The implantation effect: delay in seizure occurrence with implantation of intracranial electrodes.

OBJECTIVE: A transient decrease in seizure frequency has been identified during therapeutic brain stimulation trials with stimulator in patients in the inactive sham group. This study was performed to examine whether the implantation of intracranial electrodes decreases seizure occurrence and explores factors that may be associated. METHODS: A retrospective review of 193 patients was performed, all evaluated with both scalp video EEG monitoring and intracranial EEG (iEEG) monitoring. Data about the number of seizures per day during the monitoring period, the number of days until the first seizure, anti-epileptic drugs (AEDs), pain medications, types of implanted electrodes, and anesthetic agents were reviewed. We conducted a repeated measure analysis for counted data using generalized estimating equations with a log-link function and adjustment for number of days and anti-epileptic medication load on the previous day to compare seizure frequencies between scalp and iEEG monitoring. RESULTS: The time to the first seizure was significantly prolonged during iEEG monitoring as compared to scalp monitoring after correction for AED withdrawal (hazard ratio: 0.81, CI 0.69-0.96). During scalp video EEG monitoring, patients experienced an average of 1.09 seizures/day vs 1.27 seizures/day during iEEG monitoring (P=.066). There was no significant difference in seizure frequency in patients that received craniotomy vs burr holes only for intracranial implantation. An increasing number of electrodes implanted increased the delay to seizures (P=.01). Of all anesthetic agents used, desflurane seemed to have an anticonvulsive effect compared to other anesthetics (P=.006). Pain medication did not influence delay to seizures. SIGNIFICANCE: Seizures are delayed during iEEG as opposed to scalp monitoring illustrating the "implantation effect" previously observed. Surgical planning should account for longer monitoring periods, particularly when using larger intracranial arrays.

Second fractures among older adults in the year following hip, shoulder, or wrist fracture.

UNLABELLED: We report on second fracture occurrence in the year following a hip, shoulder or wrist fracture using insurance claims. Among 273,330 people, 4.3 % had a second fracture; risk did not differ by first fracture type. Estimated adjusted second fracture probabilities may facilitate population-based evaluation of secondary fracture prevention strategies. INTRODUCTION: The purpose of this study was estimate second fracture risk for the older US population in the year following a hip, shoulder, or wrist fracture. METHODS: Observational cohort study of Medicare fee-for-service beneficiaries with an index hip, shoulder, or wrist fragility fracture in 2009. Time-to-event analyses using Cox proportional hazards models to characterize the relationship between index fracture type (hip, shoulder, wrist) and patient factors (age, gender, and comorbidity) on second fracture risk in the year following the index fracture. RESULTS: Among 273,330 individuals with fracture, 11,885 (4.3 %) sustained a second hip, shoulder or wrist fracture within one year. Hip fracture was most common, regardless of the index fracture type. Comparing adjusted second fracture risks across index fracture types reveals that the magnitude of second fracture risk within each age-comorbidity group is similar regardless of the index fracture. Men and women face similar risks with frequently overlapping confidence intervals, except among women aged 85 years or older who are at greater risk. CONCLUSIONS: Regardless of index fracture type, second fractures are common in the year following hip, shoulder or wrist fracture. Secondary fracture prevention strategies that take a population perspective should be informed by these estimates which take competing mortality risks into account.

Cognitive effects of one season of head impacts in a cohort of collegiate contact sport athletes.

OBJECTIVE: To determine whether exposure to repetitive head impacts over a single season negatively affects cognitive performance in collegiate contact sport athletes. METHODS: This is a prospective cohort study at 3 Division I National Collegiate Athletic Association athletic programs. Participants were 214 Division I college varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration-time history of the head following impact, and 45 noncontact sport athletes. All athletes were assessed prior to and shortly after the season with a cognitive screening battery (ImPACT) and a subgroup of athletes also were assessed with 7 measures from a neuropsychological test battery. RESULTS: Few cognitive differences were found between the athlete groups at the preseason or postseason assessments. However, a higher percentage of the contact sport athletes performed more poorly than predicted postseason on a measure of new learning (California Verbal Learning Test) compared to the noncontact athletes (24% vs 3.6%; p < 0.006). On 2 postseason cognitive measures (ImPACT Reaction Time and Trails 4/B), poorer performance was significantly associated with higher scores on several head impact exposure metrics. CONCLUSION: Repetitive head impacts over the course of a single season may negatively impact learning in some collegiate athletes. Further work is needed to assess whether such effects are short term or persistent.

