The impact of age and gender on papillary thyroid cancer survival.

CONTEXT: Thyroid cancer predominately affects women, carries a worse prognosis in older age, and may have higher mortality in men. Superimposed on these observations is the fact that most women have attained menopause by age 55 yr. OBJECTIVE: The objective of the study was to determine whether men contribute disproportionately to papillary thyroid cancer (PTC) mortality or whether menopause affects PTC prognosis. DESIGN: Gender-specific mortality was normalized using age-matched subjects from the U.S. population. Multivariate Cox proportional hazard regression models incorporating gender, age, and National Thyroid Cancer Treatment Cooperative Study Group stage were used to model disease-specific survival (DSS). PARTICIPANTS AND SETTING: Patients were followed in a prospective registry. MAIN OUTCOME MEASURE: The relationships between gender, age, and PTC outcomes were analyzed. RESULTS: The unadjusted hazard ratio (HR) for DSS for women was 0.40 [confidence interval (CI) 0.24-0.65]. This female advantage diminished when DSS was adjusted for age at diagnosis and stage with a HR encompassing unity (HR 0.72, CI 0.44-1.19). Additional multivariate models of DSS considering gender, disease stage, and various age groupings showed that the DSS for women diagnosed at under 55 yr was improved over men (HR 0.33, CI 0.13-0.81). However, the HR for DSS increased to become similar to men for women diagnosed at 55-69 yr (HR 1.01, CI 0.42-2.37) and at 70 yr or greater (HR 1.17, CI 0.48-2.85). CONCLUSIONS: Although the overall outcome of women with PTC is similar to men, subgroup analysis showed that this composite outcome is composed of two periods with different outcomes. The first period is a period with better outcomes for women than men when the diagnosis occurs at younger than 55 yr; the second is a period with similar outcomes for both women and men diagnosed at ages greater than 55 yr. These data raise the question of whether an older age cutoff would improve current staging systems. We hypothesize that older age modifies the effect of gender on outcomes due to menopause-associated hormonal alterations.

Outcomes of patients with differentiated thyroid carcinoma following initial therapy.

This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients.

Selected therapy-related clinical research topics in osteoporosis.

Effective antiresorptive treatment options are currently available for fracture prevention in patients with osteopenia and osteoporosis. Although orally administered bisphosphonates are most widely used, they demonstrate specific compliance requirements and potential side effects. Medical therapy targeting acute fractures is lacking. This paper reviews two recently published studies. The first readdresses the use of intravenous bisphosphonates as a primary choice for fracture prevention; it concludes that once yearly administration may be a practical option. The second study assesses the effects of short-term use of a subcutaneous infusion of insulin-like growth factor (IGF)-I bound to its primary binding protein, IGFBP-3, on blunting the catabolic events associated with hip fractures. The investigators suggest that this intervention merits additional evaluation as a potentially important modality to improve care in this patient population.

Paying doctors more: use of musculoskeletal specialists and increased physician pay to decrease workers' compensation costs.

Previous studies evaluating workers' compensation care systems used retrospective controls. We performed a concurrent effectiveness study comparing a WC system that used visiting musculoskeletal specialists to assist primary care physicians with a typical discounted-fee, WC, managed-care system. In the new specialist-direct system, physicians could not profit from self-referral, but were paid 35% to 69% more per patient visit than doctors in the discounted-fee clinics. All claims filed by all employees of two hotels for 2 years were examined. Patients had self-selected either a specialist-direct or a discounted-fee clinic, and the entire cost of the claim was assigned to either system of care. Claim costs were 63% lower in the specialist-direct system (P < 0.001). Medical costs were 45% less (P < 0.014), and indemnity 85% less (P < 0.001), in this system. Claims were closed nearly 6 months faster in the specialist-direct system (P < 0.0001). Indemnity claims were more common in the discounted-fee system (P < 0.0001). Claimant and injury characteristics were not significantly different between the systems. This new care model is a cost-effective alternative to discounted WC managed care. Discounting the services of the primary treating physician may result only in cost-shifting, not cost-saving.

