Weight-modification trials in older adults: what should the outcome measure be?

Background

Overweight older adults are often counseled to lose weight, even though there is little evidence of excess mortality in that age group. Overweight and underweight may be more associated with health status than with mortality, but few clinical trials of any kind have been based on maximizing years of healthy life (YHL), as opposed to years of life (YOL).

Objective

This paper examines the relationship of body mass index (BMI) to both YHL and YOL. Results were used to determine whether clinical trials of weight-modification based on improving YHL would be more powerful than studies based on survival.

Design

We used data from a cohort of 4,878 non-smoking men and women aged 65–100 at baseline (mean age 73) and followed 7 years. We estimated mean YHL and YOL in four categories of BMI: underweight, normal, overweight, and obese.

Results

Subjects averaged 6.3 YOL and 4.6 YHL of a possible 7 years. Both measures were higher for women and whites. For men, none of the BMI groups was significantly different from the normal group on either YOL or YHL. For women, the obese had significantly lower YHL (but not YOL) than the normals, and the underweight had significantly lower YOL and YHL. The overweight group was not significantly different from the normal group on either measure.

Conclusions

Clinical trials of weight loss interventions for obese older women would require fewer participants if YHL rather than YOL was the outcome measure. Interventions for obese men or for the merely overweight are not likely to achieve differences in either YOL or YHL. Evaluations of interventions for the underweight (which would presumably address the causes of their low weight) may be conducted efficiently using either outcome measure.

     

Hereditary hemochromatosis genetic testing of at-risk children: what is the appropriate age?

The objective of this study was to consider the objective evidence and ethical arguments for the appropriate age to test children at risk of developing hereditary hemochromatosis. A literature search for information on iron overload in children, onset of disease expression for hemochromatosis, and recommendations for age of cascade screening was undertaken. We examined the objective evidence and arguments for testing in early childhood and those for delaying testing until later teenage years. Cascade testing of offspring of people with hemochromatosis is widely advocated because it is an easily preventable disease. The ideal age to test those offspring is a matter of debate. Some authorities advocate testing at a very young age whereas others recommend delaying testing until late teenage years. To date there has been no published overview of the objective evidence and arguments central to this debate. In children who are C282Y homozygous, iron overload is rare in the first two decades of life and associated morbidity has only been documented in 1 patient. In the cascade setting, genetic testing for hemochromatosis need not be offered until late teenage years.     

Cancer of the lung: what should be the present approach?

The best opportunities at present for improving the results in the treatment of patients with cancer of the lung are by way of (a) utilizing the information obtained on routine x-ray examination of the chest, (b) decreasing the delay between the time of the first symptoms and the time the patient consults a physician, and (c) decreasing the delay between the time the patient first consults a physician and the time the cancer is surgically removed. The medical profession must increase its index of suspicion of cancer of the lung and persist in efforts to make a diagnosis when lung cancer is suspected. Exploratory thoracotomy should be used in suspicious cases when the diagnosis cannot be established by other methods.     

Mastering health: liberating beauty: Will the cosmetics of tomorrow be genetic?

Systems that have yet to stand the test of time carry imperfections that need to be skillfully addressed with the least amount of authoritarianism as possible. The communication and transmission of knowledge that we hold dear are essential pillars to social progress. As such, it is necessary to analyze with the greatest scientific objectivity the applications arising from the deep revolution rooted in the total sequencing of the human genome which affects all aspects of our societies. This extraordinary advance in human knowledge and the resulting technological achievements should not lend themselves to the fears or fantasies often fueled by those who criticize all scientific progress calling into question the most established dogmas. Certain supposedly scholarly analyses of the health situation with which we are currently confronted worldwide are a perfect illustration of this unfortunate trend. It is undeniable that the progress of molecular genetics has opened up a wide range of applications in many fields, affecting the well-being of humans, their mental and physical health. The apparent universal and individual interest for the most advanced genetic profile analyzing technologies is a testimony to this strong common desire to better understand one’s genetic heritage and to control their usage. Despite this movement, little attention is given to the recent advances in genetics applied to essential aspects of the social life of individuals through their inter-personal interactions. It is particularly distressing that the contributions of molecular biology and genetics to the daily well-being of individuals have not yet allowed open-access non-medical genetic testing to gain the recognition it deserves and are still viewed as recreational applications. Through an analysis of the cross influences that genetic biotechnologies have had since the beginning of the century in the fields of nutrition and cosmetics, we have tried to project ourselves into the near future which should witness major behavioral and social upheavals.     

What should the Z-score of native protein structures be?

The Z-score of a protein is defined as the energy separation between the native fold and the average of an ensemble of misfolds in the units of the standard deviation of the ensemble. The Z-score is often used as a way of testing the knowledge-based potentials for their ability to recognize the native fold from other alternatives. However, it is not known what range of values the Z-scores should have if one had a correct potential. Here, we offer an estimate of Z-scores extracted from calorimetric measurements of proteins. The energies obtained from these experimental data are compared with those from computer simulations of a lattice model protein. It is suggested that the Z-scores calculated from different knowledge-based potentials are generally too small in comparison with the experimental values.     

