakes in the Northeast U.S. collected by the U.S. Environmental Protection Agency's Environmental Monitoring and Assessment Program (EMAP). We employ a components of variance model to identify sources of extraneous variance pertinent to status descriptions of physical, chemical, and biological attributes of the population of lakes in the NE. We summarize the relative magnitude of four components of variance (lake-to-lake, year, interaction, and residual) for each indicator and illustrate how extraneous variance biases the status descriptions. We describe a procedure that removes this bias from the status descriptions to produce unbiased estimates and introduce a novel method for estimating the 'cost' of removing the bias (expressed as either increased sampling uncertainty or additional samples needed to achieve the target precision in the absence of bias). We compare the relative magnitude of the four variance components across the array of indicators, finding in general that conservative chemical indicators are least affected by extraneous variance, followed by some nonconservative indicators, with nutrient indicators most affected by extraneous variance. Intermediate were trophic condition indicators (including sediment diatoms), fish species richness and individuals indicators, and zooplankton taxa richness and individuals indicators. We found no clear patterns in the relative magnitude of variance components as a function of several methods of aggregating fish and zooplankton indicators (e.g., level of taxonomy, or species richness vs. numbers of individuals).

The role of sample surveys for monitoring the condition of the nation's lakes.

In order to meet a growing need to determine the condition of the nation's ecosystems and how their condition is changing, the U.S. Environmental Protection Agency (EPA) developed EMAP, the Environmental Monitoring and Assessment Program. A common survey design serves as the foundation on which to base monitoring of status and trends among diverse ecosystem types. In this paper, we describe the need for a statistically based survey design, briefly summarize the basic EMAP design, describe how that design is tailored for the selection of a probability sample of lakes on which to make measurements of lake condition, and illustrate the process for selecting a sample of lakes in the northeastern United States. Finally, we illustrate how measurements taken on the sample of lakes can be summarized, with known uncertainty, to describe the condition of a population of lakes.

Demographic characteristics of ophthalmic outpatients at the Royal Victorian Eye and Ear Hospital.

To investigate demographic aspects of the access to services at the Royal Victorian Eye and Ear Hospital (RVEEH), routine registration records on outpatients were linked to the population of state health regions, the distribution of ophthalmologists and projected population growth. In the six-month period September 1990 to March 1991, 19,339 persons came to the hospital (Emergency Department or Outpatients) at least once with an eye problem. Most (93%) lived in the Melbourne metropolitan area. The largest group (40%) came from Health Region 6, the Western Metropolitan region, which also has the lowest density of ophthalmologists in Victoria (1.6 per 100,000 total population, excluding ophthalmologists in the central business district of Melbourne). In the sample, 7243 patients (37%) were aged 65 years or older. Of these older patients, 75% had multiple visits to the hospital for a given illness, compared with 30% in younger patients (P < 0.01). By application of projected age-group growth rates in the Victorian population to the current profile of RVEEH outpatients, we forecast a 32% increase in the number of outpatients attending the hospital over the 15 years to 2006, 10% more than the projected population growth of 22% over this period.

Isozyme analysis of progeny derived from (Allium fistulosum ×Allium cepa) ×Allium cepa.

Relatively large quantities of seed were obtained from the interspecific backcross (A. fistulosum xA. cepa) ×A. cepa allowing, for the first time, an extensive study of the heritable traits exhibited by backcross progeny. Two backcross populations, BC1034 and BC1040, distinguished by differentA. fistulosum parents, were characterized for the isozyme markersIdh-1, Adh-1, andPgi-1. Statistical methods are described to calculate cell probabilities for a mixed population of F2 and BC1 progeny, using an estimate of the fraction of F2 progeny in the population derived from the isozyme data. Cell probability distributions were calculated for a mixed population with independent pairs of loci and a mixed population with nonindependent pairs of loci. The isozyme lociIdh-1 andPgi-1 appear to be linked, with a map distance estimated at 33 centimorgans (cM) in BC1034 and 42 cM in BC1040. The probability distribution model for linked loci did not account for all of the distorted segregation ratios inIdh-1 ×Adh-1 orPgi-1 ×Adh-1. The cytological literature does not support linkage betweenIdh-1 ×Adh-1 orPgi-1 ×Adh-1. The distorted segregation ratios for these pairs of loci are likely the result of genetic incompatibilities between the two species.

An evaluation of oligoclonal banding and CSF IgG index in the diagnosis of neurosyphilis.

