Meta-analyses Of Clinical Studies Research Articles

Clinical studies and meta-analysis on the effects of collagen, vitamin, and nutrient supplementation for the rejuvenation of collagenic fibers: a systematic review

Introduction: Collagen prevails in connective tissues, constituting 80% of the dry weight of human skin. Aging induces a decline in enzymes involved in the post-translational processing of collagen, reducing the number of fibroblasts that synthesize collagen and the vessels that irrigate the skin. Oral ingestion of hydrolyzed collagen together with vitamins and nutrients (especially apple exosomes) increases the levels of collagenderived peptides in the bloodstream and improves skin properties. Objective: It was to carry out a systematic review to elucidate the main results of clinical studies and meta-analyses of clinical studies on the effects of supplementation of types of collagen, vitamins, and nutrients for the rejuvenation of collagen fibers. Methods: The search was carried out from October to December 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 122 articles were found, and 12 articles were evaluated in full, and 07 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 20 studies with a high risk of bias and 26 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=62.4%>50%. Oral nutritional supplements containing collagen peptides can reduce skin vulnerability in the elderly and thus prevent conditions such as skin lesions. The direct effects of collagen peptides on fibroblasts, M2-like macrophages, and mechanisms related to oral tolerance are the possible mechanisms for the beneficial effects of collagen supplementation. Special collagen peptides together with acerola extract, vitamin C, vitamin E, biotin, and zinc showed a significant improvement in the skin's collagen structure. The proven positive nutritional effect on collagen structure was fully consistent with the quality of healthy skin. Finally, apple-derived nanovesicles (exosomes) also reduce the degradation of the extracellular matrix, increasing collagen synthesis (COL3A1, COL1A2, COL8A1, and COL6A1) and negatively regulating the production of metalloproteinases.

Generalised decision curve analysis for explicit comparison of treatment effects.

Decision curve analysis (DCA) helps integrate prediction models with treatment assessments to guide personalised therapeutic choices among multiple treatment options. However, the current versions of DCA do not explicitly model treatment effects in the analysis but implicitly or holistically assess therapeutic benefits and harms. In addition, the existing DCA cannot allow the comparison of multiple treatments using a standard metric. To develop a generalised version of DCA (gDCA) by decomposing holistically assessed net benefits and harms into patient preferences versus empirical evidence (as obtained in the trials, meta-analyses of clinical studies, etc.) to allow individualised comparison of single or multiple treatments using a common metric. We reformulated DCA by (1) decomposing holistic, implicit utilities into specific utilities related to treatment effects and patient's relative values (RV) about disease outcomes versus treatment harms, (2) explicitly modelling each treatment effect at the level of probabilities and/or utilities (outcomes) in a decision tree, and (3) avoiding scaling effects employed in the original DCA to enable comparison of treatment effects against the common metrics. We used data from a published network meta-analysis of randomised trials to inform the use of statin treatment according to Framingham Risk Model. We illustrate the analysis by modelling the effects of three statins in the primary prevention of cardiovascular disease. We performed simultaneous comparisons against standard metrics (RV) for all treatments. We examined for which RV values, a predictive model for guiding personalised treatment, outperformed the strategies of treating everyone or treating no one. We found that the magnitude of benefits (efficacy) seems more important than the simple ratio of efficacy/harms. We describe gDCA for evaluating single or multiple treatments to help tailor therapy toward individual risk characteristics. gDCA further helps integrate the principles of evidence-based medicine with decision analysis.

The effect of psychosocial interventions on infertility: Inconsistency of research data.

