Outbreak of Anthrax in Livestock with Human Occupational Exposures - Minnesota, 2023.

In July 2023, the Minnesota Department of Health (MDH) was notified of possible occupational exposures to anthrax during an outbreak in animals. In consultation with the Centers for Disease Control and Prevention, MDH epidemiologists created a questionnaire that assessed exposure risks and helped determine individual illness monitoring and antibiotic post-exposure prophylaxis needs. This investigation and the resources developed for it could be useful in future scenarios where there are occupational exposures to naturally occurring anthrax.

Modelling uptake and transport of therapeutic agents through the lymphatic system.

The ability of the lymphatic network to absorb large molecules and bypass the first-pass liver metabolism makes it appealing as a delivery system for therapeutic substances. In most cases, the drug is injected into the subcutaneous tissue and must negotiate the tissue space, before being drained via the lymphatics. Tracking the transport of drug molecules through this route is challenging, and computational models of lymphatic drainage can play an important role in assessing the efficacy of a proposed delivery strategy. The three-dimensional computational model we present here of the peripheral lymphatic network and surrounding interstitium is informed by anatomical data, and quantifies the degree to which uptake and transit times are affected by drug particle size, physiological flow rates, and specifics of drug injection.

Quality of life in breast cancer survivors: An assessment of international breast cancer dragon boat racers.

Resistance exercise is deemed safe for women recovering from conventional breast cancer therapies but few clinicians are aware that dragon boat racing, as a form of resistive exercise, is available to the breast cancer community. The objectives of this study were to 1) increase clinician awareness of dragon boat racing (DBR) in breast cancer survivors as a community-based physical activity, and 2) evaluate quality of life (QOL) in breast cancer survivors with or without lymphedema who participate in DBR. This prospective, observational study surveyed 1,069 international breast cancer dragon boat racers from eight countries to compare function, activity, and participation in women with and without selfreported lymphedema using the Lymph-ICF questionnaire. Seventy-one percent of women (n=758) completed the questionnaires. Results revealed significantly higher Lymph-ICF scores in the lymphedema participants, signifying reduced QOL, when compared to the nonlymphedema participants (p<0.05), except for "go on vacation" for which no statistical difference was reported (p=0.20). International breast cancer survivors with lymphedema participating in DBR at an international competition had reduced function, limited activity, and restricted participation compared to participants without lymphedema. Clinicians should consider utilizing DBR as a community-based activity to support exercise and physical activity after a breast cancer diagnosis.

Development of an in situ procedure to evaluate the reticulo-rumen morphology of sheep selected for divergent methane emissions.

Published studies have shown that methane yield (g CH4/kg dry matter) from sheep is positively correlated with the size (volume and surface area) of the reticulo-rumen (RR) and the weight of its contents. However, the relationship between CH4 yield and RR shape has not been investigated. In this work, shape analysis has been performed on a data set of computerised tomography (CT) scans of the RR from sheep having high and low CH4 yields (n=20 and n=17, respectively). The three-dimensional geometries of the RRs were reconstructed from segmented scan data and split into three anatomical regions. An iterative fitting technique combining radial basis functions and principal component (PC) fitting was used to create a set of consistent landmarks which were then used as variables in a PC analysis to identify shape variation within the data. Significant size differences were detected for regions corresponding to the dorsal and ventral compartments between sheep with high and low CH4 yields. When the analysis was repeated after scaling the geometries to remove the effect of size, there was no significant shape variation correlating with CH4 yield. The results have demonstrated the feasibility of CT-based computational shape determination for studying the morphological characteristics of the RR and indicate that size, but not shape correlates with CH4 yield in sheep.

Carbon dioxide insufflation deflects airborne particles from an open surgical wound model.

BACKGROUND: Surgical site infections remain a significant burden on healthcare systems and may benefit from new countermeasures. AIM: To assess the merits of open surgical wound CO2 insufflation via a gas diffuser to reduce airborne contamination, and to determine the distribution of CO2 in and over a wound. METHODS: An experimental approach with engineers and clinical researchers was employed to measure the gas flow pattern and motion of airborne particles in a model of an open surgical wound in a simulated theatre setting. Laser-illuminated flow visualizations were performed and the degree of protection was quantified by collecting and characterizing particles deposited in and outside the wound cavity. FINDINGS: The average number of particles entering the wound with a diameter of <5µm was reduced 1000-fold with 10L/min CO2 insufflation. Larger and heavier particles had a greater penetration potential and were reduced by a factor of 20. The degree of protection was found to be unaffected by exaggerated movements of hands in and out of the wound cavity. The steady-state CO2 concentration within the majority of the wound cavity was >95% and diminished rapidly above the wound to an atmospheric level (∼0%) at a height of 25mm. CONCLUSION: Airborne particles were deflected from entering the wound by the CO2 in the cavity akin to a protective barrier. Insufflation of CO2 may be an effective means of reducing intraoperative infection rates in open surgeries.

