Understanding the minimum clinically important difference: a review of concepts and methods.

BACKGROUND CONTEXT: The effectiveness of spinal surgery as a treatment option is currently evaluated through the assessment of patient-reported outcomes (PROs). The minimum clinically important difference (MCID) represents the smallest improvement considered worthwhile by a patient. The concept of an MCID is offered as the new standard for determining effectiveness of a given treatment and describing patient satisfaction in reference to that treatment. PURPOSE: Our goal is to review the various definitions of MCID and the methods available to determine MCID. STUDY DESIGN: The primary means of determining the MCID for a specific treatment are divided into anchor-based and distribution-based methods. Each method is further subdivided and examined in detail. METHODS: The overall limitations of the MCID concept are first identified. The basic assumptions, statistical biases, and shortcomings of each method are examined in detail. RESULTS: Each method of determining the MCID has specific shortcomings. Three general limitations in the accurate determination of an MCID have been identified: the multiplicity of MCID determinations, the loss of the patient's perspective, and the relationship between pretreatment baseline and posttreatment change scores. CONCLUSIONS: An ideal means of determining the MCID for a given intervention is yet to be determined. It is possible to develop a useful method provided that the assumptions and methodology are initially declared. Our efforts toward the establishment of a MCID will rely on the establishment of specific external criteria based on the symptoms of the patient and treatment intervention being evaluated.     

Visual acuity results in school-aged children and adults: Lea Symbols chart versus Bailey-Lovie chart.

PURPOSE: To compare visual acuity results obtained using the Lea Symbols chart with visual acuity results obtained with the Bailey-Lovie chart in school-aged children and adults using a within-subjects comparison of monocular acuity results. METHODS: Subjects were 62 individuals between 4.5 and 60 years of age, recruited from patients seen in five optometry clinics. Each subject had acuity of the right eye and the left eye tested with the Lea Symbols chart and the Bailey-Lovie chart, with order of testing varied across subjects. Outcome measures were monocular logarithm of the minimum angle of resolution (logMAR) visual acuity and inter-eye acuity difference in logMAR units for each test. RESULTS: Correlation between acuity results obtained with the two charts was high. There was no difference in absolute inter-eye acuity difference measured with the two acuity charts. However, on average, Lea Symbols acuity scores were one logMAR line better than Bailey-Lovie acuity scores, and this difference increased with worse visual acuity. CONCLUSIONS: The Lea Symbols chart provides a measure of inter-eye difference that is similar to that obtained with the Bailey-Lovie chart. However, the monocular acuity results obtained with the Lea Symbols chart differ from those obtained with the Bailey-Lovie chart, and the difference is dependent on the individual's absolute level of visual acuity.     

Causes and types of health effects during the use of crop protection chemicals: data from a survey of over 6,300 smallholder applicators in 24 different countries

Purpose  The present investigation looks in detail at the causes and types of health incidents reported by 6,300 mainly smallholder agrochemical users in 24 countries during 2005 and 2006. Methods  The investigation is based on a questionnaire survey of knowledge, attitude and practice that concentrated on the sequence of events from purchasing the pesticide to disposal. Information was also collected about health problems experienced while using agrochemicals. The survey targeted mainly smallholder knapsack spray operators who were expected to be at a highest risk of exposure. Results  In the 12 months prior to interview, 1.2% of users reported an agrochemical-related incident that required hospital treatment, 5.8% reported an incident requiring at least trained medical treatment but not hospitalisation and 19.8% reported only a minor sign or symptom. Users who had experienced an incident involving agricultural equipment were 3.38 (95% CI 2.29–4.99) times more likely to experience an agrochemical-related health incident, but confident users who felt that their use of personal protective equipment while spraying was best practice were 0.60 (95% CI 0.44–0.84) times less likely to experience such an incident. Over 80% of product-related incidents were caused by insecticides and the incidence rate per spraying time for incidents linked to insecticides was significantly higher than that for fungicides or herbicides. Headache/dizziness and nausea/vomiting, often smell related, were the most common symptoms reported by users who listed agrochemical products that had caused them health problems (52 and 38% of product mentions, respectively). Conclusions  In most countries, the incidence of serious health effects was low; however, there was a high incidence of minor signs and symptoms in a few countries, especially in Africa. A disproportionate number of incidents occurred during insecticide use relative to the time that they were sprayed. Failure to exercise caution as indicated by whether users had incidents involving agricultural equipment or livestock, and lack of confidence in their practices were the most important predictors of agrochemical-related incidents.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

Predicting cerebral ischemia during carotid endarterectomy

We reviewed 86 consecutive patients undergoing elective carotid endarterectomy to determine whether preoperative clinical and angiographic data could be used to predict the risk of intraoperative cerebral ischemia during carotid occlusion. Electroencephalographic (EEG) monitoring with on-line Berg-Fourier transformation was carried out in all patients. A total of 32 patients (37.2%) underwent intraoperative shunting. Of these, 13 had no EEG changes but underwent shunting because of the surgeon's preference, while 19 patients underwent shunting because of EEG changes consistent with cerebral ischemia. There was one permanent (1.2%) and one transient (1.2%) neurologic deficit. Angiographic findings, clinical histories, and intraoperative EEGs were retrospectively reviewed to determine which risk factors best predicted the occurrence of intraoperative cerebral ischemia. Stroke within six weeks increased the risk of intraoperative cerebral ischemia 20-fold. Intracranial disease and contralateral carotid stenosis increased the risk of ischemia 17-fold and 16-fold, respectively. Statistical summation of all risk factors yielded a probability equation for EEG change that accurately quantitated pre-operative risk. Prospective application of this probability equation may simplify operative decision making if EEG monitoring is not available.     

Adiposity and sex hormones in girls.

Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone-binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 microg/dL compared with 78.8 microg/dL for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P(trend) = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P(trend) < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research.