Back pain, the uncomfortable truth - assurance and activity problem.

Back problems are common, expensive, and the few patients who are the crux of the problem are uncomfortable but also an uncomfortable frustration for clinicians and employers alike. We now know that clinicians can greatly improve the patient's response to back symptoms by admitting our diagnostic limitations, demedicalizing the issue, providing assurance, and encouraging a more reasonable approach to improving comfortable activity tolerance.

American Thyroid Association guidelines for detection of thyroid dysfunction.

OBJECTIVE: To define the optimal approach to identify patients with thyroid dysfunction. PARTICIPANTS: The 8-member Standards of Care Committee of the American Thyroid Association prepared a draft, which was reviewed by the association's 780 members, 50 of whom responded with suggested revisions. EVIDENCE: Relevant published studies were identified through MEDLINE and the association membership's personal resources. CONSENSUS PROCESS: Consensus was reached at group meetings. The first draft was prepared by a single author (P.W.L.) after group discussion. Suggested revisions were incorporated after consideration by the committee. CONCLUSIONS: The American Thyroid Association recommends that adults be screened for thyroid dysfunction by measurement of the serum thyrotropin concentration, beginning at age 35 years and every 5 years thereafter. The indication for screening is particularly compelling in women, but it can also be justified in men as a relatively cost-effective measure in the context of the periodic health examination. Individuals with symptoms and signs potentially attributable to thyroid dysfunction and those with risk factors for its development may require more frequent serum thyrotropin testing.

Perils, pitfalls, and accomplishments of guidelines for treatment of back problems.

Science should be the basis for guidelines. As a result of the Flexner Report in 1911, we now live in an era where randomized trials are available. Statistical methods can truly be applied to evaluate the reliability of data published in the literature. The result is that we can now demand more from future publications and allow for a better evaluation of the mistakes or bias that can distort validity, applicability, and reliability. The importance of this methodology is to reduce misunderstandings by patients, clinicians, manufacturers, and government agencies about issues important to patient care.

Outcome after treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma. DESIGN: Analysis of data from a multicenter study. SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). MEASUREMENTS: Death, disease progression, and disease-free survival. RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.

Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry.

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.

Prospective multicenter study of thyroiscarcinoma treatment: initial analysis of staging and outcome. National Thyroid Cancer Treatment Cooperative Study Registry Group.

BACKGROUND: A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with other available staging classifications. METHODS: Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation. RESULTS: Between 1987 and 1995, 1607 patients were registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were more likely to have "high risk" Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. Five-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage IV (P < 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1%for Stage II, 77.8% for Stage III, and 24.6% for Stage IV). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type. CONCLUSIONS: The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma.

Scientific application of sports medicine principles for acute low back problems. The Agency for Health Care Policy and Research Low Back Guideline Panel (AHCPR, Guideline #14)

The Agency for Health Care Policy and Research Low Back Guideline Panel (AHCPR, Guideline #14) truly brought to life sports medicine principles in the care of the most common and expensive musculoskeletal problem by focusing on the basic activity paradigm of musculoskeletal limitations. Twenty-three experts and seven international consultants led a review of over 10,000 abstracts and evaluation of over 4,600 articles. This effort was to establish scientifically how any clinician can: 1) safely be sure that the patient only has a back problem, 2) offer safe options for comfort, and 3) concentrate on the real treatment for an activity intolerance with sports medicine principles: activity, not rest, begets activity tolerance. Evidence tables and their subsequent derivation as "Finding and Recommendation Statements" provide an understanding of what medical science can and cannot presently support as predictable.

Three-dimensional head kinematics and cervical range of motion in the diagnosis of patients with neck trauma.

