Background The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. Methods We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. Results At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 perce...

Environmental and Heritable Factors in the Causation of Cancer — Analyses of Cohorts of Twins from Sweden, Denmark, and Finland

The past decade has seen substantial research on exact infer- ence for contingency tables, both in terms of developing new analyses and developing efficient algorithms for computations. Coupled with concomitant improvements in computer power, this research has re- sulted in a greater variety of exact procedures becoming feasible for practical use and a considerable increase in the size of data sets to which the procedures can be applied. For some basic analyses of contin- gency tables, it is unnecessary to use large-sample approximations to sampling distributions when their adequacy is in doubt. This article surveys the current theoretical and computational developments of exact methods for contingency tables. Primary attention is given to the exact conditional approach, which eliminates nuisance parameters by conditioning on their sufficient statistics. The presentation of various exact inferences is unified by expressing them in terms of parameters and their sufficient statistics in loglinear models. Exact approaches for many inferences are not yet addressed in the literature, particularly for multidimensional contingency tables, and this article also suggests additional research for the next decade that would make exact methods yet more widely applicable.

https://projecteuclid.org/download/pdf_1/euclid.ss/1177011454

A Survey of Exact Inference for Contingency Tables

BACKGROUND: Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. METHODS: Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. RESULTS: Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. CONCLUSIONS: Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.

Cinacalcet for Secondary Hyperparathyroidism in Patients Receiving Hemodialysis

Background There is substantial evidence that antidepressant medications treat moderate to severe depression effectively, but there is less data on cognitive therapy’s effects in this population. Objective To compare the efficacy in moderate to severe depression of antidepressant medications with cognitive therapy in a placebo-controlled trial. Design Random assignment to one of the following: 16 weeks of medications (n = 120), 16 weeks of cognitive therapy (n = 60), or 8 weeks of pill placebo (n = 60). Setting Research clinics at the University of Pennsylvania, Philadelphia, and Vanderbilt University, Nashville, Tenn. Patients Two hundred forty outpatients, aged 18 to 70 years, with moderate to severe major depressive disorder. Interventions Some study subjects received paroxetine, up to 50 mg daily, augmented by lithium carbonate or desipramine hydrochloride if necessary; others received individual cognitive therapy. Main Outcome Measure The Hamilton Depression Rating Scale provided continuous severity scores and allowed for designations of response and remission. Results At 8 weeks, response rates in medications (50%) and cognitive therapy (43%) groups were both superior to the placebo (25%) group. Analyses based on continuous scores at 8 weeks indicated an advantage for each of the active treatments over placebo, each with a medium effect size. The advantage was significant for medication relative to placebo, and at the level of a nonsignificant trend for cognitive therapy relative to placebo. At 16 weeks, response rates were 58% in each of the active conditions; remission rates were 46% for medication, 40% for cognitive therapy. Follow-up tests of a site × treatment interaction indicated a significant difference only at Vanderbilt University, where medications were superior to cognitive therapy. Site differences in patient characteristics and in the relative experience levels of the cognitive therapists each appear to have contributed to this interaction. Conclusion Cognitive therapy can be as effective as medications for the initial treatment of moderate to severe major depression, but this degree of effectiveness may depend on a high level of therapist experience or expertise.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/208460/yoa30320.pdf

Cognitive therapy vs medications in the treatment of moderate to severe depression.