This systematic review aimed to investigate the inconsistency of research data concerning the contribution of systematic psychosocial interventions to infertility treatments. More specifically, the objective of this review was to investigate the cause of the contradictions in the results of contemporary research with respect to the role of systematic psychosocial interventions in the success of fertility treatments. The suspected cause of these contradictions is the heterogeneity of the relevant clinical studies with respect to their methodology. Thus, the specific aim of the current review was to evaluate the degree of heterogeneity of certain parameters in the design of the relevant clinical studies during the last decade, including sample heterogeneity, assisted reproductive technology methods, types of psychosocial interventions and methods of recording and analyzing psychometric data. This investigation may be considered imperative considering that despite the great number of relevant clinical studies and their meta-analyses, there are still no conclusive results concerning the potential of improving fertility through psychosocial support. Search for relevant studies was performed employing the PubMed and Google Scholar databases based on specific criteria. According to these criteria the selected publications have been meta-analyses of clinical studies on humans, evaluating the effect of psychosocial interventions on the success of assisted reproductive treatments during the last decade. The studies may have included all the different infertility etiologies, as well as all types of assisted reproductive treatments. The extensive search based on the specific inclusion/exclusion criteria resulted in reporting results from 6 studies in total. The clinical studies included have reported on various types of interventions for psychosocial support such as individual, couples' or group therapies performed either in facilities offering mental health services or in the form of home-based self-treatment. Moreover, these studies investigated various techniques of stress management ranging from counseling to specialized methods such as biofeedback and diaphragmatic breathing or alternative techniques such as yoga and meditation. Our results suggest that clinical studies designed specifically to evaluate the effect of systematic interventions on the efficacy of fertility treatments are limited. Moreover, their degree of heterogeneity is highly significant with respect to included participants, treatment protocols, psychosocial support techniques as well as methods for the documentation and statistical analysis of psychometric data. Consequently, the conduction of well-design clinical studies based on strict criteria aiming to investigate specific infertility causes, similar fertility treatment protocols or particular types of psychosocial interventions is necessary in order to reach definitive conclusions.

Role of Probiotics in Stimulating the Immune System in Viral Respiratory Tract Infections: A Narrative Review.

Viral respiratory tract infection (RTI) is the most frequent cause of infectious illnesses including the common cold. Pharmacological solutions for treating or preventing viral RTIs are so far limited and thus several self-care products are available in the market. Some dietary supplements such as probiotics have been shown to modulate immune system function and their role in reducing the risk and the course of RTIs has been investigated extensively within the past decade. However, the mechanism of action and the efficacy of probiotics against viral RTIs remains unclear. We searched PubMed, Google Scholar, and Web of Knowledge for pre-clinical and clinical studies investigating the effect of probiotics on respiratory virus infections, immune response, and the course of upper and lower respiratory tract illness. The literature summarized in this narrative review points out that specific probiotic strains seem effective in pre-clinical models, through stimulating the immune system and inhibiting viral replication. Clinical studies indicate variable efficacy on upper respiratory illnesses and lack proof of diagnosed viral infections. However, meta-analyses of clinical studies indicate that probiotics could be beneficial in upper respiratory illnesses without specific etiology. Further studies aiming at discovering the mechanisms of action of probiotics and clinical efficacy are warranted.

Reduction of blood glucose by plant extracts and their use in the treatment of diabetes mellitus; discrepancies in effectiveness between animal and human studies.

