Pseudotumor cerebri syndrome with different types of hormonal contraceptives in women of child-bearing age.

BACKGROUND AND PURPOSE: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. METHODS: We conducted a retrospective cohort study, with a case-control analysis of 4 871 504 women aged 15-45 years in the period 2008-2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. RESULTS: A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98-9.96] and 2.20 (95% CI 1.33-3.64), respectively. CONCLUSIONS: This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings.

Aromatase inhibitors and the risk of colorectal cancer in postmenopausal women with breast cancer.

Background: A large trial of postmenopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in postmenopausal women with breast cancer. Patients and methods: Using the UK Clinical Practice Research Datalink, we identified women, at least 55 years of age, with breast cancer newly treated with either AIs or tamoxifen between 1 January 1996 and 30 September 2015, with follow-up until 30 September 2016. High-dimensional propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident colorectal cancer associated with AIs when compared with tamoxifen overall, by cumulative duration of use, and time since initiation. All exposures were lagged by 1 year for latency considerations. Results: A total of 9701 and 8893 patients initiated AIs and tamoxifen as first-line hormonal therapy (median follow-up of 2.4 and 2.9 years, respectively). Compared with tamoxifen, AIs were not associated with an increased risk of colorectal cancer (incidence rates of 150 per 100 000 person-years in both groups; adjusted HR: 0.90, 95% CI: 0.53-1.52). Similarly, there was no evidence of an association with cumulative duration of use (P-heterogeneity = 0.54), and time since initiation (P-heterogeneity = 0.66). Conclusions: In this first population-based study, the use of AIs was not associated with an increased risk of colorectal cancer. These findings should provide reassurance to the concerned stakeholders.

Drospirenone-containing oral contraceptive pills and the risk of venous thromboembolism: a systematic review of observational studies.

BACKGROUND: The effects of fourth-generation drospirenone-containing combined oral contraceptives (COCs) on the risk of venous thromboembolism (VTE) are controversial. OBJECTIVES: To assess the methodological strengths and limitations of the evidence on the VTE risk of these COCs. SEARCH STRATEGY: We searched CINAHL, the Cochrane Library, EMBASE, HealthStar, Medline, and the Science Citation Index. SELECTION CRITERIA: Studies were included if they were cohort and case-control studies, reported a venous thrombotic outcome, had a comparator group, reported an effect measure of the association of interest, and were published in English or French. DATA COLLECTION AND ANALYSIS: We assessed study quality using the ROBINS-I tool and assessed the presence of four common sources of bias: prevalent user bias, inappropriate choice of comparator, VTE misclassification, and confounding. MAIN RESULTS: Our systematic review included 17 studies. The relative risks of VTE associated with drospirenone- versus second-generation levonorgestrel-containing COCs ranged from 1.0 to 3.3. Based on ROBINS-I, three studies had a moderate risk, ten had a serious risk, and four had a critical risk. Nine studies included prevalent users, four included inappropriate comparators, four had VTE misclassification, and five did not account for two or more important confounding factors. The three highest quality studies had relative risks ranging from 1.0 to 1.57. AUTHOR'S CONCLUSIONS: As a result of the methodological limitations of the individual studies, the VTE risk of drospirenone-containing COCs remains unknown. The highest quality studies suggest there are no or slightly increased harmful effects, but their confidence limits do not rule out an almost doubling of the risk. TWEETABLE ABSTRACT: Systematic review of drospirenone: best studies show no or slightly increased VTE risk (versus levonorgestrel).

Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: Aromatase inhibitors (AIs) have been associated with cardiovascular disease in adjuvant randomized controlled trials (RCTs) comparing these drugs to tamoxifen. However, it is unclear whether this risk is real or due to cardioprotective effects of tamoxifen. To address this question, we conducted a systematic review and meta-analysis of all RCTs of AIs and tamoxifen in adjuvant and extended adjuvant setting. Patients and methods: We searched PubMed, Embase (OVID), Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to June 2016 for all RCTs comparing cardiovascular and cerebrovascular safety of AIs to tamoxifen, AIs to placebo or no-treatment, or tamoxifen to placebo or no-treatment in the adjuvant or extended adjuvant setting. Relative risks (RRs) were pooled using DerSimonian and Laird random-effects models with analyses stratified by RCT design. Results: A total of 19 RCTs were included in the meta-analysis (n = 62 345). In the adjuvant setting, AIs were associated with a 19% (RR: 1.19, 95% confidence interval [CI]: 1.07-1.34) increased risk of cardiovascular events compared with tamoxifen. AIs were not associated with an increased risk compared with placebo in the extended-adjuvant setting (RR: 1.01, 95% CI: 0.85-1.20). In the adjuvant setting, tamoxifen was associated with a 33% (RR: 0.67, 95% CI: 0.45-0.98) decreased risk compared with placebo or no-treatment. The results from extended adjuvant RCTs comparing tamoxifen to placebo were inconclusive but suggestive of a small protective effect (RR: 0.91, 95% CI: 0.77-1.07). Conclusions: The increased risk of cardiovascular events with AIs relative to tamoxifen is likely the result of cardioprotective effects of the latter. This new evidence should be considered when assessing the benefits and risks of AIs in the treatment of breast cancer.