An Experimental and Numerical Investigation of CO2 Distribution in the Upper Airways During Nasal High Flow Therapy.

Nasal high flow (NHF) therapy is used to treat a variety of respiratory disorders to improve patient oxygenation. A CO2 washout mechanism is believed to be responsible for the observed increase in oxygenation. In this study, experimentally validated Computational Fluid Dynamics simulations of the CO2 concentration within the upper airway during unassisted and NHF assisted breathing were undertaken with the aim of exploring the existence of this washout mechanism. An anatomically accurate nasal cavity model was generated from a CT scan and breathing was reproduced using a Fourier decomposition of a physiologically measured breath waveform. Time dependent CO2 profiles were obtained at the entrance of the trachea in the experimental model, and were used as simulation boundary conditions. Flow recirculation features were observed in the anterior portion of the nasal cavity upon application of the therapy. This causes the CO2 rich gas to vent from the nostrils reducing the CO2 concentration in the dead space and lowering the inspired CO2 volume. Increasing therapy flow rate increases the penetration depth within the nasal cavity of the low CO2 concentration gas. A 65% decrease in inspired CO2 was observed for therapy flow rates ranging from 0 to 60 L min(-1) supporting the washout mechanism theory.

A boundary-integral representation for biphasic mixture theory, with application to the post-capillary glycocalyx.

We describe a new boundary-integral representation for biphasic mixture theory, which allows us to efficiently solve certain elastohydrodynamic-mobility problems using boundary element methods. We apply this formulation to model the motion of a rigid particle through a microtube which has non-uniform wall shape, is filled with a viscous Newtonian fluid, and is lined with a thin poroelastic layer. This is relevant to scenarios such as the transport of small rigid cells (such as neutrophils) through microvessels that are lined with an endothelial glycocalyx layer (EGL). In this context, we examine the impact of geometry upon some recently reported phenomena, including the creation of viscous eddies, fluid flux into the EGL, as well as the role of the EGL in transmitting mechanical signals to the underlying endothelial cells.

Circumscribed choroidal hemangioma: clinical manifestations and factors predictive of visual outcome in 200 consecutive cases.

PURPOSE: To review the clinical features and management of circumscribed choroidal hemangioma and determine factors predictive of poor visual outcome. DESIGN: Retrospective consecutive noncomparative interventional case series. PARTICIPANTS: Two hundred consecutive patients with circumscribed choroidal hemangioma. MAIN OUTCOME MEASURES: The main outcome measures were analyzed in 155 patients with follow-up of at least 3 months and included complete resolution of subretinal fluid, worsening of visual acuity (more than 2 Snellen lines), and poor final visual acuity (20/200 or worse). RESULTS: The patients were seen at a mean age of 45 years with symptoms of decreased visual acuity (81%), visual field defect (7%), metamorphopsia (3%), floaters (2%), progressive hypermetropia (1%), photopsia (1%), pain (1%), and no symptoms (6%). The referring diagnoses were choroidal hemangioma (29%), choroidal melanoma (29%), choroidal metastasis (9%), retinal detachment (6%), central serous chorioretinopathy (5%), and others. The tumor had a median base of 6.0 mm and median thickness of 3.0 mm. Secondary retinal detachment in the foveal region was present in 81% of the patients. Initial treatment included observation (51%), laser photocoagulation (44%), plaque radiotherapy (4%), external beam radiotherapy (1%), surgical repair of retinal detachment (1%), and enucleation for painful neovascular glaucoma (1%). Kaplan-Meier estimates revealed complete resolution of subretinal fluid in 60% patients at 5 years and 76% patients at 10 years follow-up. By multivariable analysis, clinical factors predictive of complete resolution of subretinal fluid included shorter duration of symptoms (P = 0.03) and inferior quadrant location of tumor (P = 0.001). At initial presentation, 82 of 155 (53%) patients had poor visual acuity (20/200 or worse), and 73 of 155 (47%) patients had good to moderate visual acuity (20/100 or better). Of those 82 patients with poor initial vision, poor final vision was found in 54% at 5 years and 80% at 10 years. Of the 73 patients with good to moderate initial vision, poor final vision was found in 12% at 5 years and 43% at 10 years. By multivariable analysis, clinical factors predictive of poor final visual acuity included poor initial visual acuity (P < 0.001), failure of previous laser photocoagulation before referral (P = 0.01), and tumor management with observation after referral (P = 0.02). Worsening of visual acuity (by more than 2 Snellen lines) was observed in 8% at 5 years and 28% at 10 years of those 82 patients who were initially seen with poor vision. Worsening of visual acuity was found in 10% at 5 years and 30% at 10 years of those 73 patients who initially were seen with good to moderate vision. CONCLUSIONS: Circumscribed choroidal hemangioma is a rare intraocular tumor. In 38% of cases, this tumor is initially misinterpreted before referral as choroidal melanoma or metastasis. Visual acuity is poor in more than 60% of patients at 10 years, despite successful control of associated subretinal fluid in 76% patients.

Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors.

OBJECTIVE: To evaluate the clinical factors predictive for tumor recurrence and treatment complications in a large series of children who underwent plaque radiotherapy for retinoblastoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The participants included 141 children with retinoblastoma who were managed on the Oncology Service at Wills Eye Hospital with plaque radiotherapy between July 1976 and June 1999. MAIN OUTCOME MEASURES: Tumor recurrence and treatment complications. RESULTS: There were 208 tumors managed with plaque radiotherapy. The mean patient age at plaque treatment was 19 months. Prior treatment to the retinoblastoma of concern was delivered to 148 tumors (71%) and included various combinations of treatments such as intravenous chemoreduction, external beam radiotherapy, laser photocoagulation, thermotherapy, and cryotherapy. For 72 retinoblastomas (35%), more than one therapeutic method had failed to achieve tumor control before the use of plaque radiotherapy. Of the 208 retinoblastomas managed with plaque radiotherapy, Kaplan-Meier estimates of tumor control were 83% at 1 year and 79% at 5 years. Of the 60 tumors treated only with plaque radiotherapy (primary treatment), recurrence at 1 year was 12%. Of the 148 tumors treated after failure of other methods (secondary treatment), specific Kaplan-Meier estimates of tumor recurrence at 1 year was detected in 8% of tumors previously treated with chemoreduction, 25% of tumors previously treated with external beam radiotherapy, 34% tumors previously treated with both chemoreduction and external beam radiotherapy, and 8% of tumors previously treated with laser photocoagulation, thermotherapy, or cryotherapy (methods other than chemoreduction and external beam radiotherapy). Using multivariable analysis, the risks for tumor recurrence included the presence of tumor seeds in the vitreous, presence of subretinal tumor seeds, and increasing patient age. Using Kaplan-Meier estimates, radiation complications at 5 years of follow-up included nonproliferative retinopathy in 27%, proliferative retinopathy in 15%, maculopathy in 25%, papillopathy in 26%, cataract in 31%, glaucoma in 11%, and scleral necrosis in 0%. CONCLUSIONS: Plaque radiotherapy for retinoblastoma provides tumor control in 79% of cases at 5 years of follow-up. It is particularly useful for those tumors that fail treatment with chemoreduction, laser photocoagulation, thermotherapy, and cryotherapy. Tumors in young patients without vitreous or subretinal seeding show the best long-term control.

Olanzapine versus haloperidol in children with autistic disorder: an open pilot study.

OBJECTIVES: Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment. METHOD: In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Children's Psychiatric Rating Scale (CPRS). RESULTS: Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain. CONCLUSIONS: The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.

Classification and management of Coats disease: the 2000 Proctor Lecture.

