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Biomedical subjects

Clyde B Schechter

Publications and source records attributed to Clyde B Schechter.

12 recordsLinked to original sources

Lipoprotein genotype and conserved pathway for exceptional longevity in humans.

Alteration of single genes involved in nutrient and lipoprotein metabolism increases longevity in several animal models. Because exceptional longevity in humans is familial, it is likely that polymorphisms in genes favorably influence certain phenotypes and increase the likelihood of exceptional longevity. A group of Ashkenazi Jewish centenarians (n = 213), their offspring (n = 216), and an age-matched Ashkenazi control group (n = 258) were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease (CVD). These genes were tested for association with serum lipoprotein levels and particle sizes, apolipoprotein A1, B, and C-3 levels and with outcomes of hypertension, insulin resistance, and mortality. The prevalence of homozygosity for the -641C allele in the APOC3 promoter (rs2542052) was higher in centenarians (25%) and their offspring (20%) than in controls (10%) (p = 0.0001 and p = 0.001, respectively). This genotype was associated with significantly lower serum levels of APOC3 and a favorable pattern of lipoprotein levels and sizes. We found a lower prevalence of hypertension and greater insulin sensitivity in the -641C homozygotes, suggesting a protective effect against CVD and the metabolic syndrome. Finally, in a prospectively studied cohort, a significant survival advantage was demonstrated in those with the favorable -641C homozygote (p < 0.0001). Homozygosity for the APOC3 -641C allele is associated with a favorable lipoprotein profile, cardiovascular health, insulin sensitivity, and longevity. Because modulation of lipoproteins is also seen in genetically altered longevity models, it may be a common pathway influencing lifespan from nematodes to humans.

Aged↗

Mental retardation and prenatal methylmercury toxicity.

BACKGROUND: Methylmercury (MeHg) is a developmental neurotoxicant; exposure results principally from consumption of seafood contaminated by mercury (Hg). In this analysis, the burden of mental retardation (MR) associated with methylmercury exposure in the 2000 U.S. birth cohort is estimated, and the portion of this burden attributable to mercury (Hg) emissions from coal-fired power plants is identified. METHODS: The aggregate loss in cognition associated with MeHg exposure in the 2000 U.S. birth cohort was estimated using two previously published dose-response models that relate increases in cord blood Hg concentrations with decrements in IQ. MeHg exposure was assumed not to be correlated with native cognitive ability. Previously published estimates were used to estimate economic costs of MR caused by MeHg. RESULTS: Downward shifts in IQ resulting from prenatal exposure to MeHg of anthropogenic origin are associated with 1,566 excess cases of MR annually (range: 376-14,293). This represents 3.2% of MR cases in the US (range: 0.8%-29.2%). The MR costs associated with decreases in IQ in these children amount to $2.0 billion/year (range: $0.5-17.9 billion). Hg from American power plants accounts for 231 of the excess MR cases/year (range: 28-2,109), or 0.5% (range: 0.06%-4.3%) of all MR. These cases cost $289 million (range: $35 million-2.6 billion). CONCLUSIONS: Toxic injury to the fetal brain caused by Hg emitted from coal-fired power plants exacts a significant human and economic toll on American children.

Cohort Studies↗

Predictors of timely initiation of gynecologic care among urban adolescent girls.

PURPOSE: To determine whether or not critical sexual health services are delivered to low-income girls, and to identify predictors of timely initiation of gynecologic care for sexually active adolescent girls. Few studies have addressed the interval between sexual debut and risk-appropriate primary care services. METHODS: We conducted an anonymous, cross-sectional, laptop-based, self-administered branching survey of 9th-12th grade girls in three Bronx public high schools (n = 819). RESULTS: Over half (60.0%) had an opportunity for confidential care at last clinical visit. Only 27% of sexually active girls had informed any clinician that they had been sexually active; 45% had ever had a pelvic exam. The mean interval between sexual debut and initial pelvic exam (our proxy for gynecologic care) was 13.3 months (range = 0-70 months, SD = 11.8 months). Cox proportional hazard modeling identified four predictors of time to first pelvic exam: experience of sexually transmitted infection (STI) or pregnancy (hazard ratio [HR] = 1.9), having disclosed sexual activity to any clinician (HR = 1.7), access to confidential care (HR = 3.1), and high self-efficacy for accessing confidential care (HR = 2.1). CONCLUSIONS: Most sexually active girls have not told a clinician that they are sexually active and many have not had counseling related to sexual health. Delay between sexual debut and initial pelvic exam is substantial for low-income urban girls, and often occurs in reaction to pregnancy or STI. Setting of usual care does not predict timely gynecologic care, but access to confidential care does.

