Volume 3, Number 3: March 2000

Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia

Development of Guidelines

Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life.

Central nervous system and plasma lipid profiles associated with carteolol and timolol in postmenopausal black women.

Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia

Reference: J Am Coll Cardio 2000;35(2):265-270.

 OBJECTIVE

This work was undertaken to determine whether dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia.

BACKGROUND

Marine omega-3 fatty acids improve vascular function, but the underlying mechanism(s) are unclear. We studied the effects of marine omega-3 fatty acids on large artery endothelial function in subjects with hypercholesterolemia.

METHODS

Hypercholesterolemic subjects with no other known cause for endothelial dysfunction were recruited to a prospective, placebo-controlled, randomized, double-blind, parallel-group study. Treatment with omega-3 fatty acids at a dose of 4 g/day (n = 15/group) was compared with placebo, at the beginning (day 0) and end (day 120) of a four-month treatment period. Endothelial function was assessed pre- and posttreatment by noninvasive ultrasonic vessel wall tracking of brachial artery flow-mediated dilation (FMD).

RESULTS

Treatment with marine omega-3 fatty acids resulted in a significant improvement in FMD (0.05 ± 0.12 to 0.12 ± 0.07 mm, p < 0.05) and a significant reduction in triglycerides (2.07 ± 1.13 to 1.73 ± 0.95 mmol/liter, p < 0.05), whereas treatment with placebo resulted in no change in FMD (0.03 ± 0.10 to 0.04 ± 0.10 mm) or triglycerides (2.29 ± 2.09 to 2.05 ± 1.36 mmol/liter) (both p < 0.05 treated compared with control). Responses to sublingual glyceryl trinitrate were unchanged.

CONCLUSIONS

Marine omega-3 fatty acids improve large artery endothelium-dependent dilation in subjects with hypercholesterolemia without affecting endothelium-independent dilation.

Development of Guidelines

Reference: Lancet 2000;355(9198):82-3.

The emphasis of debate among guideline developers in recent years has shifted largely from the ''what'' of evidence-based guidelines to the ''how''. Statements of the key principles underpinning the development of evidence-based guidelines  have been superseded by more detailed descriptions   of the methods that have been devised to develop guidelines that are multidisciplinary, that are based on a systematic review of published work, and that explicitly link the recommendations to the supporting evidence.

In today's Lancet, Roberto Grilli and colleagues show that most of the guidelines produced by specialty societies still do not meet these basic principles of guideline development. The question is: does it matter? It does matter very much. The development of guidelines that do meet these criteria may be time-consuming, but has the potential to lead to widespread ownership across the professions and patients, and to implementation by health services working in partnership. Development of guidelines that do not meet such defined criteria is of decidedly limited value, or worse. Advocacy guidelines developed by a single-specialty group in isolation may be counterproductive, because those disciplines and professions that were not involved in the development of the guideline but may be required to implement the recommendations mount their attacks and lodge their disclaimers. Some of these guidelines may be of the Good Old Boys Sat At Table (GOBSAT) variety, based on received wisdom rather than current scientific evidence, and may be biased by undeclared conflicts of interests.

There is now a considerable research base to indicate which methods of guideline production are most likely to alter professional decision making, and to provide clear evidence for the importance of the three criteria chosen by Grilli and colleagues as the basis of their study:

• Multidisciplinary development: Studies have shown that the balance of disciplines within a guideline-development group has considerable influence on the guideline recommendations. Widespread multidisciplinary participation is essential not only to ensure that the guideline is valid, but also that it is valued by all the members of the multidisciplinary team, in order to be incorporated successfully into practice.
• Guidelines based on a consensus of expert opinion or on unsystematic literature surveys have been widely criticised as not reflecting current medical knowledge and being liable to bias. To minimise potential sources of bias in the guideline recommendations, the literature should be identified according to an explicit search strategy, selected according to defined inclusion criteria, and assessed against consistent methodological standards.
• Graded recommendations: Guideline recommendations are graded to differentiate between those based on strong evidence and those based on weak evidence, this judgment being made on the basis of an (objective) assessment of the study design and quality and a (perhaps more subjective) judgment of the consistency, clinical relevance, and external validity of the evidence. The essential point is that the basis of the guideline-development group's recommendations should be transparent to enable guideline users to judge the appropriateness of each recommendation for an individual patient's circumstance.
  
  The Scottish Intercollegiate Guidelines Network (SIGN) and other guideline developers in the UK and Europe know what a task it is to develop multidisciplinary guidelines based on a systematic literature review that is comprehensive and rigorous, yet to complete the work within a tight time-scale and limited budget, and to derive and grade guideline recommendations in a valid and reproducible way. Not surprisingly many of the guidelines reviewed by Grilli and colleagues did badly on these key criteria.
  
  However, as the investigators point out, the problem might not be in the guideline-development process but in the reporting of it. Although rejection of an otherwise rigorously developed guideline on such grounds might seem to be a pity, it is reasonable to assume that an evidence-based guideline should in turn provide evidence as to its own validity, and that guidelines should be treated as ''guilty until proven innocent'' in this respect. This view does not mean that guideline recommendations should be buried beneath exhaustive methodological descriptions of the development process: the key elements can be summarised succinctly, and the internet is ideal for making background information widely available while the guidelines themselves are kept clear and concise.
  
  As Grilli and colleagues emphasise, medical journals also have a key role in encouraging the introduction of minimum standards for the reporting of the development of clinical-practice guidelines. Such standards would bring substantial benefits, not only in ensuring that guideline users have the information needed to assess the applicability, importance, and likely validity of any individual guideline, but also in enabling guideline developers to share elements of the development process, thus avoiding duplication of work and proliferation of guidelines.

Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life.

Reference: Diabetes Res Clin Pract 2000;47(2):123-8.

A prospective survey study was performed in patients with painful diabetic polyneuropathy (PDN) to assess the nature and scope of their pain. Pain associated with diabetic neuropathy is commonly encountered in clinical practice. Yet, little is known regarding the pain experience and impact on quality of life in persons with painful diabetic neuropathy. These 105 patients noted an average of 6/10 pain, most often described as 'burning', 'electric', 'sharp', and 'dull/ache', which, for most, is worse at night time and when tired or stressed. On average, patients reported that the pain caused substantial interference in sleep and enjoyment of life and moderate interference in recreational activities, normal work, mobility, general activity, social activities, and mood. Unexpectedly, a potential genetic predisposition to the development of painful neuropathy was suggested by the fact that a majority (56%) reported a family member with PDN. Thus, this study found that pain associated with diabetic neuropathy is a significant medical issue that has a substantial impact on the quality of life of many people with this condition.

Central nervous system and plasma lipid profiles associated with carteolol and timolol in postmenopausal black women.

Reference: J Glaucoma 1999;8(6):388-95.

PURPOSE: Among ocular hypotensive agents, intrinsic sympathomimetic activity (ISA) is unique to carteolol hydrochloride. This study was conducted to evaluate the central nervous system (CNS) and plasma lipid profiles associated with timolol maleate and carteolol hydrochloride in postmenopausal black women with primary open-angle glaucoma (POAG) or ocular hypertension.

 

METHODS: One hundred subjects met the inclusion and exclusion criteria for this randomized, double-masked, multicenter, parallel-group study. After completion of informed consent and complete ophthalmic examination, eligible patients entered a washout period, during which no topical ophthalmic medications were used. Blood samples were obtained for hematology and blood chemistry evaluations. Vital signs, ocular symptoms, Symptom Checklist-90-R (SCL-90-R) evaluation, intraocular pressure (IOP) measurements, and slit-lamp examinations were performed before randomization to treatment with either topical carteolol hydrochloride 1.0% or topical timolol maleate 0.5%. Patients received active medications twice daily and were monitored at 4 weeks and 12 weeks. At the conclusion of treatment, vital signs, ocular symptoms, SCL-90-R evaluation, IOP, slit-lamp examinations, and blood samples were obtained.

 

RESULTS: Compared with baseline, high-density lipoprotein (HDL) cholesterol was significantly decreased (worsened) in the timolol group but did not change significantly in the carteolol group. The between-group difference was statistically significant. Total cholesterol to HDL ratio significantly increased (worsened) in the timolol group compared with baseline but did not change in the carteolol group. The difference between groups was statistically significant. No significant differences were observed between groups in SCL-90-R results for either somatization or depression.

 

CONCLUSIONS: These results suggest that topical carteolol hydrochloride may have a more favorable blood lipid profile than topical timolol maleate in postmenopausal black women with POAG or ocular hypertension. Carteolol and timolol appear to have similar CNS side effect profiles.