Lumbar discectomy outcomes vary by herniation level in the Spine Patient Outcomes Research Trial.

BACKGROUND: The Spine Patient Outcomes Research Trial showed an overall advantage for operative compared with nonoperative treatment of lumbar disc herniations. Because a recent randomized trial showed no benefit for operative treatment of a disc at the lumbosacral junction (L5-S1), we reviewed subgroups within the Spine Patient Outcomes Research Trial to assess the effect of herniation level on outcomes of operative and nonoperative care. METHODS: The combined randomized and observation cohorts of the Spine Patient Outcomes Research Trial were analyzed by actual treatment received stratified by level of disc herniation. Overall, 646 L5-S1 herniations, 456 L4-L5 herniations, and eighty-eight upper lumbar (L2-L3 or L3-L4) herniations were evaluated. Primary outcome measures were the Short Form-36 bodily pain and physical functioning scales and the modified Oswestry Disability Index assessed at six weeks, three months, six months, one year, and two years. Treatment effects (the improvement in the operative group minus the improvement in the nonoperative group) were estimated with use of longitudinal regression models, adjusting for important covariates. RESULTS: At two years, patients with upper lumbar herniations (L2-L3 or L3-L4) showed a significantly greater treatment effect from surgery than did patients with L5-S1 herniations for all outcome measures: 24.6 and 7.1, respectively, for bodily pain (p = 0.002); 23.4 and 9.9 for Short Form-36 physical functioning (p = 0.014); and -19 and -10.3 for Oswestry Disability Index (p = 0.033). There was a trend toward greater treatment effect for surgery at L4-L5 compared with L5-S1, but this was significant only for the Short Form-36 physical functioning subscale (p = 0.006). Differences in treatment effects between the upper lumbar levels and L4-L5 were significant for Short Form-36 bodily pain only (p = 0.018). CONCLUSIONS: The advantage of operative compared with nonoperative treatment varied by herniation level, with the smallest treatment effects at L5-S1, intermediate effects at L4-L5, and the largest effects at L2-L3 and L3-L4. This difference in effect was mainly a result of less improvement in patients with upper lumbar herniations after nonoperative treatment.

Markers of low level arsenic exposure for evaluating human cancer risks in a US population.

Epidemiologic studies conducted in the US have not previously detected an association between regional drinking water arsenic concentrations and corresponding cancer occurrence or mortality rates. To improve our estimation of cancer risk and arsenic exposure in the USA, we have investigated the reliability of several exposure markers. In the current study, we specifically evaluated the long-term reproducibility of tap water and toenail concentrations of arsenic, and the relation between water, toenail, and urinary measurement. Subjects included 99 controls in our case-control study on whom we requested a household tap water sample and toenail clipping three to five years apart. Additionally, participants were asked to provide a first morning void sample at the second interview. Tap water arsenic concentrations ranged from undetectable (<0.01 microg/L) to 66.6 microg/L. We found a significant correlation between both replicate water and toenail samples (intraclass correlation coefficient = 0.85, 95% confidence interval = 0.79-0.89 for water, and intraclass correlation coefficient = 0.60, 95% confidence interval = 0.48-0.70 for toenails). The inter-method correlations for water, urinary and toenail arsenic were all statistically significant (r = 0.35, p = 0.0024 for urine vs water; r = 0.33, p = 0.0016 for toenail vs water and r = 0.36, p = 0.0012 for urine vs toenails). Thus, we found both toenail and water measurements of arsenic reproducible over a three- to five-year period. Our data suggest that biologic markers may provide reliable estimates of internal dose of low level arsenic exposure that can be used to assess cancer risk.

Cryptogenic epilepsy: an infectious etiology?