PURPOSE: To review the methods and results of management in a large series of patients with Coats disease, to determine risk factors for poor visual outcome and enucleation, and to propose a practical classification of Coats disease. METHODS: In a retrospective consecutive series in 150 patients, Coats disease was defined as idiopathic retinal telangiectasia with intraretinal or subretinal exudation without appreciable signs of retinal or vitreal traction. We reviewed our experience with management, including observation, laser photocoagulation, cryotherapy, and various techniques of retinal detachment surgery and enucleation. The anatomic outcome, complications of treatment, visual results, and reasons for enucleation were tabulated. Factors predictive of poor visual outcome (20/200 or worse) and enucleation were determined using Cox proportional hazards regression models. Based on these observations, a staging classification of Coats disease, applicable to treatment selection and ocular prognosis, is proposed. RESULTS: In 117 patients (124 eyes) with a mean follow up of 55 months (range, 6 months to 25 years) primary management was observation in 22 eyes (18%), cryotherapy in 52 (42%), laser photocoagulation in 16 (13%), various methods of retinal detachment surgery in 20 (17%), and enucleation in 14 (11%). Anatomic improvement or stability was achieved in 76% of eyes, and final visual acuity was 20/50 or better in 17 eyes (14%), 20/60 to 20/100 in eight (6%), 20/200 to finger counting in 30 (24%), and hand motion to no light perception in 49 (40%) Enucleation was ultimately necessary in 20 eyes (16%). Risk factors predictive of poor visual outcome (20/200 or worse) included postequatorial (P =.01), diffuse (P =.01), or superior (P =.04) location of the telangiectasias and exudation, failed resolution of subretinal fluid after treatment (P =.02), and presence of retinal macrocysts (P =.02). The main risk factors for enucleation were elevated intraocular pressure (greater than 22 mm Hg; P less than or equal to.001) and iris neovascularization (P less than or equal to.001). Coats disease was classified into stage 1, telangiectasia only; stage 2, telangiectasia and exudation (2A, extrafoveal exudation; 2B, foveal exudation) stage 3, exudative retinal detachment (3A, subtotal; 3B, total); stage 4, total detachment and secondary glaucoma; and stage 5, advanced end-stage disease. Poor visual outcome (20/200 or worse) was found in 0% of eyes with stage 1, 53% with stage 2, 74% with stage 3, and 100% of stages 4 and 5 Coats disease. Enucleation was ultimately necessary in 0% of stages 1 and 2, 7% of stage 3, 78% of stage 4, and 0% of stage 5 disease. CONCLUSIONS: Carefully selected treatment can anatomically stabilize or improve the eye with Coats disease in 76% of eyes. However, poor visual outcome of 20/200 or worse commonly results. Patients who present with stages 1 to 3 Coats disease have the best visual prognosis, and patients with stages 4 and 5 have a poor visual prognosis.

Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients.

OBJECTIVE: To identify the risk factors of conjunctival malignant melanoma that predict local tumor recurrence, orbital exenteration, distant metastasis, and tumor-related mortality. DESIGN: The clinical parameters of the patient, tumor, and treatment were analyzed in a nonrandomized fashion for their relation to 4 main outcome measures using Cox proportional hazards regression models. PARTICIPANTS: One hundred fifty consecutive patients. MAIN OUTCOME MEASURES: Local tumor recurrence, orbital exenteration, distant metastasis, and death from conjunctival melanoma. RESULTS: The Kaplan-Meier estimates of local tumor recurrence was 26% at 5 years, 51% at 10 years, and 65% at 15 years. The mean number of recurrences per patient was 1 (median, 0 recurrences). There was no recurrence in 98 patients (65%), 1 recurrence in 28 patients (19%), 2 recurrences in 11 patients (7%), 3 recurrences in 5 patients (3%), and 4 or more recurrences in 8 patients (5%). Using multivariate analysis, the factors correlated with local tumor recurrence were melanoma location (not touching the limbus) (P =.01) and pathological tumor margins (lateral margin involved) (P =.02). Multivariate analysis for features correlated with ultimate exenteration included initial visual acuity (20/40 OU or worse) (P<. 001), melanoma color red (P =.01), and melanoma location (not touching the limbus) (P =.02). Tumor metastasis was present in 16% of patients at 5 years, 26% of patients at 10 years, and 32% of patients at 15 years. Metastasis was first located in the regional lymph nodes in 17 cases, the brain in 4 cases, the liver in 3 cases, the lung in 2 cases, and was disseminated in 1 case. The risks for metastases using multivariate analysis included pathological tumor margins (lateral margin involved) (P =.002) and melanoma location (not touching limbus) (P =.04). Tumor-related death occurred in 7% patients at 5 years' follow-up and 13% at 8 years' follow-up. The risk factors for death using multivariate analysis included initial symptoms (lump) (P =.004) and pathologic findings (de novo melanoma without primary acquired melanosis) (P =.05). The technique of initial surgery was shown to be an important factor in preventing eventual tumor recurrence (P =.07), metastasis (P =.03), and death (P =.006) in the univariate analysis, but did not reach significance in the multivariate analysis. CONCLUSIONS: Conjunctival malignant melanoma is a potentially deadly tumor. In the present study, metastasis was detected in 26% of patients, and death occurred in 13% of patients at 10 years. Extralimbal melanoma and tumor involvement of the surgical margins were especially poor prognostic factors. Meticulous surgical planning using wide microsurgical excisional biopsy working with the "no touch" technique and supplemental alcohol corneal epitheliectomy and conjunctival cryotherapy is advised. Arch Ophthalmol. 2000;118:1497-1507