Sensitivity of the Pap test in detecting high grade lesions: what should be the acceptable cytologic threshold for colposcopic referral?

OBJECTIVE: To devise an optimal cytology threshold for colposcopy referral in resource-limited settings. STUDY DESIGN: Four hundred seventy-two symptomatic women 20-60 years old were screened by both cytology and colposcopy. Onsite biopsy was taken if lesions grade 1 or above were detected on colposcopy. Women found to have cervical intraepithelial neoplasia (CIN) 2 and above lesions on histopathology were stratified according to their cytologic diagnosis (atypical squamous cells of undetermined significance [ASCUS]+ threshold, low grade squamous intraepithelial lesion [LSIL]+ threshold, and high grade squamous intraepithelial lesion [HSIL]+ threshold). The comparative sensitivity, specificity and predictive values in each group were calculated, taking biopsy as the gold standard. RESULTS: The sensitivity of LSIL + cytology to detect CIN 2+ lesions was 91.5% (referral load, 30.7%). While the sensitivity of ASCUS+ cytology threshold was almost the same (92.3%), the referral load was much higher (42.2%). With HSIL+ cytology threshold, though the referral load was reduced substantially (21.9%), the sensitivity also decreased, to 81.5%. CONCLUSION: The results indicate that in order to achieve high sensitivity, the LSIL cytology threshold appears to be optimum for colposcopic referrals.     

Hallmarks of cancer: of all cancer cells,all the time?

In two landmark articles, Hanahan and Weinberg synthesized into one conceptual framework 'the hallmarks of cancer', a massive amount of information describing the characteristics of a cancer cell. Although this is neither the intention nor the belief of the authors, hallmarks are often interpreted as applying to a canonic cancer cell, or equally to all cells within a cancer. In this article, we clarify the separate concepts of causes, oncogenic events, signal transduction programs, and hallmarks to show that there is no unimodal relation between these concepts but a complex network of interrelations that vary in different cells, between cells, and at different times in any given cell. We consider cancer as an evolving, dynamic, and heterogeneous system, explaining, at least in part, the difficulty of treating cancer and supporting the use of simultaneous, multitarget therapies.     

Commercialisation of entomopathogenic nematodes: should import regulations be revised?

Entomopathogenic nematodes (EPNs) in the families Steinernematidae and Heterorhabditidae are obligate insect pathogens. Their favourable characteristics as biocontrol agents have resulted in some species of EPNs being released globally and widely used for the control of diverse insect pests. In this review, we consider the occurrence of currently described EPN species, including those that have been released globally for commercial purposes. We also discuss the contribution of regulation policies to the global distribution of these species and issues that influence import regulations. Possible non-target effects, the use of commercial versus native EPNs and the possible interaction between these species are considered. Finally, we provide a view as to whether existing policies adequately deal with the risks associated with the global movement of EPNs and we suggest future directions that should be considered for the use of EPNs as biological control agents.     

PCR detection of cryptosporidium: the way forward?

In this article, Una Morgan and Andrew Thompson briefly review the latest information on polymerase chain reaction (PCR)detection of Cryptosporidium parvum in both clinical and environmental samples. Current detection methods for Cryptosporidium are cumbersome, time-consuming and lack sensitivity. A variety of PCR tests have been described recently in the literature and this article discusses the advantages and disadvantages of each new technique and their potential for future diagnosis of Cryptosporidium.     

Primary aldosteronism: who should be screened?

Primary aldosteronism (PA) has a prevalence in the general hypertensive population from 5 to 10%, and is widely recognized as the most frequent form of secondary hypertension. The 2 main PA subtypes are aldosterone producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) that account for 95% of all PA cases. The diagnosis of PA is a 3-step process that comprises screening, confirmatory testing, and subtype differentiation. The different categories of patients at an increased risk of PA who should thus undergo a screening test were described in the first Endocrine Society (ES) Practice Guidelines for diagnosis and treatment of PA published in 2008. These categories include patients with Joint National Committee Stage 2, Stage 3, or drug-resistant hypertension; hypertension, and spontaneous or diuretic-induced hypokalemia; hypertension with adrenal incidentaloma; hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age and all hypertensive first degree relatives of patients with PA. Recently, a growing number of studies have linked PA with the metabolic syndrome, diabetes, and obstructive sleep apnea that may be partly responsible for the higher rate of cardio and cerobrovascular accidents in PA patients. The aim of this review is to discuss, which patients should be screened for PA, focusing not only on the well-established categories of the ES Guidelines, but also on additional other group of patients with a potentially high prevalence of PA that has emerged from recent research.