PURPOSE: Cryptogenic epilepsy, the group of epilepsy syndromes for which an etiology is unknown, comprises approximately 20% of all epilepsy syndromes. We selected patients in this subgroup of epilepsy and tested them for evidence of Toxoplasma gondii IgG antibodies by the enzyme-linked immunosorbent assay. T. gondii is found in up to 20% of the U.S. population forming dormant brain cysts in the latent bradyzoite form. We investigated the hypothesis that dormant T. gondii infection might be associated with cryptogenic epilepsy. METHODS: We selected patients with cryptogenic epilepsies and tested them for evidence of T. gondii IgG antibodies by the enzyme-linked immunosorbent assay. A control group was also tested for comparison. RESULTS: We have found a statistically-significant elevation of T. gondii antibodies among cryptogenic epilepsy patients as compared to controls [59% increase in optical density (OD), p = 0.013]. This association persisted after adjustment for subjects' gender and age in a multiple logistic regression model; however, it was no longer as statistically significant. CONCLUSIONS: Our results suggest that chronic T. gondii infection with brain cysts may be a cause of cryptogenic epilepsy.

Children and guns in a well child cohort.

BACKGROUND: The purpose of this study was to estimate the extent of and to identify predictors of preadolescent gun use in a well child cohort with matched parent and child data. METHODS: We analyzed self-report questionnaires from children and their parents using conditional logistic regression models. Questionnaires were given to 3,145 ten- to twelve-year-old children and 3,145 parents enrolled by their pediatricians in a prevention cohort study. RESULTS: Thirty-two percent of the children lived in households with guns. Children and parents generally agreed about the presence of guns in their homes; 17% had access to unlocked guns in their homes; 22% had fired guns. In this preadolescent cohort, firing guns was associated with being male, having guns in the home, having friends who use guns, and initiation of alcohol use. CONCLUSIONS: In this well child cohort, significant numbers of preadolescent, healthy boys in white, middle-class U.S. homes have access to guns, are using guns, and have friends who use guns. These children are also early alcohol adopters. Safety interventions with parents of preadolescents about the risks for accidental injury, death, and suicide due to child gun use may prove beneficial.

Skin cancer risk in relation to toenail arsenic concentrations in a US population-based case-control study.

Arsenic is a known carcinogen specifically linked to skin cancer occurrence in regions with highly contaminated drinking water or in individuals who took arsenic-containing medicines. Presently, it is unknown whether such effects occur at environmental levels found in the United States. To address this question, the authors used data collected on 587 basal cell and 284 squamous cell skin cancer cases and 524 controls interviewed as part of a case-control study conducted in New Hampshire between 1993 and 1996. Arsenic was determined in toenail clippings using instrumental neutron activation analysis. The odds ratios for squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were close to unity in all but the highest category. Among individuals with toenail arsenic concentrations above the 97th percentile, the adjusted odds ratios were 2.07 (95% confidence interval (CI): 0.92, 4.66) for SCC and 1.44 (95% CI: 0.74, 2.81) for BCC, compared with those with concentrations at or below the median. While the risks of SCC and BCC did not appear elevated at the toenail arsenic concentrations detected in most study subjects, the authors cannot exclude the possibility of a dose-related increase at the highest levels of exposure experienced in the New Hampshire population.

Racial differences in pancreatic cancer: comparison of survival and histologic types of pancreatic carcinoma in Asians, blacks, and whites in the United States.

SEER data for histologically confirmed carcinomas of the pancreas for 1973-1995 from Hawaii, San Francisco, and Seattle (n = 10,621) were analyzed to compare the survival and types of carcinomas in various racial groups. These geographic sites were selected because each included a sizable number of Asian patients. The median survival after diagnosis in unadjusted data was longer in Asian patients than in whites. After adjustment for age at diagnosis and year of diagnosis, only the survival advantage of Asian women over whites and blacks persisted as a statistically significant difference. Racial differences were no longer statistically significant when further adjustments were made for stage, grade, and morphology. The proportion of papillary carcinomas or mucinous cystadenocarcinomas was higher in Asians than in whites and blacks (p = 0.02), and patients with these neoplasms had a longer median survival than did patients with ductal adenocarcinoma (12 vs. 3.3 months). The fraction of Asian patients with lower stages and grades of carcinomas also was higher than among white and black patients. Longer survival of Asian compared with white and black patients with pancreatic carcinoma is at least partly explained by their higher proportion of less aggressive carcinomas at the time of diagnosis.