Adolescent↗

The SPECTRUM population model of the impact of screening and treatment on U.S. breast cancer trends from 1975 to 2000: principles and practice of the model methods.

OBJECTIVE: This stochastic simulation model was developed to estimate the impact of screening and treatment diffusion on U.S. breast cancer mortality between 1975 and 2000. MODELING APPROACH: We use an event-driven continuous-time state transition model. Women who are destined to develop breast cancer may be screen detected, present with symptoms, or die of other causes before cancer is diagnosed. At presentation, the cancer has a stage assigned on the basis of mode of detection. Cancers are assumed to be estrogen receptor (ER) positive or negative. Data on screening and treatment diffusion are based on national datasets; other parameters are based on a synthesis of the evidence available in the literature. MODEL METHODS: The model is calibrated to predict incidence and stage distribution (in situ, local, regional, and distant). Other than screening or treatment, background events that affect mortality are not explicitly modeled but are captured in the deviation between model projections of mortality trends and actual trends. We assume that: 1) tumors progress more slowly in older age groups, 2) screen- and clinically detected disease have the same survival conditional on age and stage, 3) women do not die of breast cancer within the "lead time" period, 4) screening benefits are captured by shifts in stage at diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical sojourn time and dwell times in each of the clinical stages are stochastically independent. MODEL RESULTS: Dissemination of screening and therapeutic advances had a substantial impact on mortality trends. We estimate that, by the year 2000, diffusion of screening lowered mortality by 12.4% and treatment improvements and dissemination lowered mortality by 14.6%. CONCLUSIONS: Models such as this one can be useful to translate clinical trial findings to general populations. This model can also be used inform policy debates about how to best achieve targeted reductions in breast cancer morbidity and mortality.

Adult↗

Toward optimal screening strategies for older women. Costs, benefits, and harms of breast cancer screening by age, biology, and health status.

CONTEXT: Optimal ages of breast cancer screening cessation remain uncertain. OBJECTIVE: To evaluate screening policies based on age and quartiles of life expectancy (LE). DESIGN AND POPULATION: We used a stochastic model with proxies of age-dependent biology to evaluate the incremental U.S. societal costs and benefits of biennial screening from age 50 until age 70, 79, or lifetime. MAIN OUTCOME MEASURES: Discounted incremental costs per life years saved (LYS). RESULTS: Lifetime screening is expensive (151,434 dollars per LYS) if women have treatment and survival comparable to clinical trials (idealized); stopping at age 79 costs 82,063 dollars per LYS. This latter result corresponds to costs associated with an LE of 9.5 years at age 79, a value expected for 75% of 79-year-olds, about 50% of 80-year-olds, and 25% of 85-year-olds. Using actual treatment and survival patterns, screening benefits are greater, and lifetime screening of all women might be considered (114,905 dollars per LYS), especially for women in the top 25% of LE for their age (50,643 dollars per LYS, life expectancy of approximately 7 years at age 90). CONCLUSIONS: If all women receive idealized treatment, the benefits of mammography beyond age 79 are too low relative to their costs to justify continued screening. However, if treatment is not ideal, extending screening beyond age 79 could be considered, especially for women in the top 25% of life expectancy for their age.

Age Factors↗

Benefits and costs of interventions to improve breast cancer outcomes in African American women.

PURPOSE: Historically, African American women have experienced higher breast cancer mortality than white women, despite lower incidence. Our objective was to evaluate whether costs of increasing rates of screening or application of intensive treatment will be off-set by survival benefits for African American women. METHODS: We use a stochastic simulation model of the natural history of breast cancer to evaluate the incremental societal costs and benefits of status quo versus targeted biennial screening or treatment improvements among African Americans 40 years of age and older. Main outcome measures were number of mammograms, stage, all-cause mortality, and discounted costs per life year saved (LYS). RESULTS: At the current screening rate of 76%, there is little incremental benefit associated with further increasing screening, and the costs are high: 124,053 US dollars and 124,217 US dollars per LYS for lay health worker and patient reminder interventions, respectively, compared with the status quo. Using reminders would cost 51,537 US dollars per LYS if targeted to virtually unscreened women or 78,130 US dollars per LYS if targeted to women with a two-fold increase in baseline risk. If all patients received the most intensive treatment recommended, costs increase but deaths decrease, for a cost of 52,678 US dollars per LYS. Investments of up to 6,000 US dollars per breast cancer patient could be used to enhance treatment and still yield cost-effectiveness ratios of less than 75,000 US dollars per LYS. CONCLUSION: Except in pockets of unscreened or high-risk women, further investments in interventions to increase screening are unlikely to be an efficient use of resources. Ensuring that African American women receive intensive treatment seems to be the most cost-effective approach to decreasing the disproportionate mortality experienced by this population.