OBJECTIVE: To create a statistical model using three-dimensional (3D) head kinematics and range of motion (ROM) to distinguish between people with whiplash syndrome and asymptomatic controls. STUDY DESIGN: Cross-sectional study to estimate validity of diagnostic measures. METHODS: Fifty-one asymptomatic controls (most of whom were women), 18-35 yr old and 30 matched whiplash trauma patients seeking care from suburban outpatient clinics were sought. 3D kinematic parameters of head motion were obtained during tracking tasks (e.g., flexion, extension, etc.) and cervical ROM was measured via a head mounted inclinometer. Their level of pain and disability was assessed via a self-administered neck disability index questionnaire and visual analog pain scale (VAS). RESULTS: A scoring system of biomechanical abnormalities derived from the vertical piercing point, its second derivative and symmetry during oblique tasks. The scores ranged from a minimum of 0 to a maximum of 3. A cutoff of > or = 0.5 correctly identified the greatest number of subjects and minimized false positives (sensitivity 77%, specificity 82%, likelihood ratio 4.5). ROM performed similarly well at a cutoff of 1 SD below the normative mean (sensitivity 77%, specificity 84%, likelihood ratio 3.9). CONCLUSIONS: There is potential for biomechanical analysis to objectively detect abnormalities. The statistical model yielded moderate to high sensitivity and specificity using 3D helical-axis parameters of the head and standard ROM. The model development will continue via this process in future studies. These data could be a first step toward the creation of useful, noninvasive protocols for the diagnosis and management of soft tissue trauma of the neck.

Characteristics in Medicare beneficiaries associated with reoperation after lumbar spine surgery.

STUDY DESIGN: A cohort study was undertaken using medical claims of Medicare beneficiaries. OBJECTIVES: Factors associated with reoperation after lumbar spine surgery were identified. SUMMARY OF BACKGROUND DATA: Repeat spine surgery is one outcome measure of surgical success, but little is known about clinical or demographic factors associated with repeat surgery. METHODS: Medicare beneficiaries who had surgery in 1985 were included in follow-up through 1989. Time between the first operation and a lumbar spine reoperation, death, or end of follow-up period was recorded. Survival analysis (time-to-event) techniques were used to test the association of baseline characteristics with reoperation. RESULTS: Higher reoperation rates were associated (P < 0.05) with previous back surgery, younger age, recent hospitalization, white race, and diagnosis of herniated disc (compared with other diagnoses). Fusion alone or combined with other procedures did not lower the reoperation rate. CONCLUSION: Reoperation rates are affected not only by technical factors, but also by demographic and clinical characteristics that are often omitted from reports of surgical case series.

B-scan ultrasonic measurement of the lumbar spinal canal as a predictor of industrial back pain complaints and extended work loss.

B-scan ultrasonic measurements of lumbar spinal canal diameter were examined as predictors of industrial back pain complaints and extended work loss. Baseline data were collected on 3,020 Washington State aircraft manufacturing workers, and over a mean 3.7-year follow-up period 352 subjects reported industrial back pain complaints. Mean canal measurements of subjects with industrial back pain complaints were smaller at all spinal levels than in subjects without complaints. The mean differences between the groups, however, were extremely small (0.07 mm to 0.51 mm), and not all levels were statistically significant. The relative risk for an L5-S1 measurement 2 standard deviations below the mean was 1.4, yet the measurement explained less than 1% of the uncertainty in predicting complaints. No association was found between canal measurements and claims with extended work loss of greater than one month. The imprecision of the measurements and poor predictive ability indicate that B-scan ultrasonography, as used in this study, is of dubious screening value.

Lumbar spinal fusion. A cohort study of complications, reoperations, and resource use in the Medicare population.

