Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Endothelial Keratoplasty Safety-Basket Suture for Management of Difficult Cases.

PURPOSE: To describe a novel technique of a safety-basket for management of Descemet stripping automated endothelial keratoplasty in eyes with defects of the lens-iris diaphragm, postvitrectomized eyes, eyes with previous glaucoma tube-shunt or trabeculectomy, or when the patient cannot lie supine. METHODS: The safety-basket suture is placed after the endothelial graft has been positioned under air and all wounds have been closed. Double-armed 10-0 polypropylene suture on a curved needle is passed under the graft in a single-running fashion, a modification of the Masket technique used as a safety suture in the management of malpositioned intraocular lenses. Care is taken not to touch the graft with the needle or suture. The suture can be left in place and removed at the slit-lamp postoperatively with continued use of topical antibiotics while the safety-basket is left in place. RESULTS: The technique was used successfully for 35 high-risk cases with good success with no cases of postoperative infection. CONCLUSIONS: Endothelial keratoplasty safety-basket sutures, when used in high-risk Descemet stripping automated endothelial keratoplasty patients with abnormal anterior segment anatomy can provide support to maintain the graft in a central position and thus allow for easier rebubbling, should it detach in the early postoperative course.

Mammographic breast density refines Tyrer-Cuzick estimates of breast cancer risk in high-risk women: findings from the placebo arm of the International Breast Cancer Intervention Study I.

INTRODUCTION: Mammographic density is well-established as a risk factor for breast cancer, however, adjustment for age and body mass index (BMI) is vital to its clinical interpretation when assessing individual risk. In this paper we develop a model to adjust mammographic density for age and BMI and show how this adjusted mammographic density measure might be used with existing risk prediction models to identify high-risk women more precisely. METHODS: We explored the association between age, BMI, visually assessed percent dense area and breast cancer risk in a nested case-control study of women from the placebo arm of the International Breast Cancer Intervention Study I (72 cases, 486 controls). Linear regression was used to adjust mammographic density for age and BMI. This adjusted measure was evaluated in a multivariable logistic regression model that included the Tyrer-Cuzick (TC) risk score, which is based on classical breast cancer risk factors. RESULTS: Percent dense area adjusted for age and BMI (the density residual) was a stronger measure of breast cancer risk than unadjusted percent dense area (odds ratio per standard deviation 1.55 versus 1.38; area under the curve (AUC) 0.62 versus 0.59). Furthermore, in this population at increased risk of breast cancer, the density residual added information beyond that obtained from the TC model alone, with the AUC for the model containing both TC risk and density residual being 0.62 compared to 0.51 for the model containing TC risk alone (P =0.002). CONCLUSIONS: In women at high risk of breast cancer, adjusting percent mammographic density for age and BMI provides additional predictive information to the TC risk score, which already incorporates BMI, age, family history and other classic breast cancer risk factors. Furthermore, simple selection criteria can be developed using mammographic density, age and BMI to identify women at increased risk in a clinical setting. CLINICAL TRIAL REGISTRATION NUMBER: http://www.controlled-trials.com/ISRCTN91879928 (Registered: 1 June 2006).

A curious case of glaucoma?

An 84-year-old woman diagnosed with primary open-angle glaucoma was referred because her optic nerve appearance did not account for her visual field deficits. Further evaluation showed loss of color vision and rapid progression of visual field defects. Electroretinography revealed abnormal scotopic and photopic responses. Blood samples were positive for anti-retinal antibodies, but a malignancy work-up was negative, consistent with non-paraneoplastic autoimmune retinopathy.

Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study.

BACKGROUND: Mammographic breast density is a strong risk factor for breast cancer. Tamoxifen, which reduces the risk of breast cancer in women at high risk, also reduces mammographic breast density. However, it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug. METHODS: We conducted a nested case-control study within the first International Breast Cancer Intervention Study, a randomized prevention trial of tamoxifen vs placebo. Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5% increments. Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram, which took place 12-18 months after trial entry, and control subjects were 942 women without breast cancer. Multivariable logistic regression was used to adjust for other risk factors. All statistical tests were two-sided. RESULTS: In the tamoxifen arm, 46% of women had a 10% or greater reduction in breast density at their 12- to 18-month mammogram. Compared with all women in the placebo group, women in the tamoxifen group who experienced a 10% or greater reduction in breast density had 63% reduction in breast cancer risk (odds ratio = 0.37, 95% confidence interval = 0.20 to 0.69, P = .002), whereas those who took tamoxifen but experienced less than a 10% reduction in breast density had no risk reduction (odds ratio = 1.13, 95% confidence interval = 0.72 to 1.77, P = .60). In the placebo arm, there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10% reduction in mammographic density and subjects who experienced a greater reduction. CONCLUSION: The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.

Determinants of percentage and area measures of mammographic density.