Persistent increase in children's sun protection in a randomized controlled community trial.

BACKGROUND: Reducing sun exposure during childhood may prevent skin cancer later in life. Sun protection increased immediately following implementation of the SunSafe multicomponent, community-based intervention delivered in 1996 through schools, day care centers, primary care offices, and beach recreation areas. Whether sun protection levels would remain higher than preintervention levels the following summer was unknown. METHODS: A randomized controlled trial based in 10 New Hampshire towns addressed children's use of protective clothing, shade, and sunscreen at freshwater beach areas. The intervention was provided initially between March and May 1996. A brief project follow-up contact was provided to schools, day care centers, beaches, and primary care offices between March and May 1997 to restock intervention materials and to answer questions. Observations of 1490 children during June through August of 1997 were compared with observations made prior to any intervention between June and August of 1995. RESULTS: In intervention towns, the proportion of children using at least some sun protection increased by 0.15 from 0.58 in 1995 to 0.73 in 1997 while the proportion in control towns increased by 0.03 (P = 0.033). This increase was due to more use of sunscreen, but not more use of protective clothing or shade. In 1997, care-givers of children in intervention towns reported receiving more sun protection information from school and health care sources than control town caregivers (62% versus 33%, P < 0.006). CONCLUSIONS: In intervention communities, a higher proportion of children used sun protection in 1997 than at baseline. Increases from 1995 to 1997 were similar in magnitude to short-term increases between 1995 and 1996 that we have been previously reported.

Rectal mucosal proliferation and risk of colorectal adenomas: results from a randomized controlled trial.

Although rectal mucosal labeling index is thought to be a useful surrogate biomarker for colorectal cancer, the ability of the index to predict future neoplasia is unclear. We obtained rectal mucosal biopsies from 333 participants of a randomized controlled chemoprevention trial of calcium supplementation to determine whether labeling index was correlated with concurrent or future colorectal neoplasms. Labeling index was measured using proliferating cell nuclear antigen immunohistochemistry. Adenomas were enumerated at the time of the biopsies (cross-sectional) and 3 years later (prospective). We used logistic regression to test for an association of adenoma occurrence with overall labeling index, the mean proliferative height, and labeling index in the upper 40% of colon crypts. In the cross-sectional analysis, we found indications that higher proliferation was associated with an increase in the prevalence of adenomas. The overall adjusted odds ratios (OR) (95% confidence interval) were 1.14 (0.90-1.45) per % crypt labeling index, OR 1.08 (0.99-1.19) for upper crypt proliferation, and OR 1.07 (1.03-1.12) for proliferative height. In contrast, individuals with higher labeling index at baseline were actually less likely to have adenomas in the prospective analyses: OR 0.80 (0.62-1.02) per % crypt labeling index, OR 0.86 (0.73-1.00) for upper crypt index, and OR 0.97 (0.93-1.01) for proliferative height. Proliferative index does not predict future colorectal neoplasia, although it may be weakly associated with the presence of current adenomas. These results have important implications for the design of future intervention studies. Although it may be attractive to include the measurement of intermediate markers in large controlled trials, until we have more confidence in their performance, we should rely on better proven and more reliable intermediates, such as adenomas.

Measurement of low levels of arsenic exposure: a comparison of water and toenail concentrations.