Plaque radiotherapy for management of ciliary body and choroidal melanoma with extraocular extension.

PURPOSE: To report the results of plaque radiotherapy of ciliary body and choroidal melanoma with extraocular extension. METHODS: This retrospective study of 17 eyes of 17 patients with ciliary body and choroidal melanoma demonstrated extraocular extension that was clinically evident but less than 3 mm in thickness. In 14 eyes, the extraocular extension was located anteriorly and in three posteriorly. The outcome of plaque radiotherapy in terms of intraocular and extraocular tumor responses and the development of metastasis were analyzed. RESULTS: At a median follow-up of 63 months (range, 23 to 164 months) after plaque radiotherapy, all patients showed control of both the intraocular and extraocular components of ciliary body and choroidal melanoma. In no case did the intraocular or extraocular portion of the tumor relapse. The initial median thickness of the intraocular component was 4.9 mm, and the final median thickness was 2.4 mm. The initial median thickness of the extraocular component was 2.0 mm, and the final median thickness was 1.0 mm. The initial median basal diameter of the extraocular component was 3.5 mm, and the final median basal diameter was 2.0 mm. Of 17 patients, 11 (10 with anterior and one with posterior extraocular extension) showed partial regression in base and thickness of the extraocular extension, and in six there was little or no change. In those with anterior extrascleral extension, the sclera remained intact without clinically observable necrosis, and the scleral fibers were gradually more visible as the tumor regressed. Three patients (18%) died of metastatic melanoma at a median interval of 38 months after plaque radiotherapy. CONCLUSIONS: Plaque radiotherapy appears to be a reasonable treatment option for selected cases of ciliary body and choroidal melanoma with clinically visible extraocular extension less than 3 mm in thickness.

Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients.

OBJECTIVE: To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. DESIGN: Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. PARTICIPANTS: Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. MAIN OUTCOME MEASURES: Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [> or = 5 lines Snellen visual acuity]). RESULTS: Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (< or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. CONCLUSIONS: Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder.

BACKGROUND: A subgroup of children and adolescents with conduct disorder are characterized by severe and persistent aggression. Although there is no agreed on treatment for such aggression, lithium carbonate has shown promise in some studies involving children. Our study was designed to critically assess the efficacy of lithium in the treatment of aggression in children and adolescents using a measure specific for aggression. METHODS: Subjects were inpatients with conduct disorder hospitalized because of severe and chronic aggression. A parallel-groups design was used in this double-blind, placebo-controlled trial with randomization to lithium or placebo. Only those who met the aggression criterion during the 2-week placebo-baseline period were randomized to 4 weeks of treatment. Outcome measures included Clinical Global Impressions, the Global Clinical Judgements (Consensus) Scale, and the Overt Aggression Scale. RESULTS: Eighty-six inpatients enrolled in the study; 40 (33 male and 7 female; median age, 12.5 years) entered and completed the treatment phase. Lithium was statistically and clinically superior to placebo. Sixteen of 20 subjects in the lithium group were responders on the Consensus ratings vs 6 of 20 in the placebo group (P=.004). Ratings on the Overt Aggression Scale decreased significantly for the lithium group vs the placebo group (P=.04). More than half of the subjects in the lithium group experienced nausea, vomiting, and urinary frequency. CONCLUSIONS: Lithium is a safe and effective short-term treatment for aggression in inpatients with conduct disorder, although its use is associated with adverse effects.

Clinical features predictive of orbital exenteration for conjunctival melanoma.