Mammographic density is one of the strongest predictors of breast cancer risk. Typically expressed as a percentage of the breast area occupied by radiologically dense tissue on a mammogram, its full value may not be realized because of its negative association with body mass index. A simpler measure of mammographic density, independent of other breast cancer risk factors and equally predictive of risk, would be preferable for risk prediction models. Percentage and area measures of mammographic density were determined for 815 women at high risk for breast cancer from the baseline assessments in the International Breast Cancer Intervention Study I, a trial of tamoxifen for breast cancer prevention conducted between 1992 and 2001. Multivariate linear regression was used to assess associations between risk factors and the mammographic measures. Percent dense area was negatively associated with age, body mass index, menopausal status, predicted risk, and smoking status (R(2) = 24%). Dense area was negatively associated with only age and body mass index (R(2) = 7%), and the latter association was much weaker than for percent dense area. Nondense area was positively associated with age, body mass index, and predicted risk (R(2) = 36%). Dense area was not associated with the multitude of risk factors that percent dense area was, making it a simpler biomarker for risk prediction modeling. Both dense area and percent dense area should be presented whenever possible for comparisons in research.

Sun-protective behaviors in families at increased risk of melanoma.

The aim of this study was to compare reported behavior in the sun in melanoma families with that of geographical healthy controls and to determine the predictors of that behavior to inform the process of counseling melanoma families. One hundred and seventy individuals with a family history of melanoma and 140 controls completed a postal questionnaire. Thirty-one percent of relatives reported sunburn in the previous summer, compared with 41% of controls. Fifty-five percent of relatives had acquired a suntan so that adherence to health education advice was disappointing. Male relatives were particularly likely to report sunburn. Higher knowledge scores correlated well with greater belief in ability to prevent melanoma, less desire for a tan, and more protective behaviors in relatives only (not in controls). We have shown that some psychological characteristics, sex, and age have an effect on behavior, so that the educational approaches needed will vary. "Better" behaviors were reported by melanoma cases than other relatives and by members of families with larger numbers of cases, which suggests that a belief that an individual is at particular risk of melanoma is important for compliance with preventive behaviors.

Tamoxifen and breast density in women at increased risk of breast cancer.

BACKGROUND: Although mammographic breast density is associated with the risk of breast cancer and is influenced by hormone levels, the effects of tamoxifen on breast density in healthy women and whether tamoxifen-induced density changes are associated with breast cancer risk are unclear. We investigated mammographic breast density in healthy women with an increased risk of breast cancer at baseline and during 54 months of tamoxifen treatment. METHODS: Mammograms were reviewed from 818 breast cancer-free women (388 in the tamoxifen group and 430 in the placebo group) at high risk for breast cancer, from the International Breast Cancer Intervention Study I, a trial of tamoxifen for breast cancer prevention. Breast density measurements, at baseline and during treatment, were obtained at 12- to 18-month intervals. Multivariable analysis was used to assess associations with breast density. All statistical tests were two-sided. RESULTS: Breast density at baseline was similar in placebo (42.6%, 95% confidence interval [CI] = 39.6% to 45.6%) and tamoxifen (41.9%, 95% CI = 38.8% to 45.0%) groups. The main determinants of breast density at baseline were age, menopausal status, body mass index, and previous atypical hyperplasia. A greater density reduction in the tamoxifen group (7.9%, 95% CI = 6.9% to 8.9%) than in the placebo group (3.5%, 95% CI = 2.7% to 4.3%) was apparent within 18 months of treatment (P<.001); the reduction in density continued until 54 months of treatment. After 54 months of tamoxifen treatment, breast density was 28.2% (decrease from baseline = 13.7%, 95% CI = 12.3% to 15.1%; P<.001) in the tamoxifen group and 35.3% (decrease from baseline = 7.3%, 95% CI = 6.1% to 8.4%; P<.001) in the placebo group. The tamoxifen-associated density reduction was apparent in all subgroups, but there was a statistically significant interaction with age. In women aged 45 years or younger at entry, the net reduction with tamoxifen was 13.4% (95% CI = 8.6% to 18.1%), whereas in women older than 55 years, it was 1.1% (95% CI = -3.0% to 5.1%). CONCLUSION: Tamoxifen treatment was associated with reduction in breast density, most of which occurred during the first 18 months of treatment.

An assessment of the CDKN2A variant Ala148Thr as a nevus/melanoma susceptibility allele.

Melanocytic nevi are the most potent risk factors for melanoma yet identified. Variation in the nevus phenotype within a population is predominantly genetically determined. Genes that determine nevus expression may therefore act as low penetrance melanoma susceptibility genes. Rare germline mutations in CDKN2A predispose to melanoma and appear to be nevogenic, although the correlation between nevus phenotype and mutation status is poor. It is plausible that more common CDKN2A variants may influence both melanoma susceptibility and nevus susceptibility. Ala148Thr is a G to A missense polymorphism of CDKN2A, which is found in 4%-6% of the general population. We have investigated the role of Ala148Thr as a low penetrance melanoma or nevus susceptibility allele in two separate groups of individuals. The first was a sample of 488 adults recruited from 179 families of patients with the atypical nevus phenotype and/or a family history of melanoma, and the second was a population-based sample of 599 women. Similar prevalences of Ala148Thr (4.9% and 5.2%) were found in both samples but significant variation in the prevalence of the polymorphism was seen across geographic areas within England. There was no association between Ala148Thr status and nevus number or history of melanoma, and therefore the results did not support the hypothesis that the Ala148Thr variant is a low penetrance melanoma or nevus susceptibility allele. A significant protective role of Ala148Thr on the number of atypical nevi was observed in the family sample (mean of 1 atypical nevus in those with the allele and 3.5 nevi in those without, p = 0.02). After allowing for potential confounders this was not evident in the population-based sample.