Over a 6-month period, 23 members of the International Microvascular Research Group participated in a prospective survey of their microvascular free-flap practice. Data were recorded with each case for 60 variables covering patient characteristics, surgical technique, pharmacologic treatment, and postoperative outcome. A total of 493 free flaps were reported with a representative demographic distribution for age, sex, indications for surgery, risk factors, flap type, surgical technique, and pharmacologic intervention. Mixed effects logistic regression modeling was used to determine predictors of flap failure and associated complications. The overall incidence of flap failure was 4.1 percent (20 of 493). Reconstruction of an irradiated recipient site and the use of a skin-grafted muscle flap were the only statistically significant predictors of flap failure, with increased odds of failure of 4.2 (p = 0.01) and 11.1 (p = 0.03), respectively. A postoperative thrombosis requiring re-exploration surgery occurred in 9.9 percent of the flaps. The incidence of this complication was significantly higher when the flap was transferred to a chronic wound and when vein grafts were needed, with increased odds of failure of 2.9 (p = 0.02) and 2.5 (p = 0.02), respectively. There was a lower incidence of postoperative thrombosis when rectus/transverse rectus abdominis muscle (TRAM) flaps were used, where odds of failure decreased by 0.36 (p = 0.04), and when subcutaneous heparin was administered in the postoperative period, where odds decreased by 0.27 (p = 0.04). There was an overall 69-percent salvage rate for flaps identified with a postoperative thrombosis. Intraoperative thrombosis occurred in 41 cases (8.3 percent) and was observed more frequently in myocutaneous flaps or when vein grafts were needed (5.5 and 5.0 greater odds, respectively; p < 0.001) but was not associated with higher flap failure (2 of 41 cases; 4.9-percent failure rate). The incidence of a hematoma and/or hemorrhage was increased in obese patients and when vein grafts were needed [2.7 (p = 0.02) and 2.6 (p = 0.03) greater odds, respectively], whereas this complication was significantly decreased in muscle flaps (myocutaneous or skin-grafted muscle), in tobacco users, when a heparinized solution was used for general wound irrigation, and when the attending surgeon performed the arterial anastomosis (in contrast to the resident or fellow on staff) (p < 0.05 for each factor). With the multivariable analysis, many factors were found not to have a significant effect on flap outcome, including the recipient site (e.g., head/neck, breast, lower limb, etc.); indications for surgery (trauma, cancer, etc.); flap transfer in extremes of age, smokers, or diabetics; arterial anastomosis with an end-to-end versus end-to-side technique; irrigation of the vessel without or with heparin added to the irrigation solution; and a wide spectrum of antithrombotic drug therapies. These results present a current baseline for free-flap surgery to which future advances and improvements in technique and practice may be compared.

A Prospective Study of Microvascular Free-Flap Surgery and Outcome

Many health research investigations are concerned with the relationship be­ tween a primary factor, such as a potentially harmful exposure, a new therapy, or an intervention, and a response variable such as disease status, level of functioning, or extent of improvement. Quite frequently, both of these variables are reported on categorical measurement scales, either nomi­ nal or ordinal , so that the reSUlting data can be displayed as observed frequencies in a two-way contingency table. However, this factor-response relationship also may be influenced by additional variables, typically referred to as intervening variables, confounding variables, effect modifiers, or covariables, because of their effects on the response variable and its relation­ ship with the primary factor. For example, the study may be conducted at several institutions involving different investigators and patient popUlations;

https://www.annualreviews.org/doi/pdf/10.1146/annurev.pu.09.050188.001011

A General Overview of Mantel-Haenszel Methods: Applications and Recent Developments

We propose an alternative method to obtain summary estimators, variances and confidence intervals for attributable risk measures This method combines weighted exposure prevalences for cases and controls across strata formed by the cross-classification of relevant covariates to form estimates of attributable risk among the exposed and attributable risk in the target population The major benefit of this approach over those previously proposed in the literature is that it operates on data summed across strata rather than on estimation of statistics within each stratum This alternative method for attributable risk measures utilizes the Mantel-Haenszel estimate of an average odds ratio, and can be implemented using the matrix procedure in SAS This method is appropriate even when the within-stratum sample sizes are too small for other methods to be valid Simulation results indicate that this method is superior to others with respect to bias and coverage probability for confidence intervals

Summary attributable risk estimation from unmatched case‐control data

This article provides an overview of generalized Mantel–Haenszel (MH) methods for the analysis of categorical data from factor–response and repeated measures study designs. These methods are illustrated using data from two different clinical research studies, investigating treatment differences within several different sets of 2 × 2 tables in a clinical trial, and within-subject differences in an ordinal response across ordinal factor levels within a repeated measures design. The underlying multiple hypergeometric probability structure, based on a randomization model framework for hypothesis testing, is summarized for testing alternative hypotheses of 1) general association; 2) mean responses differ; and 3) linear trend in mean responses. These generalized MH methods can all be implemented directly within SAS and StatXact, with appropriate stratification and choice of scores.


Keywords:

categorical data;
ordinal scores;
randomization model;
hypergeometric probability;
repeated measures

Stephen J. Kuritz

Papers

A General Overview of Mantel-Haenszel Methods: Applications and Recent Developments

Summary attributable risk estimation from unmatched case‐control data

Mantel–Haenszel Methods

Mantel–Haenszel Methods†