The global problem of diabetes, together with the limited access of large numbers of patients to conventional antidiabetic medicines, continues to drive the search for new agents. Ancient Asian systems such as traditional Chinese medicine, Japanese Kampo medicine, and Indian Ayurvedic medicine, as well as African traditional medicine and many others have identified numerous plants reported anecdotally to treat diabetes; there are probably more than 800 such plants for which there is scientific evidence for their activity, mostly from studies using various models of diabetes in experimental animals. Rather than a comprehensive coverage of the literature, this article aims to identify discrepancies between findings in animal and human studies, and to highlight some of the problems in developing plant extract-based medicines that lower blood glucose in patients with diabetes, as well as to suggest potential ways forward. In addition to searching the 2018 PubMed literature using the terms 'extract AND blood glucose, a search of the whole literature was conducted using the terms 'plant extracts' AND 'blood glucose' AND 'diabetes' AND 'double blind' with 'clinical trials' as a filter. A third search using PubMed and Medline was undertaken for systematic reviews and meta-analyses investigating the effects of plant extracts on blood glucose/glycosylated haemoglobin in patients with relevant metabolic pathologies. Despite numerous animal studies demonstrating the effects of plant extracts on blood glucose, few randomised, double-blind, placebo-controlled trials have been conducted to confirm efficacy in treating humans with diabetes; there have been only a small number of systematic reviews with meta-analyses of clinical studies. Qualitative and quantitative discrepancies between animal and human clinical studies in some cases were marked; the factors contributing to this included variations in the products among different studies, the doses used, differences between animal models and the human disease, and the impact of concomitant therapy in patients, as well as differences in the duration of treatment, and the fact that treatment in animals may begin before or very soon after the induction of diabetes. The potential afforded by natural products has not yet been realised in the context of treating diabetes mellitus. A systematic, coordinated, international effort is required to achieve the goal of providing anti-diabetic treatments derived from medicinal plants.

Pharmacogenomic Information In The Treatment Of Major Depression: Results From A Randomized Clinical Trial

Mental disorders are one of the leading causes of disability globally. Inherited genetic variation in pharmacokinetic (PK) and pharmacodynamic (PD) genes may contribute to the observed interindividual differences in clinical efficacy and tolerability of psychopharmaceuticals. Therefore, strategies for improving effectiveness of pharmacological treatments translating pharmacogenomic information from bench to clinic have been recently attempted. However, effectiveness of available psychiatric pharmacogenomic tools in ameliorating clinical symptoms has not been analyzed in populations of suitable size by means of adequately powered multicentric randomized clinical trials.The Neuropharmagen personalized medicine platform integrates pharmacogenomic data from the analysis of PK and PD genes to provide actionable recommendations for psychoactive drugs, including genotype-specific dose adjustments and the risk of specific adverse effects based on FDA-approved drug labelling, Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, and meta-analyses of clinical studies. Moreover, within the Neuropharmagen platform, pharmacogenomic recommendations can be complemented combined with alerts on drug-drug, drug-clinical condition and drug-environmental factor interactions. Notably, the later can be updated by the doctor whenever there are changes in the condition of the patient or the pharmacological treatment.Clinical efficacy of the Neuropharmagen test has been evaluated in two multicentric clinical studies totaling 462 patients analyzed for the primary outcome at study endpoint. A retrospective study evaluating patients with different psychiatric diagnoses and at least 1 treatment failure found that patients whose treatment followed the pharmacogenetic (PGx) test recommendations had odds of improvement about 4 times higher than patients whose treatment did not (adjusted OR = 3.86, 95%CI 1.36–10.95; p = 0.011). Recently, we have completed a prospective randomized clinical trial conducted in 316 patients with major depressive disorder with a wide range of depression severities and number of treatment failures. In this talk, I will describe the main results of both studies, with a major focus in those obtained in the multicentric randomized clinical trial. Overall, the combined results of studies conducted with Neuropharmagen show that PGx-guided treatment constitutes a significant tool to improve clinical response and medication tolerability, especially in subjects with moderate to severe depression and in those with previous failed drug trials.

A two-step screening approach for the identification of blood donors with highly and broadly neutralizing capacities against human cytomegalovirus.