Adult↗

Environmental pollutants and disease in American children: estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities.

In this study, we aimed to estimate the contribution of environmental pollutants to the incidence, prevalence, mortality, and costs of pediatric disease in American children. We examined four categories of illness: lead poisoning, asthma, cancer, and neurobehavioral disorders. To estimate the proportion of each attributable to toxins in the environment, we used an environmentally attributable fraction (EAF) model. EAFs for lead poisoning, asthma, and cancer were developed by panels of experts through a Delphi process, whereas that for neurobehavioral disorders was based on data from the National Academy of Sciences. We define environmental pollutants as toxic chemicals of human origin in air, food, water, and communities. To develop estimates of costs, we relied on data from the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, National Center for Health Statistics, the Bureau of Labor Statistics, the Health Care Financing Agency, and the Practice Management Information Corporation. EAFs were judged to be 100% for lead poisoning, 30% for asthma (range, 10-35%), 5% for cancer (range, 2-10%), and 10% for neurobehavioral disorders (range, 5-20%). Total annual costs are estimated to be $54.9 billion (range $48.8-64.8 billion): $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders. This sum amounts to 2.8 percent of total U.S. health care costs. This estimate is likely low because it considers only four categories of illness, incorporates conservative assumptions, ignores costs of pain and suffering, and does not include late complications for which etiologic associations are poorly quantified. The costs of pediatric environmental disease are high, in contrast with the limited resources directed to research, tracking, and prevention.

Asthma↗

Is HIV infection a risk factor for complications of surgery?

BACKGROUND: The literature is inconsistent as to whether HIV-infected patients have higher rates of surgical complication rates than HIV-uninfected patients. This inconsistency reflects the failure to control for confounding variables in many of the previous studies. METHODS: A retrospective cohort study of records of HIV-infected individuals who underwent surgical procedures between 1990 and 1995 was matched with the records of HIV-uninfected control patients. We performed a logistic regression analysis to determine the independent effects of HIV infection and other potential risk factors for surgical complications. RESULTS: The crude rates of death and infectious and hematologic complications were higher among HIV-infected patients than among uninfected patients. Although the crude risk of having any complication was higher among the HIV-infected (odds ratio [OR]=2.47, p=0.015), the adjusted risk was not (OR=0.72 [p<0.613]). Variables significantly associated with complications were American Society of Anesthesiology (ASA) risk class (OR=2.7), age (OR=1.06 per year), and weight (OR=0.96 per kg). CONCLUSIONS: HIV sero-status was not found to be an independent risk factor for complications of surgery. The most important risk factor for complication of surgery in HIV-infected patients is ASA risk class.

Adult↗

Provider evaluation of a multifaceted system of care to improve recognition and management of pregnant women experiencing domestic violence.

This article describes the provider evaluation of a multifaceted system of care for pregnant women experiencing domestic violence and who receive prenatal care in an urban family practice site, one of four national demonstration projects. Providers reported changes in their own self-efficacy and behavior, but showed little improvement in overall attitudes or knowledge. Focus groups revealed that an easily accessible domestic violence coordinator was important, whereas providers stated that most domestic violence protocol materials were not useful. Guidelines that rely on training and protocols have had limited national success, suggesting that additional systems of care such as written chart prompts, quality improvement, and on-site domestic violence services may be necessary. This intervention was well received by providers, a key factor in any effort to alter provider behavior.

Adult↗

Posterior progress.

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Bayes Theorem↗

Mediating medical malpractice lawsuits against hospitals: New York City's Pilot Project.

The New York City Health and Hospitals Corporation participated in a feasibility study to measure the participants' satisfaction with mediation of medical malpractice lawsuits. Twenty-nine cases were referred to the study, twenty-four agreed to mediation, and nineteen were mediated. Satisfaction data indicate that the plaintiffs and their attorneys and the defendant's attorney were satisfied with the process whether or not settlement was reached. The mean length of a mediation was 2.34 hours. Of the cases mediated, thirteen settled, with a median payment of 111,000 dollars. The defendant's and plaintiffs' attorneys estimated spending approximately one-tenth the amount of time preparing their case for mediation that they would have spent preparing for trial.

Attitude↗