A study was conducted to evaluate toenail arsenic concentrations as a biologic marker of drinking water arsenic exposure. Study subjects were controls in a US population-based case-control study of nonmelanoma skin cancer, randomly selected from drivers' license records (those < 65 years of age) and Medicare enrollment files (those > or = 65 years of age). Between 1994 and 1997, a total of 540 controls were interviewed and toenail samples of sufficient weight were collected from 506 (93.7%) of these. Beginning in 1995, a sample of tap water was taken from the participants' homes; a total of 217 (98.6%) water samples were obtained from the 220 subjects interviewed. Arsenic determinations were made from toenail samples using neutron activation analysis. Water samples were analyzed using hydride-generation magnet sector inductively coupled mass spectrometry. Among 208 subjects with both toenail and water measurements, the correlation (r) between water and nail arsenic was 0.65 (p < 0.001) among those with water arsenic concentrations of 1 microg/liter or higher and 0.08 (p = 0.31) among those with concentrations below 1 microg/liter (overall r = 0.46, p < 0.001). Our data suggest that toenail samples provide a useful biologic marker for quantifying low-level arsenic exposure.

The impact of spinal problems on the health status of patients: have we underestimated the effect?

STUDY DESIGN: A prospective study of 17,774 patients who consulted spine centers in which the impact of spinal disorders and comorbidities on physical functional status were evaluated. OBJECTIVES: To quantify the effect spinal diagnoses have on patients' physical functional status (SF-36 Physical Component Summary [PCS] score) compared with other common conditions and to quantify the effects of comorbidities on physical functional status in spine patients. SUMMARY OF BACKGROUND DATA: The burden of spinal conditions on a patient's function and the role that comorbidities play in this affliction are poorly quantified in the literature. METHODS: Data from the Health Survey Questionnaire were prospectively gathered through the National Spine Network, a nonprofit consortium of spine-focused practices. Each patient's SF-36 score was summarized into a single PCS score. The correlation between diagnosis and comorbidity and PCS score was assessed using multivariate linear regression. RESULTS: The study patients were a mean of 47.5 years of age, 54.7% were female, 52.3% had lumbosacral diagnoses, and 82.0% had had 3 or more months of pain. The population had a mean PCS score of 30.4 +/- 9.95 (SD) compared with 50.0 +/- 10.00 for the general United States population. The more comorbidities in a patient, the lower the PCS score (Spearman rank correlation = -0.27). The five comorbid conditions that lowered the PCS the most included congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), renal failure, rheumatoid arthritis, and lupus (all P <0.001). In multiple linear regression analysis, age, gender, diagnosis, and comorbidity explained 12.1% of the variance in PCS score. CONCLUSIONS: The PCS score is greatly affected in patients with spinal problems. The study population's PCS (30.4) was lower or similar to the PCS for patients with other illnesses reported in the literature: CHF (31.0), COPD (33.9), SLE (37.1), cancer (38.4), primary total hip arthroplasty (29.0), primary total knee arthroplasty (32.6), and glenohumeral degenerative joint disease (35.2). Further, the presence of comorbidity in spine patients adds to the burden of spinal conditions on functional status.

Classification of biopsy-confirmed brain tumors using single-voxel MR spectroscopy.

BACKGROUND AND PURPOSE: Our purpose was to develop a classification scheme and method of presentation of in vivo single-voxel proton spectroscopic data from astrocytomas that most closely match the classification scheme determined from biopsy specimens. Since in vivo proton spectroscopy is noninvasive, it may be an attractive alternative to intracranial biopsy. METHODS: Single-voxel spectra were acquired using the point-resolved spectroscopic pulse sequence as part of the Probe spectroscopy package on a G.E. 1.5-T Signa scanner. Subjects consisted of 27 patients with biopsy-confirmed brain tumors (13 with glioblastoma multiforme, six with anaplastic astrocytoma, and eight with low-grade astrocytoma). The patients were divided into groups based on the histologic subtype of their tumor for different treatment protocols. RESULTS: Metabolic peak areas were normalized for each metabolite (choline, creatine, N-acetylaspartate, lactate) to the area of the unsuppressed water peak and to the area of the creatine peak. Kruskal-Wallis nonparametric analysis of variance (ANOVA) tests showed statistically significant differences among the tumor groups for all the area ratios. The lactate/water ratio could be used to distinguished all three tumor groups, whereas the choline/water ratio distinguished low-grade astrocytomas from the two high-grade groups. Both the choline and lactate ratios could be used to separate the high-grade from the low-grade tumors. CONCLUSION: Specific relative metabolic peak area ratios acquired from regions of contrast-enhancing brain tumor can be used to classify astrocytomas as to histopathologic grade.