Hyperimmunoglobulins are frequently applied for prophylaxis and treatment of human cytomegalovirus (HCMV) infections but were only marginally effective in meta-analyses of clinical studies. This might be partially due to selection of donors rather for total anti-HCMV titers than for neutralizing capacities. To improve efficacy against HCMV infection, we aimed at developing a high-throughput screening method for identification of blood donors with highly and broadly neutralizing capacities. Using a Gaussia luciferase-expressing reporter virus, 1000 HCMV immunoglobulin (Ig)G-positive plasma samples with known anti-HCMV immunoglobulin titers were analyzed regarding their neutralization titers against fibroblast and endothelial cell infection. Based on these results, a high-throughput screening was designed. Highly neutralizing plasma samples were further tested 1) by an enzyme-linked immunosorbent assay-based neutralization assay regarding efficiency against different HCMV strains and 2) for their efficiency compared to commercially available hyperimmunoglobulins. Total anti-HCMV immunoglobulin titers did not correlate with neutralization. Mean neutralization capacities were 15-fold higher in endothelial cells compared to fibroblasts. All plasma samples neutralizing fibroblast infection were at least equally effective against infection of endothelial cells, providing the possibility to simplify our screening method by testing only fibroblasts as target cells with a plasma dilution of 1 in 400. Of the nine tested top HCMV neutralizers, four were broadly effective against different HCMV strains. All nine were significantly superior to hyperimmunoglobulins. Donors with highly and broadly neutralizing capacities can be identified by a two-step high-throughput screening approach. This may provide a basis for improved antibody-based treatment or prophylaxis of HCMV infections.

Abstract 428: Lipoprotein(a) Targeting With RNAi Delivery Platforms in Transgenic Mice and Cynomolgus Monkeys

Background: Meta-analyses of clinical studies have demonstrated that high levels of lipoprotein(a), known as Lp(a), correlate with residual risk of cardiovascular disease (CVD) while Mendelian genetic studies indicate that Lp(a) is an independent cause of CVD. Lp(a) is a complex lipoprotein particle similar in structure to LDL (consisting of cholesterol, triglycerides, phospholipids and apoB-100), but contains the genetically variable liver-expressed protein apo(a). Lp(a) may contribute to atherosclerosis by targeting oxidized phospholipids to vascular injury sites, promoting both inflammation and accumulation of lipids. Methods: RNA interference (RNAi) based approaches for reducing liver apo(a) expression were developed using both a targeted intravenous platform called Dynamic Polyconjugates (DPC) TM and a subcutaneous (SQ) format. The DPC platform comprises an RNAi trigger conjugated to cholesterol, and a hepatocyte-targeted, membrane active peptide to promote endosomal release of the RNAi trigger. The SQ platform is an RNAi trigger targeted to liver by N-acetyl galactosamine in a proprietary format. RNAi activity was assessed in two different humanized transgenic mice and cynomolgus monkeys. Results: In Lp(a) transgenic mice expressing human apo(a) and apoB-100 genes, treatment with a single DPC dose reduced serum Lp(a) by >98% at nadir and >90% for >5 weeks. A single DPC injection in cynomolgus monkeys resulted in >95% reduction in endogenous Lp(a) particles at 5 weeks post injection, without significant changes in toxicity biomarkers. Treatment with a SQ RNAi trigger reduced serum apo(a) in transgenic mice by >90% at nadir, while that in monkeys reached 64% reduction of Lp(a). Additional modifications to the RNAi trigger improved both depth and duration of knockdown in transgenic mice. Conclusion: Long-duration reductions in circulating apo(a) and Lp(a) have been shown with hepatocyte-directed delivery of apo(a)-specific RNAi triggers in mice and monkeys. This represents an intriguing mechanism to evaluate in humans for reducing residual risk of CVD in LDL-controlled individuals with elevated Lp(a).

An overview of systematic reviews on the effectiveness of periodontal treatment to improve glycaemic control.