Regional variations in lumbar spinal fusion rates suggest a poor consensus on surgical indications. Therefore, complications, costs, and reoperation rates were compared for elderly patients undergoing surgery with or without spinal fusion. Subjects were Medicare recipients who underwent surgery in 1985, with 4 years of subsequent follow-up. There were 27,111 eligible patients, of whom 5.6% had fusions. Mean age was 72 years. Patients undergoing fusion had a complication rate 1.9 times greater than those who had surgery without fusion. The blood transfusion rate was 5.8 times greater, nursing home placement rate 2.2 times greater, and hospital charges 1.5 times higher (all P < 0.0005). Six-week mortality was 2.0 times greater for patients undergoing fusions (P = 0.025). Reoperation rates at 4 years were no lower for patients who had fusion surgery and results were similar in most diagnostic subgroups. Indications for fusion among older patients require better definition, preferably based on outcomes from prospective controlled studies.

Serum growth hormone response to growth hormone-releasing hormone in non-obese and obese adults with hypopituitarism.

The clinical consequences of growth hormone (GH) deficiency (GHD) in adults have not been defined. Standard methods of measuring GH reserve in children may not be reliable in adults. In addition, obesity in normal adults diminishes GH responsiveness to provocative stimuli; this inhibition of GH release is reversed with pyridostigmine (PD). We investigated the use of GH-releasing hormone (GHRH) as a method to assess pituitary GH secretory reserve (as defined by peak GH response to GHRH) in both non-obese and obese (ie, > 115% ideal body mass index [BMI]) adults with hypothalamic-pituitary tumors. Nine non-obese patients (NOP) and 10 obese patients (OP) were studied with 11 non-obese controls (NOC) and 10 obese controls (OC). All study groups received GHRH (1 microgram/kg intravenous bolus) with blood sampling at -15, 0, 15, 30, 45, 60, 75, and 90 minutes. OC and OP received 120 mg PD orally 1 hour before GHRH injection. Mean serum GH responses in NOC and OC were significantly higher (P < .05) than those in NOP and OP, respectively, 15 minutes after GHRH injection, and remained so throughout the time-course of the test. Mean +/- standard error of the mean (SEM) peak GH level (microgram/L) was lower in NOP than in NOC (5.1 +/- 1.6 v 21.2 +/- 4.4, P < .01) and lower in OP than in OC (4.6 +/- 1.8 v 15.5 +/- 2.2, P < .01). Mean +/- SEM peak GH level was also lower in NOP than in OC (5.1 +/- 1.6 v 15.5 +/- 2.2 micrograms/L, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Differential changes in serum concentrations of androgens and estrogens (in relation with cortisol) in postmenopausal women with acute illness.

Previous studies of adrenal androgens and estrogens in critical illness were limited by measuring only selected sex steroids and by including men (who have confounding simultaneous changes in gonadal steroids). We evaluated relationships between changes in serum levels of cortisol (F), androgens, estrogens, and gonadotropins in 20 postmenopausal women with acute critical illness to determine if changes in adrenal androgens and estrogens paralleled gonadal axis suppression or adrenal stimulation. Two patterns of changes in sex steroids were observed. Admission serum levels of androstenedione (delta 4-A), estradiol, and estrone, like F, were increased compared to healthy controls (P < 0.0001). delta 4-A and estrone then decreased toward normal by day 5 in parallel with cortisol (r = 0.56 and 0.60). In contrast, admission serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were not elevated and testosterone (T) was decreased in our patients compared to controls (P < 0.0005) in parallel with serum gonadotropin levels. Serum levels of DHEA and T continued to decrease by day 5 in parallel with gonadotropins. We conclude that in agonadal patients with acute critical illness, serum levels of DHEA-S and T are selectively decreased in relation to F, delta 4-A, and estrogens. The decreased serum T levels suggest inhibition of 17 beta-OH-dehydrogenase and/or increased aromatization to estradiol. The marked increase in serum estrogen levels also suggests increased aromatization. The absence of increases in DHEA and DHEA-S suggest enhanced activity of 3 beta-hydroxysteroid dehydrogenase and/or inhibition of C17,20-lyase activity of P-450c17. The clinical significance of this marked increase in the ratio of estrogens to androgens in acute illness requires further investigation.