Efficacy of combined oral contraceptives for depressive symptoms and overall symptomatology in premenstrual syndrome:pairwise and network meta-analysis of randomized trials

OBJECTIVE: Combined oral contraceptives are often considered a treatment option for women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) also seeking contraception, but evidence for this treatment is scarce. We aimed to determine 1) the level of evidence for the efficacy of combined oral contraceptives in managing premenstrual depressive symptoms and overall premenstrual symptomatology, and 2) the comparative efficacy of combined oral contraceptives (PROSPERO registration number CRD42020205510). DATA SOURCES: We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, Emcare, and EMBASE from inception to June 3rd, 2021. STUDY ELIGIBILITY: All randomized clinical trials that evaluated efficacy of combined oral contraceptives in women with PMS or PMDD were considered eligible for inclusion in the present meta-analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: A random effect Bayesian pairwise and network meta-analysis was conducted with change in premenstrual depressive symptoms and overall premenstrual symptomatology between baseline and 3 cycles as outcome. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Of 3664 records, nine eligible trials were included that studied 1205 women with PMS or PMDD (mean age per study range: 24.6-36.5 years). The pairwise meta-analysis revealed that combined oral contraceptives were more efficacious than placebo in treating overall premenstrual symptomatology (standardized mean difference SMD [95%CrI], 0.41 [0.17, 0.67]), but not premenstrual depressive symptoms specifically (SMD [95%CrI], 0.22 [-0.06, 0.47]). However, none of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology. CONCLUSIONS: Combined oral contraceptives may improve overall premenstrual symptomatology in women with PMS or PMDD, but not premenstrual depressive symptoms. There is no evidence for one combined oral contraceptive being more efficacious than any other

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Where is SUSY?

The direct searches for Superymmetry at colliders can be complemented by direct searches for dark matter (DM) in underground experiments, if one assumes the Lightest Supersymmetric Particle (LSP) provides the dark matter of the universe. It will be shown that within the Constrained minimal Supersymmetric Model (CMSSM) the direct searches for DM are complementary to direct LHC searches for SUSY and Higgs particles using analytical formulae. A combined excluded region from LHC, WMAP and XENON100 will be provided, showing that within the CMSSM gluinos below 1 TeV and LSP masses below 160 GeV are excluded (m_{1/2} > 400 GeV) independent of the squark masses.Comment: 16 pages, 10 figure

Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands

Aims: to investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands. Materials & methods: A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing. Results: Pharmacogenetic dosing increased costs by €33 and QALYs by 0.001. The incremental cost-effectiveness ratios (ICERs) were €28,349 and €24,427 per QALY gained for phenprocoumon and acenocoumarol respectively. At a willingness to pay threshold of €20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be cost-effective compared to the clinical dosing algorithm. Conclusions: Pharmacogenetic dosing improves health only slightly when compared with clinical dosing. However, availability of low-cost genotyping would make it a cost-effective option

Future of Pharmacogenetics in Cardiovascular Diseases

Introduction: Pharmacogenetics is the study of variations in DNA sequence as related to drug response (European Medicines Agency [EMA], 2007). Several gene-drug interactions have been discovered in the field of cardiovascular diseases (CVDs). These gene-drug interactions can help to identify nonresponse to drugs, estimate dose requirements or identify an increased risk of developing adverse drug reactions. An individualized approach based on pharmacogenetic testing will provide physicians and pharmacists with tools for decision making about pharmacotherapy. While pharmacogenetic testing is already part of everyday practice in oncology, it is not widely implemented in the field of CVDs. However, in the near future, pharmacogenetics will probably also play a valuable role in this field as well

Cost-effectiveness of new oral anticoagulants for stroke prevention in patients with atrial fibrillation in two different European healthcare settings

Objectives: To investigate the cost-effectiveness of apixaban, rivaroxaban and dabigatran, compared to coumarin derivatives for stroke prevention in patients with atrial fibrillation in a country with specialized anticoagulation clinics (The Netherlands) and in a country without these clinics (the United Kingdom). Methods: A decision-analytic Markov model was used to analyse the cost-effectiveness of apixaban, rivaroxaban and dabigatran compared to coumarin derivatives in The Netherlands and the United Kingdom over a lifetime horizon. Results: In the Netherlands, the use of rivaroxaban, apixaban or dabigatran increased health by 0.166, 0.365 and 0.374 quality-adjusted life-years (QALYs) compared to coumarin derivatives, but also increased costs by €5,681, €4,754 and €5,465, respectively. The incremental cost-effectiveness ratios (ICERs) were €34,248, €13,024 and €14,626 per QALY gained. In the United Kingdom, health was increased by 0.302, 0.455 and 0.461 QALYs and the incremental costs were similar for all three new oral anticoagulants (€5,118 to €5,217). The ICERs varied from €11,172 to €16,949 per QALY gained. In The Netherlands, apixaban had the highest chance (37%) to be cost-effective at a threshold of €20,000 and in the United Kingdom this chance was 41% for dabigatran. The quality of care reflected in time in therapeutic range had an important influence on the ICER. Conclusions: Apixaban, rivaroxaban and dabigatran are cost-effective alternatives to coumarin derivatives in the United Kingdom, while in The Netherlands, only apixaban and dabigatran could be considered cost-effective. The cost-effectiveness of the new oral anticoagulants is largely dependent on the setting and quality of local anticoagulant care facilities

Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients

Obstetric anal sphincter injury: a systematic review of information available on the internet.

OBJECTIVE: There is no systematic evaluation of online health information pertaining to obstetric anal sphincter injury. Therefore, we evaluated the accuracy, credibility, reliability, and readability of online information concerning obstetric anal sphincter injury. MATERIALS AND METHODS: Multiple search engines were searched. The first 30 webpages were identified for each keyword and considered eligible if they provided information regarding obstetric anal sphincter injury. Eligible webpages were assessed by two independent researchers for accuracy (prioritised criteria based upon the RCOG Third and Fourth Degree Tear guideline); credibility; reliability; and readability. RESULTS: Fifty-eight webpages were included. Seventeen webpages (30%) had obtained Health On the Net certification, or Information Standard approval and performed better than those without such approvals (p = 0.039). The best overall performing website was http://www.pat.nhs.uk (score of 146.7). A single webpage (1%) fulfilled the entire criteria for accuracy with a score of 18: www.tamesidehospital.nhs.uk . Twenty-nine webpages (50%) were assessed as credible (scores ≥7). A single webpage achieved a maximum credibility score of 10: www.meht.nhs.uk . Over a third (21 out of 58) were rated as poor or very poor. The highest scoring webpage was http://www.royalsurrey.nhs.uk (score 62). No webpage met the recommended Flesch Reading Ease Score above 70. The intra-class coefficient between researchers was 0.98 (95% CI 0.96-0.99) and 0.94 (95% CI 0.89-0.96) for accuracy and reliability assessments. CONCLUSION: Online information concerning obstetric anal sphincter injury often uses language that is inappropriate for a lay audience and lacks sufficient accuracy, credibility, and reliability