Several systematic reviews with meta-analyses on the effectiveness of periodontal treatment to improve glycaemic control have been published. So far no overview of these systematic reviews has been performed. The main objective of this report was to assess critically these systematic reviews to provide the reader with a high-level synthesis of research evidence. MEDLINE (via PubMed) and EMBASE databases were searched independently and in duplicate to identify systematic reviews with meta-analyses of clinical studies that assessed the relationship between diabetes mellitus and periodontitis. The last database search was performed on 10 March 2015. The reference lists of included systematic reviews were also scrutinized for further publications. The methodological quality of the included systematic reviews was assessed independently with two validated checklists (AMSTAR and OQAQ) by two authors. Disagreements in the assessment were resolved by consensus. A total of 226 potential publications were initially retrieved. Eleven systematic reviews with meta-analyses were finally included. Glycosylated haemoglobin A1c (HbA1c) was the most commonly used clinical endpoint. Meta-analytic estimates from systematic reviews generated an average reduction of 0.46% (median 0.40%) of HbA1c in patients with diabetes mellitus who received periodontal treatment. These meta-analyses had, nevertheless, methodological limitations such as inclusion of trials with different types of risk of bias that hinder more robust conclusions. A recent meta-analysis that included recently published large randomized controlled trials did not show significant change in the level of HbA1c at the 6 mo follow-up. The AMSTAR checklist generated results that were more conservative than OQAQ. Findings from this overview do not support the information that periodontal treatment may improve glycaemic control. Methodological issues described in this overview may guide further research on this topic.

Effects of Pioglitazone on Bone in Postmenopausal Women With Impaired Fasting Glucose or Impaired Glucose Tolerance: A Randomized, Double-Blind, Placebo-Controlled Study

Meta-analyses of clinical studies have suggested an increased incidence of peripheral fractures in postmenopausal women with type 2 diabetes mellitus taking pioglitazone. The mechanism behind this apparent increase is unknown. The objective of the study was to examine the effects of pioglitazone on bone mineral density (BMD) and turnover. Twenty-five sites (in the United States) enrolled participants in this randomized, double-blind, placebo-controlled study. Postmenopausal women (n = 156) with impaired fasting glucose or impaired glucose tolerance participated in the study. The intervention consisted of pioglitazone 30 mg/d (n = 78) or placebo (n = 78), increased to 45 mg/d after 1 month, for 12 months of treatment total, followed by 6 months of washout/follow-up. Percentage changes from baseline to month 12 and from month 12 to month18 in BMD in total proximal femur (primary end point), total body, femoral neck, lumbar spine, and radius were measured. Least squares mean changes from baseline to month 12 in total proximal femur BMD were -0.69% for pioglitazone and -0.14% for placebo (P = .170). No statistically significant between-group differences were observed for any BMD or bone remodeling marker end point. We observed improved glycemic control and insulin sensitivity with pioglitazone treatment. In addition, pioglitazone appeared to increase body fat, which may affect bone density measurements, especially in the lumbar spine. One pioglitazone-treated and three placebo-treated women experienced confirmed fractures. Over 18 months, one pioglitazone-treated (1.3%) and eight placebo-treated women (10.3%) developed overt type 2 diabetes mellitus. The pattern and incidence of adverse events with pioglitazone were consistent with clinical experience with thiazolidinediones. Maximal-dose pioglitazone had no effects on BMD or bone turnover, while improving glycemic control as expected, in postmenopausal women with impaired fasting glucose or impaired glucose tolerance.

Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies

We carried out a systematic review of clinical studies investigating glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test. Random effects models for the primary meta-analysis and random effects meta-regression, subgroup and regression analyses were applied. Random effects meta-analysis of GLP-1 responses in 22 trials during 29 different stimulation tests showed that patients with type 2 diabetes (n = 275) and controls without type 2 diabetes (n = 279) exhibited similar responses of total GLP-1 (p = NS) as evaluated from peak plasma concentrations (weighted mean difference [95% CI] 1.09 pmol/l [-2.50, 4.67]), total AUC (tAUC) (159 pmol/l × min [-270, 589]), time-corrected tAUC (tAUC min⁻¹) (0.99 pmol/l [-1.28, 3.27]), incremental AUC (iAUC) (-122 pmol/l × min [-410, 165]) and time-corrected iAUC (iAUC min⁻¹) (-0.49 pmol/l [-2.16, 1.17]). Fixed effects meta-analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes. Subgroup analysis showed increased responses after a liquid mixed meal test (peak, tAUC and tAUC min⁻¹) and after a 50 g OGTT (AUC and tAUC min⁻¹), and reduced responses after a solid mixed meal test (tAUC min⁻¹) among patients with type 2 diabetes. Meta-regression analyses showed that HbA1c and fasting plasma glucose predicted the outcomes iAUC and iAUC min⁻¹, respectively. The present analysis suggests that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test, and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion.

