Summary
Purpose: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy

Methods:  Participants were adults with medically refractory partial seizures, including secondarily generalized seizures Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation

Results:  One hundred ten participants were randomized Baseline monthly median seizure frequency was 195 In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0002) Unadjusted median declines at the end of the blinded phase were 145% in the control group and 404% in the stimulated group Complex partial and “most severe” seizures were significantly reduced by stimulation By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months Five deaths occurred and none were from implantation or stimulation No participant had symptomatic hemorrhage or brain infection Two participants had acute, transient stimulation-associated seizures Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events

Discussion:  Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures Benefit persisted for 2 years of study Complication rates were modest Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures

/pdf/electrical-stimulation-of-the-anterior-nucleus-of-thalamus-4v93q45fg4.pdf

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy

Statistical Methods in Medical Research.

Objective

To estimate the lifetime risk of symptomatic knee osteoarthritis (OA), overall and stratified by sex, race, education, history of knee injury, and body mass index (BMI).



Methods

The lifetime risk of symptomatic OA in at least 1 knee was estimated from logistic regression models with generalized estimating equations among 3,068 participants of the Johnston County Osteoarthritis Project, a longitudinal study of black and white women and men age ≥45 years living in rural North Carolina. Radiographic, sociodemographic, and symptomatic knee data measured at baseline (1990–1997) and first followup (1999–2003) were analyzed.



Results

The lifetime risk of symptomatic knee OA was 44.7% (95% confidence interval [95% CI] 40.0–49.3%). Cohort members with history of a knee injury had a lifetime risk of 56.8% (95% CI 48.4–65.2%). Lifetime risk rose with increasing BMI, with a risk of 2 in 3 among those who were obese.



Conclusion

Nearly half of the adults in Johnston County will develop symptomatic knee OA by age 85 years, with lifetime risk highest among obese persons. These current high risks in Johnston County may suggest similar risks in the general US population, especially given the increase in 2 major risk factors for knee OA, aging, and obesity. This underscores the immediate need for greater use of clinical and public health interventions, especially those that address weight loss and self-management, to reduce the impact of having knee OA.

/pdf/lifetime-risk-of-symptomatic-knee-osteoarthritis-39y8ew8ouo.pdf

Lifetime risk of symptomatic knee osteoarthritis

The International Agency for Research on Cancer (IARC) was established in 1965 by the World Health Assembly, as an independently funded organisation within the framework of the World Health Organization. The headquarters of the Agency are in Lyon, France. The Agency conducts a programme of research concentrating particularly on the epidemiology of cancer and the study of potential carcinogens in the human environment. Its field studies are supplemented by biological and chemical research carried out in the Agency's laboratories in Lyon and, through collaborative research agreements, in national research institutions in many countries. The Agency also conducts a programme for the education and training of personnel for cancer research. The publications of the Agency contribute to the dissemination of authoritative information on different aspects of cancer research. Information about IARC publications, and how to order them, is available via the Internet at: http:// The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. The authors alone are responsible for the views expressed in this publication.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.11334

IARC Handbooks of Cancer Prevention

BackgroundThe optimal range of sodium intake for cardiovascular health is controversial. MethodsWe obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. ResultsThe mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow-up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (≥7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high esti...

/pdf/urinary-sodium-and-potassium-excretion-mortality-and-505ucx83jh.pdf

Urinary Sodium and Potassium Excretion, Mortality, and Cardiovascular Events

The method of generalized estimating equations (GEE) is often used to analyze longitudinal and other correlated response data, particularly if responses are binary. However, few descriptions of the method are accessible to epidemiologists. In this paper, the authors use small worked examples and one real data set, involving both binary and quantitative response data, to help end-users appreciate the essence of the method. The examples are simple enough to see the behind-the-scenes calculations and the essential role of weighted observations, and they allow nonstatisticians to imagine the calculations involved when the GEE method is applied to more complex multivariate data.

https://faculty.washington.edu/heagerty/Courses/VA-longitudinal/private/Hanley-2003AJE.pdf

Statistical Analysis of Correlated Data Using Generalized Estimating Equations: An Orientation

The method of generalized estimating equations has become almost standard for analysing longitudinal and other correlated response data. However, we have found that if binary responses have less than binomial variation over clusters, and are modelled using exchangeable correlations, prevailing software implementations may give unreliable results. Bounding the negative correlation away from its theoretical minimum may not always be a satisfactory solution. In such instances, using the independence working correlation structure and robust SEs is a more trustworthy alternative.

/pdf/gee-analysis-of-negatively-correlated-binary-responses-a-1m8rrf3llx.pdf

GEE analysis of negatively correlated binary responses: a caution.

A Correction has been published for this article in Statisitcs in Medicine 2000; 19(21): 3017.

Familiar measures of association for 2 × 2 tables are the odds ratio, the risk ratio and the risk difference. Analagous measures of outcome–exposure association are desirable when there are several degrees of severity of both exposure and disease outcome. One such measure (α), which we label the general odds ratio (ORG), was proposed by Agresti. Convenient methods are given for calculation of both standard error and 95 per cent confidence intervals for ORG. Other approaches to generalizing the odds ratio entail fitting statistical models which might not fit the data, and cannot handle some zero frequencies. We propose a generalization of the risk ratio (RRG) following the statistical approaches of Agresti, Goodman and Kruskal. A method of calculating the standard error and 95 per cent confidence interval for RRG is provided. A known statistic, Somers' d, fulfils the characteristics necessary for a generalized risk difference (RDG). These measures have straightforward interpretations, are easily computed, are at least as precise as other methods and do not require fitting statistical models to the data. We also examine the pooling of such measures as in, for example, meta-analysis. Copyright © 2000 John Wiley & Sons, Ltd.

The generalization of the odds ratio, risk ratio and risk difference to r x k tables.

https://jamanetwork.com/journals/jama/articlepdf/1031362/jlt0613.pdf

MMR immunization and autism.

Kendall's τ is equal to the correlation coefficient for the BVE distribution

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