PURPOSE: Conjunctival malignant melanoma can sometimes be difficult to control locally, and orbital exenteration may be necessary. To our knowledge, the risk factors that portend exenteration have not been previously identified. The purpose of this study was to review patients who underwent orbital exenteration for advanced disease and to identify retrospectively the clinical factors predictive of ultimate exenteration. METHODS: The records of patients with conjunctival melanoma who were managed on the Oncology Service at Wills Eye Hospital from 1974 to 1997 were reviewed. Factors predictive of orbital exenteration were analyzed using Cox proportional hazards regression models. RESULTS: Of 151 consecutive patients with conjunctival melanoma, 20 (13%) required orbital exenteration for advanced disease. The number of melanoma excisions performed before referral ranged from 0 to 11, with a mean of 2. The clinical factors predictive of orbital exenteration on multivariable analysis were visual acuity of 20/200 or worse, lack of tumor pigmentation, and extralimbal tumor location. All exenterations were performed using an eyelid-sparing technique. At mean follow-up of 51 months after exenteration, 4 patients (20%) had died of metastasis, 3 (15%) were alive with metastasis, and 13 (65%) had not developed metastasis. CONCLUSIONS: Conjunctival melanoma can show aggressive local behavior, and orbital exenteration is necessary in up to 13% of cases at a tertiary referral center. Patients with risk factors such as poor visual acuity, amelanotic tumor, and extralimbal tumor location may require wider excision and radiation therapy to control the tumor and avoid orbital exenteration. It is hoped that modern surgical approaches will decrease the need for orbital exenteration.

Combination of clinical factors predictive of growth of small choroidal melanocytic tumors.

OBJECTIVE: To better define the effect of individual risk factors and combinations thereof on the growth of small choroidal melanocytic tumors. DESIGN: Retrospective analysis. SETTING: Clinical practice of ocular oncology. PATIENTS: The study included 1287 patients with small suspicious choroidal melanocytic tumors, measuring 3 mm or less in thickness, managed with observation. RESULTS: On multivariate analysis, the clinical risk factors predictive of growth of small choroidal melanocytic tumors include tumor thickness greater than 2.0 mm, posterior tumor margin touching the disc, visual symptoms, orange pigment, and subretinal fluid. Tumor growth was detected in 4% of those patients with no risk factors. Growth was detected in approximately 36% of patients with 1 risk factor, 45% of patients with 2 risk factors, 50% of patients with 3 risk factors, 51% of patients with 4 risk factors, and 56% of patients with all 5 risk factors. The combination of risk factors offering the greatest risk for growth was tumor thickness greater than 2.0 mm, tumor margin touching disc, and subretinal fluid that was associated with tumor growth in 63% of the affected patients. The relative risk for growth was 1.9 for 1 factor, 3.8 for 2 factors, 7.4 for 3 factors, 14.1 for 4 factors, and 27.1 for all 5 risk factors combined. CONCLUSIONS: Five risk factors for growth of small choroidal melanocytic tumors have been identified. The combinations of various factors increase the risk for tumor growth from 4% if no factors are present to more than 50% if 3 or more risk factors are present. These factors may be important when counseling patients with small suspicious choroidal melanocytic tumors.

Thermotherapy for retinoblastoma.