Organisation, data evaluation, interpretation and effect of arthroplasty register data on the outcome in terms of revision rate in total hip arthroplasty

Originally developed in Scandinavia, national arthroplasty registers have spread worldwide during the last decade. The value of registers for quality improvement in arthroplasty has frequently been documented. However, for the development of a successful register a few key points should be taken into account. Uncontrolled loss of patients from the registry area should be avoided. Registers should form an integral part of a country's medical system. To realise the potential for improvement, it is crucial that physicians deal with the results in detail. Thus it is absolutely essential to involve the specialty societies in the interpretation and dissemination of results. With respect to revision rates, register data are usually more valid than meta-analyses of clinical studies. For every physician the most valuable data are those coming from a register in his own country; the development of national arthroplasty registers should therefore be continued.

Hämatopoetische Wachstumsfaktoren

The production of hematopoietic cells is under the tight control of distinct growth factors. As therapeutic agents, granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoiesis-stimulating agents (TSA) are in routine clinical use. Granulocyte colony-stimulating factor is used to prevent febrile neutropenia or to increase dose-density in chemotherapy regimens. Despite a reduced duration of neutropenia, randomized controlled trials have documented only a modest clinical benefit. A clinical advantage of dose-dense chemotherapy has been shown only in specific chemotherapy regimens. Clinical practice guidelines recommend the use of G-CSF for patients with a high risk of adverse outcome of febrile neutropenia. Erythropoiesis-stimulating agents (ESAs) are used as an alternative to blood transfusion in patients with chemotherapy-induced anemia. However, recent meta-analyses of clinical studies suggest that their use was associated with an increased risk of all-cause mortality and serious adverse events. Thrombopoiesis-stimulating agents have been introduced recently into the market for patients with immune thrombocytopenic purpura. Prior to the use of TSA in other conditions such as chemotherapy-induced thrombocytopenia the lessons learned with G-CSF and ESAs should be taken into account.

Continuing medical education article—patient safety: The need for venous thromboembolism (VTE) prophylaxis in plastic surgery

The reader is presumed to have a broad understanding of plastic surgical procedures and concepts. After studying this article, the participant should be able to: Physicians may earn 1 AMA PRA Category 1 credit credit by successfully completing the examination based on material covered in this article. The examination begins on page 176. ASAPS members can also complete this CME examination online by logging onto the ASAPS Members-Only Web site (http://www.surgery.org/members) and clicking on "Clinical Education" in the menu bar. Little has been published about venous thromboembolism (VTE) complications in plastic surgery. The authors investigated the recent literature, particularly literature reviews and meta-analyses of clinical studies, in order to outline strategies for prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) applicable to plastic surgery patients. Major risk factors for VTE include trauma, a prior history of VTE, older age, use of oral contraceptives or hormone replacement therapy, and prolonged travel. Although the frequency of VTE among plastic surgery patients is estimated to be from less than 1% to 2% of cases, in fact many of our patients are at moderate to high risk of VTE. Moreover, the actual frequency of VTE among plastic surgery patients is probably higher than we know, because up to two thirds of cases are asymptomatic. Mechanical methods of VTE prophylaxis include graduated compression stockings (GCSs), intermittent pneumatic compression (IPC) devices, and venous foot pumps (VFPs). They are recommended primarily for patients with a high risk of bleeding or as an adjunct to chemoprophylaxis. Intermittent pneumatic compression devices were found to be more effective than passive compression using GCSs. For plastic surgery patients, IPC devices or VFPs are recommended for any procedure that lasts more than 1 hour, and for all patients receiving general anesthesia. Use should begin 30 to 60 minutes before surgery. Low-molecular-weight heparin (LMWH) is the most widely used form of DVT/PE prophylaxis. Other forms of chemoprophylaxis are coming onto the market or under development. In particular, fondaparinux, an indirect FXa inhibitor, was approved in 2004 for VTE prophylaxis in orthopedic surgery. Studies have indicated that it is significantly more effective than LMWH after joint replacement, hip fracture surgery, and in cancer patients. Other drugs in development include idraparinux, another indirect FXa inhibitor, direct FXa inhibitors, and several direct thrombin inhibitors. Plastic surgeons have generally been reluctant to use antithrombotic agents because of the increased risk of bruising or hematoma and the possible need for blood transfusion. However, numerous studies have found little or no increase in the frequency of clinically important bleeding associated with their use. Some plastic surgeons now routinely use chemoprophylaxis in patients undergoing abdominoplasty, combined procedures, or procedures lasting more than 4 hours. The authors also recommend postoperative chemoprophylaxis in circumferential body contouring, thighplasty, surgery requiring open space dissection, transverse rectus abdominus muscle (TRAM) procedures, and surgical procedures likely to contribute to venous stasis or compression. It is impractical and expensive to screen every patient for asymptomatic DVT. A patient history focusing specifically on VTE risk factors should be performed within a few weeks of surgery. Patient education should include information about the symptoms of DVT and PE (including the fact that most patients with VTE are asymptomatic) and a full explanation of the risks and benefits of anticoagulant prophylaxis.

Localization-independent Regulation of Homocysteine Secretion by Phosphatidylethanolamine N-Methyltransferase

Genetic ablation of phosphatidylethanolamine N-methyltransferase (PEMT) in mice causes a 50% reduction in plasma homocysteine (Hcy) levels. Because hyperhomocysteinemia is an independent risk factor for cardiovascular disease, resolution of the molecular basis for this reduction is of significant clinical interest. The PEMT pathway is a metabolically channeled process localized to the endoplasmic reticulum (ER). To assess the importance of PEMT localization for Hcy homeostasis, we identified and ablated the minimal ER targeting motif. Mutagenesis of a conserved, C-terminal lysine residue (197) relocalized the enzyme to the Golgi, demonstrating that Lys-197 is essential for targeting PEMT to the ER. To evaluate the functional significance of PEMT localization, hepatoma cell lines were generated that stably expressed either ER- or Golgi-localized PEMT only. Intriguingly, stable expression of PEMT in either the ER or the Golgi caused increased Hcy secretion. Moreover, PEMT-mediated Hcy secretion correlated with the methyltransferase activity of the enzyme, independently of subcellular localization. Thus, our data suggest that Hcy homeostasis is regulated concomitantly with PEMT activity but independently of PEMT localization.

Epidemiology and treatment of left ventricular hypertrophy in the elderly.

Left ventricular hypertrophy (LVH) is an important independent risk factor for cardiovascular disease and is associated with an increased risk of ventricular dysrhythmia, coronary artery disease, myocardial infarction, stroke, heart failure and peripheral artery disease. The prevalence of LVH increases strongly with advancing age and, consequently, the prevention or reduction of LVH should be an important consideration in the older age-group. This review summarises current knowledge on LVH and discusses management issues with particular reference to the elderly. Evidence suggests that antihypertensive treatment can reverse or prevent LVH. There have been few studies of LVH in the elderly, but since age does not appear to be a factor in the regression of LVH, results of studies among younger hypertensive patients can be extrapolated to the elderly population. Meta-analyses of clinical studies have not established conclusively that angiotensin-converting enzyme inhibitors and calcium antagonists are necessarily more effective than diuretics and beta-adrenoceptor antagonists in reducing LVH.