It can be difficult to determine which patients would benefit from therapy to control central nervous system infection with Treponema pallidum. The authors have followed patients prospectively to evaluate two new diagnostic tests available. They performed lumbar punctures on 107 consecutive patients with syphilis of unknown duration, untreated (n = 19) or with serology that did not decrease sufficiently during follow-up (n = 88). The mean age was 47 years, with 91 males and 16 females. Twelve had neurologic symptoms. In order to establish a gold standard, the authors required the cerebrospinal fluid Venereal Disease Research Laboratory (CSF VDRL) test to be reactive (n = 25). They then examined oligoclonal banding and CSF IgG index as diagnostic tests by comparing them to the gold standard. Oligoclonal banding, abnormal in 20, had a sensitivity of 52% and a specificity of 91%. The CSF IgG index, abnormal in 56, had a sensitivity of 92% and a specificity of 60%. The posttest likelihoods of a positive test result were low, and hence neither test ruled in the diagnosis. With a post-test likelihood (PTL) negative of 4%, a negative CSF IgG index assisted in ruling out the diagnosis. Oligoclonal banding was not a satisfactory test for neurosyphilis. The CSF IgG index appears to help only in ruling out infection. Further effort is needed in developing diagnostic tests to assist the clinician in the diagnosis of neurosyphilis.

Adjustment in covariance when one factor affects the covariate.

When a treatment influences both the primary response and the covariate, a standard analysis of covariance may misrepresent the real treatment effect by adjusting out that part of the effect which is manifest in the covariate. What parametric function should we examine if the treatments influence the covariate? An informative analysis would let the complete effects of the levels emerge, yet permit the effects to be adjusted to some standard conditions. To satisfy these requirements when the treatments have only one factor, treatment means should be adjusted to covariate values determined externally from the data. If instead the treatment structure has at least two factors, say columns and rows, which, respectively, affect and do not affect the covariate, an interpretable adjustment procedure would involve the response means in each column being adjusted to the column mean of the covariate. This change alters the computations of covariance, so the proposed analysis cannot easily be accommodated by widely-available computer packages. An example concerns beef cattle from various herds which are fed several diets. Herds influence initial weight, which is the covariate, but diets cannot affect the covariate.

Evaluation of automated enzyme immunoassays for five anticonvulsants and theophylline adapted to a centrifugal analyzer.

We report a clinical evaluation of the enzyme immunoassay (EMIT) performed with the GEMSAEC centrifugal analyzer as compared to gas-liquid and liquid chromatography for anticonvulsant drugs and theophylline, respectively. A good correlation was obtained for all drugs, although some difficulties were experienced with one lot of reagent for ethosuximide. The analyzer has an economic advantage if many samples are being analyzed for few drugs in each sample.

Studies of the glycine cleavage enzyme system in brain from infants with glycine encephalopathy.

Glycine content and enzyme activity of the glycine cleavage system were compared in autopsied brain from five infants dying with glycine encephalopathy and four control infants, including two with other types of hyperglycinemia. Glycine content was elevated 2- to 8-fold and glycine cleavage enzyme activity was undetectable in the brains of the glycine encephalopathy patients. Glycine content and enzyme activity were normal in the brains of the control patients, including one with ketotic hyperglycinemia secondary to methylmalonic acidemia. Prolonged dialysis failed to restore glycine cleavage enzyme activity in brain homogenates of glycine encephalopathy patients, and these homogenates failed to inhibit enzyme activity when added to homogenates of control brain. Radioactive bicarbonate was converted to radioactive glycine by control brain, but not by glycine encephalopathy brain. This finding, together with the results of recombination experiments between solubilized human brain enzymes and purified protein components of the bacterial glycine cleavage system of Arthrobacter globiformis, indicates that the enzyme defect in glycine encephalopathy involves at least the second or H protein of the 4-protein glycine cleavage enzyme system.

Lactic acidosis in three sibs due to defects in both pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes.

A Canadian Indian family is described in which three of the children were mentally retarded, and had seizures and other neurological abnormalities. They had chronic metabolic acidosis associated with elevated blood levels of lactate, pyruvate, and alanine. Two of the children excreted large amounts of pyruvic and alpha-ketoglutaric acids in the urine and had elevated plasma levels of glutamic acid and proline. Hypoglycemia occurred with fasting in two of the children. Treatment with pharmacological doses of thiamine, lipoic acid, biotin, riboflavin, and various dietary regimes was without effect. One child died at 3 1/2 months and another at 4 1/2 months; the third is still alive at 23 months of age. Enzyme assays revealed a low level of activity of both the pyruvate and alpha-ketoglutarate dehydrogenase complexes in cultured fibroblasts of one of the sibs. These patients appeared to have partial defects in the oxidation of pyruvate, as well as of alpha-ketoglutarate within the tricarboxylic acid cycle.