Confidence maps and confidence intervals for near infrared images in breast cancer.

This paper extends basic concepts of statistical hypothesis testing and confidence intervals to images generated by a new procedure for near infrared spectroscopic tomography being developed for use in breast cancer diagnosis. By estimating the covariance matrix of the pixels of an image from data used in the image reconstruction process, confidence maps for statistical tests on individual pixels and confidence intervals for entire images are displayed as an aid to research and clinical personnel interpreting possibly noisy images. The methods are applied to simulated and phantom-based images.

Maximum androgen-blockade with medical or surgical castration in advanced prostate cancer: A meta-analysis of nine published randomized controlled trials and 4128 patients using flutamide.

With the recent Southwest Oncology Group (SWOG) publication of their metastatic prostate cancer clinical trial results, which concluded that orchiectomy and flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does not significantly improve survival (NCI 0105), and the 1989 publication from the same cooperative group indicating a 24% improvement in survival for MAB therapy with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may well be undecided about the likelihood of clinical benefits with flutamide in combination with medical or surgical castration. To better characterize this important therapeutic decision, we assessed the survival benefit of MAB therapy with flutamide through a meta-analysis of up-to-date information from studies reported/conducted from 1989 through 1998. All peer-reviewed published randomized controlled trials comparing treatment with flutamide plus either lutenizing hormone releasing hormone (LhRH) agonists or orchiectomy as MAB treatment with LhRH or orchiectomy alone were included. The primary objective of the study was to form a combined estimate and confidence interval for the hazard ratio (as measured by the relative risk (RR) of survival in a comparison of castration vs MAB) summarizing the effect of flutamide treatment on overall survival. Directly extracted estimates of the log hazard ratio were used if available (1 study); if not, either an estimate of the RR based on a reported P-value from a log rank test (7 studies) or a discrete proportional hazards approximation based on reconstructed annual life tables for the treatment arms (1 study) were used. Nine studies with 4128 patients with advanced prostate cancer were included in these analyses. Pooled estimates demonstrated a 10% improvement in overall survival with flutamide as MAB therapy (relative risk (RR)=0.90, 95% Confidence Interval=0.79, 1.00). The currently available updated evidence from randomized trials shows a 10% benefit in overall survival with flutamide as MAB therapy in comparison to conventional castration, almost identical to the estimate reported in the recently published Southwest Oncology Group Study (NCI 0105).

A community-based randomized trial encouraging sun protection for children.

