Treatment of symptoms of the menopause: an endocrine society clinical practice guideline

Objective: The objective of this document is to generate a practice guideline for the management and treatment of symptoms of the menopause. Participants: The Treatment of Symptoms of the Menopause Task Force included six experts, a methodologist, and a medical writer, all appointed by The Endocrine Society. Evidence: The Task Force developed this evidenced-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned three systematic reviews of published data and considered several other existing meta-analyses and trials. Consensus Process: Multiple e-mail communications, conference calls, and one face-to-face meeting determined consensus. Committees of The Endocrine Society, representatives from endorsing societies, and members of The Endocrine Society reviewed and commented on the drafts of the guidelines. The Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society (co-sponsors of the guideline) reviewed and commented on the draft. Conclusions: Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms and other symptoms of the climacteric. Benefits may exceed risks for the majority of symptomatic postmenopausal women who are under age 60 or under 10 years since the onset of menopause. Health care professionals should individualize therapy based on clinical factors and patient preference. They should screen women before initiating MHT for cardiovascular and breast cancer risk and recommend the most appropriate therapy depending on risk/benefit considerations. Current evidence does not justify the use of MHT to prevent coronary heart disease, breast cancer, or dementia. Other options are available for those with vasomotor symptoms who prefer not to use MHT or who have contraindications because these patients should not use MHT. Low-dose vaginal estrogen and ospemifene provide effective therapy for the genitourinary syndrome of menopause, and vaginal moisturizers and lubricants are available for those not choosing hormonal therapy. All postmenopausal women should embrace appropriate lifestyle measures

Association between industry affiliation and position on cardiovascular risk with rosiglitazone: cross sectional systematic review

Objective To explore a possible link between authors’ financial conflicts of interest and their position on the association of rosiglitazone with increased risk of myocardial infarction in patients with diabetes

A systematic review and meta-analysis of randomized trials of carotid endarterectomy vs stenting

ObjectiveThe purpose of this systematic review and meta-analysis was to synthesize the available evidence derived from randomized controlled trials (RCTs) regarding the relative efficacy and safety of endarterectomy vs stenting in patients with carotid artery disease.MethodsWe searched MEDLINE, EMBASE, Current Contents, and Cochrane CENTRAL through July 2010 to update previous systematic reviews. Two reviewers determined trial eligibility and extracted descriptive, methodologic, and outcome data (death, nonfatal stroke, and nonfatal myocardial infarction). Random-effects meta-analysis was used to pool relative risks and the I2 statistic was used to assess heterogeneity.ResultsThirteen RCTs proved eligible enrolling 7484 patients, of which 80% had symptomatic disease. Methodological quality was moderate to high, with better quality among RCTs published after 2008. Compared with carotid endarterectomy, stenting was associated with increased risk of any stroke (relative risk [RR], 1.45; 95% confidence interval [CI], 1.06-1.99; I2 = 40%), decreased risk of periprocedural myocardial infarction (MI; RR, 0.43; 95% CI, 0.26- 0.71; I2 = 0%), and nonsignificant increase in mortality (RR, 1.40; 95% CI, 0.85-2.33; I2 = 5%). When analysis was restricted to the two most recent trials with the better methodology and more contemporary technique, we found stenting to be associated with a significant increase in the risk of any stroke (RR, 1.82; 95% CI, 1.35-2.45) and mortality (RR, 2.53; 95% CI, 1.27-5.08) and a nonsignificant reduction of the risk of MI (RR, 0.39; 95% CI, 0.12-1.23). For every 1000 patients opting for stenting rather than endarterectomy, 19 more patients would have strokes and 10 fewer would have MIs. Outcome data in asymptomatic patients were sparse and imprecise; hence, these conclusions apply primarily to symptomatic patients.ConclusionCompared with endarterectomy, carotid artery stenting (CAS) significantly increases the risk of any stroke and decreases the risk of MI

Overexpression, purification and characterization of the Aspergillus niger endoglucanase, EglA, in Pichia pastoris>/i>

Cellulases are industrially important hydrolytic enzymes applicable in the bioconversion of cellulosic biomass to simple sugars. In this work, an endoglucanase from Aspergillus niger ATCC 10574, EglA, was expressed in the methylotrophic yeast Pichia pastoris and the properties of the recombinant protein were characterized. The full length cDNA of eglA has been cloned into a pPICZαC expression vector and expressed extracellularly as a ~30 kDa recombinant protein in P. pastoris X-33. Pure EglA displayed optimum activity at 50°C and was stable between 30 and 55°C. The pH stability of this enzyme was shown to be in the range of pH 2.0 to 7.0 and optimum at pH 4.0. EglA showed the highest affinity toward β-glucan followed by carboxymethyl cellulose (CMC) with a specific activity of 63.83 and 9.47 U/mg, respectively. Very low or no detectable hydrolysis of cellobiose, laminarin, filter paper and avicel were observed. Metal ions such as Mn2+, Co2+, Zn2+, Mg2+, Ba2+, Fe2+, Ca2+ and K+ showed significant augmentation of endoglucanase activity, with manganese ions causing the highest increase in activity to about 2.7 fold when compared with the control assay, whereas Pd2+, Cu2+, SDS and EDTA showed inhibition of EglA activity.Key words: Cellulase, endoglucanase, recombinant, Aspergillus niger, Pichia pastoris

The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

Abstract Objective: To develop clinical practice guidelines for the management of patients with primary aldosteronism. Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee of the Endocrine Society, six additional experts, a methodologist, and a medical writer. The guideline was cosponsored by American Heart Association, American Association of Endocrine Surgeons, European Society of Endocrinology, European Society of Hypertension, International Association of Endocrine Surgeons, International Society of Endocrinology, International Society of Hypertension, Japan Endocrine Society, and The Japanese Society of Hypertension. The Task Force received no corporate funding or remuneration. Evidence: We searched for systematic reviews and primary studies to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations and "suggest" for weak recommendations. Consensus Process: We achieved consensus by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. With the help of a medical writer, the Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and Council successfully reviewed the drafts prepared by the Task Force. We placed the version approved by the Clinical Guidelines Subcommittee and Clinical Affairs Core Committee on the Endocrine Society's website for comments by members. At each stage of review, the Task Force received written comments and incorporated necessary changes. Conclusions: For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist

Improving the interpretation of quality of life evidence in meta-analyses: the application of minimal important difference units

Systematic reviews of randomized trials that include measurements of health-related quality of life potentially provide critical information for patient and clinicians facing challenging health care decisions. When, as is most often the case, individual randomized trials use different measurement instruments for the same construct (such as physical or emotional function), authors typically report differences between intervention and control in standard deviation units (so-called "standardized mean difference" or "effect size"). This approach has statistical limitations (it is influenced by the heterogeneity of the population) and is non-intuitive for decision makers. We suggest an alternative approach: reporting results in minimal important difference units (the smallest difference patients experience as important). This approach provides a potential solution to both the statistical and interpretational problems of existing methods

Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis

Objective To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. Data sources We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. Study selection Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks' treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. Data extraction and synthesis Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. Outcomes Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δb) in the number of SBM/week and Δb CSBM/week. Results Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δb in number of SBM/week. Conclusions Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δb in the number of SBM/week in CIC

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

OBJECTIVE: To formulate clinical practice guidelines for the pharmacological management of obesity. PARTICIPANTS: An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence. CONCLUSIONS: Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health