OBJECTIVE: To evaluate the results of thermotherapy for retinoblastoma. DESIGN: Prospective, nonrandomized analysis of the treatment method. PARTICIPANTS: A total of 188 retinoblastomas in 80 eyes of 58 patients who were treated with thermotherapy. MAIN OUTCOME MEASURES: Tumor response and ocular adverse effects. RESULTS: Of 188 retinoblastomas treated with thermotherapy, mean tumor base was 3.0 mm and tumor thickness was 2.0 mm. Complete tumor regression was achieved in 161 tumors (85.6%), and 27 tumors (14.4%) developed recurrence. Using univariate analysis, the predictors of local tumor recurrence were male sex (P = .005), no color change ("no visible take") in tumor after treatment (P = .01), increasing number of treatment sessions (P = .002), and previous use of chemoreduction (P = .02). By multivariate analysis, the most important predictors of local tumor recurrence were male sex (P = .01) and previous use of chemoreduction (P = .03), the latter likely reflecting the fact that these tumors were initially larger with more ominous findings, and required chemoreduction therapy to reduce them to a size amenable to focal treatment with thermotherapy. When evaluating thermotherapy variables as a function of tumor size, it was apparent that larger tumors (> or =3.0-mm base) required greater energy and time than did smaller tumors (<3.0-mm base). Comparison of treatment variables for larger vs smaller tumors was as follows: number of treatment sessions, 3.3 vs 2.3; spot size, 1.7 vs 1.3 mm; power, 540 vs 370 mW; treatment duration, 49 vs 14 minutes; and coupling of thermotherapy with chemotherapy, 79% vs 48% of cases (P < or =.001 for each variable). Complications of thermotherapy in the 80 eyes included focal iris atrophy in 29 eyes (36%), peripheral focal lens opacity in 19 eyes (24%), retinal traction in 4 eyes (5%), retinal vascular obstruction in 2 eyes (2%), and transient localized serous retinal detachment in 2 eyes (2%). There were no cases of corneal scarring, central lens opacity, iris or retinal neovascularization, or rhegmatogenous retinal detachment. All eyes with focal lens opacity demonstrated adjacent focal iris atrophy. By multivariate analysis, the predictors of thermotherapy-induced focal iris atrophy were increasing number of treatment sessions (P = .001) and increasing tumor base (P = .02). CONCLUSIONS: Thermotherapy is used for relatively small retinoblastomas without associated vitreous or subretinal seeds. This treatment provides satisfactory control for selected retinoblastomas, with 86% of tumors demonstrating lasting regression. Tumors that measure 3.0 mm or larger in base at the time of thermotherapy require more intense treatment than smaller tumors and are at greatest risk for ocular complications such as focal iris atrophy and focal paraxial lens opacity.

Advising parents of asthmatic children on passive smoking: randomised controlled trial.

OBJECTIVE: To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke. DESIGN: Randomised controlled trial. SETTING: Tayside and Fife, Scotland. PARTICIPANTS: 501 families with an asthmatic child aged 2-12 years living with a parent who smoked. INTERVENTION: Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child's health. MAIN OUTCOME MEASURES: Salivary cotinine concentrations in children, and changes in reported smoking habits of the parents 1 year after the intervention. RESULTS: At the second visit, about 1 year after the baseline visit, a small decrease in salivary cotinine concentrations was found in both groups of children: the mean decrease in the intervention group (0.70 ng/ml) was slightly smaller than that of the control group (0.88 ng/ml), but the net difference of 0.19 ng/ml had a wide 95% confidence interval (-0.86 to 0.48). Overall, 98% of parents in both groups still smoked at follow up. However, there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking. CONCLUSIONS: A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children's exposure to environmental tobacco smoke. The intervention may have made some parents less inclined to stop smoking. If a clinician believes that a child's health is being affected by parental smoking, the parent's smoking needs to be addressed as a separate issue from the child's health.

Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma.

OBJECTIVE: To identify the risk factors that lead to the development of radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Radiation retinopathy is a slowly progressive, occlusive vasculopathy characterized by radiation-induced endothelial damage. METHODS: Review of the medical records of patients with posterior uveal melanoma treated with plaque radiotherapy. RESULTS: Of 1300 patients with posterior uveal melanoma treated with plaque radiotherapy from July 1, 1976, through June 30, 1992, radiation retinopathy developed in 560 (43.1%). By using Kaplan-Meier survival estimates, we found that 5% of the patients had nonproliferative radiation retinopathy at 1 year (95% confidence interval [CI], 3%-6%) and 42% at 5 years (95% CI, 38%-45%). The proportion of patients with proliferative retinopathy was 1% at 1 year (95% CI, 0.2%-1.5%) and 8% at 5 years (95% CI, 5%-10%). Multivariate analyses showed that the subset of clinical variables best related to the development of nonproliferative radiation retinopathy were tumor margin of less than 4 mm from foveola (P<.001), tumor limited to the choroid (P = .002), and radiation dose rate of greater than 260 cGy/h to the tumor base (P = .02). The best subset of independent variables related to the development of radiation maculopathy were tumor of less than 4 mm to foveola (P<.001) and the use of radioisotope iridium 192 (192Ir) (P = .02) compared with iodine 125 (125I). From a multivariate model, the most important factors for the development of proliferative radiation retinopathy included diabetes mellitus (P = .01), radioisotope 192Ir (P = .01) compared with 125I, and tumor base of greater than 10 mm (P = .02). CONCLUSIONS: Radiation retinopathy is a common finding after plaque radiotherapy for choroidal melanoma, occurring in 42% of patients at 5 years. The main predictors of radiation retinopathy are posterior tumor location with margin near the foveola and high radiation dose rate to the tumor base.