OBJECTIVE: We evaluated the impact of an intervention promoting sun protection behavior among children 2 to 11 years of age through schools and day care centers, primary care practices, and recreation areas. METHODS: Ten towns in New Hampshire were paired, then assigned randomly to intervention or control status. The multicomponent SunSafe intervention was provided to children and caregivers through primary care practices, day care centers, schools, and beach recreation areas. Training support and materials were provided by the SunSafe project, but project staff had no direct contact with children or parents in providing the intervention. All intervention components promoted the same message: avoid the sun between 11 AM and 3 PM, cover up using hats and protective clothing, use sun block with a sun protection factor >/=15, and encourage sun protection among family and friends. The impact of the intervention was determined by observing children's sun protection behavior at the beach during baseline compared with 1 year later. The primary outcomes of interest were changes in the proportion of children per town using at least some sun protection and changes in the proportion of children fully protected. Children were clustered by town, with the town thus being the unit of analysis. The primary care practice component included one practice meeting for clinicians and staff at which project staff presented background on skin cancer and how to promote its prevention; a sun protection office system manual based on our previous work, which provided specific direction on how to share responsibility among office staff and clinicians in carrying out routines that promote sun protection; and educational posters, pamphlets, and self-adhesive reminder notes designed to enhance sun protection counseling. SunSafe removable tattoos and stickers were offered to children at well-child and illness visits during the summer months. Schools each received three project staff visits: a brief visit with the principal to describe the intervention and to answer questions; an in-service program to educate teachers about skin cancer and to introduce curricular materials; and help with one parent outreach program. Larger day care centers each received one project staff visit. An additional six smaller day care centers received curricular materials through the mail but no visits. Two similar sets of curricular materials were used, one for grade schools and the other for preschools and day care centers. Both emphasized the importance of sun protection rather than the danger of skin cancer. Materials emphasized dynamic activities modeled after the "Slip, Slop, Slap" and "SunSmart" programs and included new material developed to suit regional needs. Both manuals offered structured plans but also provided a variety of activities from which teachers could choose. Teachers agreed to devote a minimum of two class periods to these materials. For recreation areas, lifeguards in each of the intervention communities attended an in-service meeting, during which background about skin cancer prevention was presented by project staff. The project also provided displays about the ultraviolet (UV) light index and about sun protection to be posted at each beach. Subsequently, project staff called beach staff in each community each morning with the predicted UV index for the day to post on the display. Educational pamphlets about the UV index and free sun-block samples were available to beachgoers through the lifeguards. One brief follow-up visit by project staff was made to each beach area to provide reinforcement. RESULTS: We observed 1930 children. Use of some sunscreen on at least one body area increased in all 5 intervention towns compared with paired control towns. In intervention towns, this mean proportion increased from 0.56 of those observed at baseline to 0.76 of those observed postintervention, with a minimal increase among control town children. (ABSTRACT TRUNCATED

Covariate measurement error and the estimation of random effect parameters in a mixed model for longitudinal data.

We explore the effects of measurement error in a time-varying covariate for a mixed model applied to a longitudinal study of plasma levels and dietary intake of beta-carotene. We derive a simple expression for the bias of large sample estimates of the variance of random effects in a longitudinal model for plasma levels when dietary intake is treated as a time-varying covariate subject to measurement error. In general, estimates for these variances made without consideration of measurement error are biased positively, unlike estimates for the slope coefficients which tend to be 'attenuated'. If we can assume that the residuals from a longitudinal fit for the time-varying covariate behave like measurement errors, we can estimate the original parameters without the need for additional validation or reliability studies. We propose a method to test this assumption and show that the assumption is reasonable for the example data. We then use a likelihood-based method of estimation that involves a simple extension of existing methods for fitting mixed models. Simulations illustrate the properties estimators.

Effects of milk and milk products on rectal mucosal cell proliferation in humans.

Intake of dairy products and major dairy constituents (e.g., calcium) has been proposed to reduce the risk of colorectal cancer, although epidemiological studies have yielded inconclusive results. We conducted a randomized cross-over trial to test the effects of high- and low-dairy consumption diets on rectal mucosal proliferation, a possible intermediary marker for large bowel cancer. From a gastroenterology clinic at an academic medical center, we recruited 40 patients, ages 25-79 years, who had either a history of a large bowel adenoma or a first-degree relative with large bowel cancer. Participants completed a baseline questionnaire covering demographic characteristics, health history, and habits and a food frequency questionnaire. They were randomized to a 12-week diet of either high dairy intake (six dairy servings/day) or low dairy intake (<0.5 serving of dairy products/day), with an intervening 12-week washout period in which they were asked to resume their usual diet before crossing over to the alternate study diet for the last 12-week period of the study. Adherence to the study diets was monitored by a daily dairy intake checklist and periodic, unscheduled 24-h dietary recalls. Biopsies of the rectal mucosa were obtained at the beginning and end of each intervention phase. Two assays of rectal mucosal cell proliferation were performed: immunohistochemical determination of proliferating cell nuclear antigen and whole crypt mitotic count. We found no statistically significant changes in either of these proliferation measures as a result of high or low dairy intake. There was no correlation between the labeling index for proliferating cell nuclear antigen and whole crypt mitotic count; however, measures of the location and intensity of cell proliferation within the rectal crypt were highly correlated between the two assays. Thus, our study indicates that greater consumption of dairy products over a 12-week period does not change rectal mucosal cell proliferation.

Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population.

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic.