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PubMed2006

Bone strength: the whole is greater than the sum of its parts.

OBJECTIVE: To summarize the current knowledge regarding the various determinants of bone strength. METHODS: Relevant English-language articles acquired from Medline from 1966 up to January 2005 were reviewed. Searches included the keywords bone AND 1 of the following: strength, remodeling, microcrack, structur*, mineralization, collagen, organic, crystallinity, osteocyte, porosity, diameter, anisotropy, stress risers, or connectivity. Abstracts from applicable conference proceedings were also reviewed for pertinent information. RESULTS: Bone strength is determined from both its material and its structural properties. Material properties such as its degree of mineralization, crystallinity, collagen characteristics, and osteocyte viability have substantial impacts on bone strength. Structural properties such as the diameter and thickness of the cortices, the porosity of the cortical shell, the connectivity and anisotropy of the trabecular network, the thickness of trabeculae, and the presence of trabecular stress risers and microcracks impact bone strength in diverse manners. Remodeling activity either directly or indirectly impacts all of these processes. CONCLUSIONS: Bone strength is dependent on numerous, interrelated factors. Remodeling activity has a direct impact on almost all of the components of bone strength and requires further investigation as to its impact on these factors in isolation and in unison.

Bone Density↗
PubMed2000

Ginkgo biloba extract: mechanisms and clinical indications.

OBJECTIVE: Ginkgo biloba may have a role in treating impairments in memory, cognitive speed, activities of daily living (ADL), edema, inflammation, and free-radical toxicity associated with traumatic brain injury (TBI), Alzheimer's dementia, stroke, vasoocclusive disorders, and aging. The purpose of this review is to provide a synthesis of the mechanisms of action, clinical indications, and safety of Ginkgo biloba extract. DATA SOURCES: Empirical studies, reviews, chapters, and conference proceedings were identified in the following databases: Medline, the Research Council for Complementary Medicine based on the British Library database, and Psychlnfo. Ginkgo biloba, EGb 761, Tanakan, Tebonin, Rokan, and LI 1370 were the principal index terms. STUDY SELECTION AND DATA EXTRACTION: Controlled clinical studies with both positive and negative findings are included, in addition to animals studies illustrating mechanisms of activity. DATA SYNTHESIS: Ginkgo has shown activity centrally and peripherally, affecting electrochemical, physiologic, neurologic, and vascular systems in animals and humans with few adverse side effects or drug interactions. Ginkgo shows promise in patients with dementia, normal aging, and cerebrovascular-related disorders. Clinical indications include memory, information processing, and ADL. CONCLUSIONS: Ginkgo shows promise in treating some of the neurologic sequelae associated with Alzheimer's disease, TBI, stroke, normal aging, edema, tinnitus, and macular degeneration. Mechanisms of action may include antioxidant, neurotransmitter/receptor modulatory, and antiplatelet activating factor properties. While safe, caution is advised when recommending ginkgo to patients taking anticoagulants. Future studies should examine dose effects, component activity, mechanisms, and clinical applications.

Animals↗
PubMed2000

Andropause: a misnomer for a true clinical entity.

PURPOSE: A progressive decrease in androgen production is common in males after middle age. The resulting clinical picture has been erroneously named male menopause or andropause. A more appropriate designation is androgen decline in the aging male (ADAM). The syndrome is characterized by alterations in the physical and intellectual domains that correlate with and can be corrected by manipulation of the androgen milieu. We review the epidemiological aspects of aging and endocrinological manifestations of ADAM, and provide recommendations for treatment and monitoring of these patients. MATERIALS AND METHODS: We performed MEDLINE, Pubmed, Current Contents and Pharmaceutical Abstracts searches of relevant peer reviewed publications on andropause, male climacteric, adult hypogonadism and aging. In addition, conference proceedings were researched to provide a more complete review of the literature. Information was scrutinized and collated, and contributory data were reviewed and summarized. RESULTS: ADAM is a clinical entity characterized biochemically by a decrease not only in serum androgen, but also in other hormones, such as growth hormone, melatonin and dehydroepiandrosterone. Clinical manifestations include fatigue, depression, decreased libido, erectile dysfunction, and alterations in mood and cognition. CONCLUSIONS: The onset of ADAM is unpredictable and its manifestations are subtle and variable, which has led to a paucity of interest in its diagnosis and treatment. Urological practice commonly includes a large proportion of men older than 50 years. Therefore, it is important for urologists to recognize the manifestations of and be familiar with evaluations necessary to document ADAM as well as its treatment and monitoring.

Aged↗
PubMed2003

Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review.

OBJECTIVE: To examine the effectiveness of aspirin in preventing perinatal death and preeclampsia in women with predisposing historical risk factors, such as previous history of preeclampsia, chronic hypertension, diabetes, and renal disease. DATA SOURCES: Searches were conductes in Medline, Embase, Cochrane Library, National Research Register, SCISEARCH, AND ISI Conference Proceedings without any language restrictions, using the following medical subject headings and text words: "aspirin," "antiplatelet*," "salicyl*," "acetylsalicyl*," "platelet aggregation inhibitors," "pre-eclamp*," "preeclamp*," and "hypertens*. METHODS OF STUDY SELECTION: We included all randomized trials that evaluated the effectiveness of aspirin compared with placebo or no treatment in women with predisposing historical risk factors and reported clinically relevant perinatal or maternal outcomes. Study selection, quality appraisal, and data extractions were performed independently and in duplicate.We identified 14 relevant trials, including a total of 12,416 women. Meta-analysis showed a significant benefit of aspirin therapy in reducing perinatal death (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.64, 0.96) and preeclampsia (OR 0.86, 95% CI 0.76, 0.96). Aspirin was also associated with a reduction in rates of spontaneous preterm birth (OR 0.86, 95% CI 0.79, 0.94), and an increase of 215 g in mean birth weight (weighted mean difference 215, 95% CI 90, 341). There was no increase in the risk of placental abruption with aspirin (OR 0.98, 95% CI 0.79, 1.21). Funnel plot analysis indicated that publication and related biases were unlikely (Egger test, P =.84). CONCLUSION: Aspirin reduces the risk of perinatal death and preeclampsia in women with historical risk factors. Given the importance of these outcomes and the safety and low cost of aspirin, aspirin therapy should be considered in women with historical risk factors.

Aspirin↗
PubMed1993

Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8-10, 1991, World Health Organization meeting report.

In May 1991, researchers and clinicians from throughout the world met at a workshop sponsored by the Regional Office for Europe of the World Health Organization in collaboration with the Fondo de Investigación Sanitaria, Spain, and the U.S. Food and Drug Administration, National Institutes of Health, National Institutes of Mental Health, and Centers for Disease Control and Prevention to share information about two very similar diseases--toxic oil syndrome and eosinophilia-myalgia syndrome. In this paper the interpretation of conference proceedings is presented, current knowledge of the two disorders is summarized, and some possible areas for future research are mentioned. Toxic oil syndrome and eosinophilia-myalgia syndrome have many similarities. Both are related to consumer products that were presumed to be safe but have been found to have numerous trace contaminants, many of which remain to be identified, including the etiologic agents of both disorders. Both illnesses affect patients clinically by causing intense, incapacitating myalgias and a marked peripheral eosinophilia. Other rheumatologic manifestations are common in both, including arthralgias, sicca syndrome, scleroderma-like skin changes, carpal tunnel syndrome, and joint contractures. No clinical or laboratory feature has been found to be pathognomonic of either disease, and accurate diagnosis rests on the clinical judgment of the attending physician. Deaths have occurred in both diseases, and the cumulative mortality for each is approximately 2.5% for the first 2 years. Long-term complications include pulmonary hypertension, peripheral neuropathies, and joint contractures. Although treatment with corticosteroids has resulted in significant symptomatic relief in persons with either disorder, it does not alter the clinical course or long-term outcome. Research into the etiologic agents, preferred treatments, and ways to avoid similar problems in the future is needed.

Animals↗
PubMed2000

Risk of intracranial haemorrhage with bolus versus infusion thrombolytic therapy: a meta-analysis.

BACKGROUND: Although thrombolytic therapy given by bolus injection seems to be as effective as infusion over 60-90 min, no single trial has been adequately powered to detect clinically important safety differences between the two strategies. We did a meta-analysis to find out whether bolus administration of thrombolytics is associated with an increased frequency of intracranial haemorrhage. METHODS: We identified randomised trials comparing bolus with infusion thrombolytic therapy by a search of electronic databases, reference lists, and conference proceedings. Odds ratios for primary intracranial haemorrhage, non-haemorrhagic stroke, mortality, and reinfarction were calculated for each trial and were combined in a fixed-effects model. FINDINGS: Seven trials, involving a total of 103,972 patients, met our inclusion criteria. Bolus treatment was associated with an increased risk of intracranial haemorrhage compared with infusion (0.8 vs 0.6%; odds ratio 1.25 [95% CI 1.08-1.45]; p=0.003). The increased risk was most striking in trials comparing bolus with infusion administration of the same agent (1.75 [1.32-2.33], p=0.0001), but was also evident in trials comparing a newer-generation bolus agent with standard infusion therapy (1.25 [1.03-1.50]; p=0.02). The rates of non-haemorrhagic stroke (0.94 [0.81-1.09]), 30-day mortality (1.01 [0.97-1.06]), or reinfarction (1.04 [0.97-1.11]) did not differ between the two strategies. INTERPRETATION: The increased risk of bolus thrombolytic treatment seems to be primarily associated with the method of administration rather than properties of the agents. Although the increased risk of intracranial haemorrhage is small, physicians should balance this risk against the putative benefits of easier administration with no difference in mortality or reinfarction.

Fibrinolytic Agents↗
PubMed2001

Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials.

BACKGROUND: The optimum duration of prophylaxis against venous thromboembolism after total hip or knee replacement is uncertain. Our primary objective was to establish the efficacy of extended-duration prophylaxis on symptomatic venous thromboembolic events. METHODS: We identified randomised trials comparing extended-duration prophylaxis using heparin or warfarin with placebo or untreated control in patients undergoing elective total hip or knee replacement by searching electronic databases (MEDLINE, EMBASE), references from retrieved articles, and abstracts from conference proceedings, and by contact with pharmaceutical companies and investigators. Two reviewers independently extracted data on study design, symptomatic and symptomless venographic venous thromboembolism, death, and bleeding outcomes. Results from individual trials were combined with the Mantel-Haenszel method. FINDINGS: Nine studies met our inclusion criteria (3999 patients), eight with low molecular weight heparin, and one with unfractionated heparin. Extended-duration prophylaxis for 30-42 days significantly reduced the frequency of symptomatic venous thromboembolism (1.3% vs 3.3%, OR 0.38; 95% CI 0.24-0.61, numbers needed to treat [NNT]=50), with no statistical evidence of heterogeneity (x(2) test, p=0.69). There was a greater risk reduction in patients undergoing hip replacement (1.4% vs 4.3%, 0.33; 0.19-0.56, 34) compared with knee replacement (1.0% vs 1.4%, 0.74; 0.26-2.15, 250). A significant reduction in symptomless venographic deep vein thrombosis was also observed (9.6% vs 19.6%, 0.48; 0.36-0.63, 10). There was no increase in major bleeding but extended-duration prophylaxis was associated with excess minor bleeding (3.7% vs 2.5%, 1.56; 1.08-2.26, numbers needed to harm [NNH]=83). INTERPRETATION: Among patients undergoing total hip or knee replacement, extended-duration prophylaxis significantly reduces the frequency of symptomatic venous thromboembolism. The reduction in risk is equivalent to about 20 symptomatic events per 1000 patients treated.

Anticoagulants↗
PubMed1997

Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials.

BACKGROUND: Homeopathy seems scientifically implausible, but has widespread use. We aimed to assess whether the clinical effect reported in randomised controlled trials of homeopathic remedies is equivalent to that reported for placebo. METHODS: We sought studies from computerised bibliographies and contracts with researchers, institutions, manufacturers, individual collectors, homeopathic conference proceedings, and books. We included all languages. Double-blind and/or randomised placebo-controlled trials of clinical conditions were considered. Our review of 185 trials identified 119 that met the inclusion criteria. 89 had adequate data for meta-analysis, and two sets of trial were used to assess reproducibility. Two reviewers assessed study quality with two scales and extracted data for information on clinical condition, homeopathy type, dilution, "remedy", population, and outcomes. FINDINGS: The combined odds ratio for the 89 studies entered into the main meta-analysis was 2.45 (95% CI 2.05, 2.93) in favour of homeopathy. The odds ratio for the 26 good-quality studies was 1.66 (1.33, 2.08), and that corrected for publication bias was 1.78 (1.03, 3.10). Four studies on the effects of a single remedy on seasonal allergies had a pooled odds ratio for ocular symptoms at 4 weeks of 2.03 (1.51, 2.74). Five studies on postoperative ileus had a pooled mean effect-size-difference of -0.22 standard deviations (95% CI -0.36, -0.09) for flatus, and -0.18 SDs (-0.33, -0.03) for stool (both p < 0.05). INTERPRETATION: The results of our meta-analysis are not compatible with the hypothesis that the clinical effects of homeopathy are completely due to placebo. However, we found insufficient evidence from these studies that homeopathy is clearly efficacious for any single clinical condition. Further research on homeopathy is warranted provided it is rigorous and systematic.

Double-Blind Method↗
PubMed1998

Assessment of pain in the neonate.

This article critically reviews the measures developed for assessing pain in the human neonate. Information was gathered with a computerized literature search of published articles and abstracts, a manual review of relevant conference proceedings, recently published journals, unpublished reports and manuscripts, and personal files. This identified 16 measures that were critically examined for their psychometric properties (reliability and validity) and clinical use. Special emphasis was placed on the feasibility of using neonatal pain assessment measures for clinical practice to address the research-practice gap. Although considerable progress has been made in the field of neonatal pain assessment, few measures have adequately established psychometric properties and clinical utility. Furthermore, most measures have been developed for research and not for the clinical setting. Issues regarding sensitivity, specificity, and the ability to detect clinically important changes have not been addressed. A sufficient number of infant pain measures have now been developed to assess acute pain. There is a paucity of measures to assess chronic pain in infants, and measures for infants who are low birth weight, critically ill, or ventilated. Future research should be aimed at strengthening the properties of existing measures, and at the development of measures for those infants with chronic pain or special needs.

Behavior↗