Accurate and consistent automatic seismocardiogram annotation without concurrent ECG.

Seismocardiography (SCG) is the measurement of vibrations in the sternum caused by the beating of the heart. Precise cardiac mechanical timings that are easily obtained from SCG are critically dependent on accurate identification of fiducial points. So far, SCG annotation has relied on concurrent ECG measurements. An algorithm capable of annotating SCG without the use any other concurrent measurement was designed. We subjected 18 participants to graded lower body negative pressure. We collected ECG and SCG, obtained R peaks from the former, and annotated the latter by hand, using these identified peaks. We also annotated the SCG automatically. We compared the isovolumic moment timings obtained by hand to those obtained using our algorithm. Mean ± confidence interval of the percentage of accurately annotated cardiac cycles were [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] for levels of negative pressure 0, -20, -30, -40, and -50 mmHg. LF/HF ratios, the relative power of low-frequency variations to high-frequency variations in heart beat intervals, obtained from isovolumic moments were also compared to those obtained from R peaks. The mean differences ± confidence interval were [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] for increasing levels of negative pressure. The accuracy and consistency of the algorithm enables the use of SCG as a stand-alone heart monitoring tool in healthy individuals at rest, and could serve as a basis for an eventual application in pathological cases.

Moving toward automatic and standalone delineation of seismocardiogram signal.

The purpose of this research is to propose an algorithm that could accomplish automatic delineation of the seismocardiogram (SCG) signal without using a reference electrocardiogram R-wave. As a result, the SCG signal could be used, as a stand-alone solution for many cardiovascular medical applications such as hemorrhage detection, cardiac computed tomographic gating, cardiac resynchronization therapy, hemodynamics estimations and diastolic timed vibration. Multiple envelopes were derived from the seismocardiogram signal by using filtering and triple integration. The first envelope is referred as the heart rate envelope, which has the characteristics of having a period of exactly one cardiac cycle and its purpose is to replace the ECG R-wave as a reference point. Our dataset is based on the lower body negative pressure (LBNP) test that was conducted on 18 individuals, containing 21610 cardiac cycles. For 94% of the LBNP dataset, the aforementioned envelope estimated heart rate within 3 beats per minute. Three different peaks of the SCG signal are of our interest: isovolumic contraction (IM), aortic valve opening (AO) and aortic valve closure (AC). For each of these desired peaks of the SCG signal, a different envelope was designed in a manner that its peak is very close to IM, AO and AC, respectively. For the same lower body negative pressure data set, a mean difference of (9, 9, 6) and standard deviation of (8, 9, 9) millisecond between the peak of envelopes and IM, AO and AC is accomplished. This could be used as a good initial estimation of the annotation points.

A new seismocardiography segmentation algorithm for diastolic timed vibrations.

An algorithm based on the combination of electrocardiography (ECG) and seismocardiogranphy (SCG) is used to detect the start and the end of diastole in diastolic timed vibrations (DTV). The proposed algorithm uses the ECG-R wave as the reference point and detects the aortic valve closure (AC) and mitral valve closure (MC) points of the SCG signal. This algorithm enables DTV to operate very efficiently in comparison with previous ECG based algorithm. Prediction rate of 95 and 88 percent was achieved for detection of SCG-MC and SCG-AC respectively.

Precordial acceleration signals improve the performance of diastolic timed vibrations.

BACKGROUND AND OBJECTIVE: This paper introduces a seismocardiography based methodology of predicting the start and the end of diastole to be used in diastolic timed vibrations (DTV), which provides non-invasive emergency treatment of acute coronary thrombosis by applying direct mechanical vibrations to the patient chest during diastole of heart cycles. It is proposed that seismocardiogram (SCG), in combination with electrocardiogram (ECG), provides a new means of diastole prediction. METHODS: An accelerometer was placed on the sternum of 120 healthy participants and 22 ischemic heart patients to record precordial accelerations created by the heart. The accelerometer signal was used to extract SCG and phonocardiogram (PCG). Two independent trained experts annotated the extracted signals based on the timings of the start and end of diastole. RESULTS: In the ischemic heart disease population by using 15 consecutive SCG cycles, the start and end of diastole was predicted in the upcoming cycles with 95 percentile error margin of 10.7 ms and 5.8 ms, respectively. These error margins were 7.4 ms and 3.5 ms, respectively, for normal participants. CONCLUSION: The results provide that prediction of the aortic valve closure point in the SCG signal helps start the vibrator in time to cover most of the isovolumic relaxation period. Also, through prediction of the mitral valve closure point in the SCG signal, safety of the technique can be assessed through prediction of the amount of unwanted vibrations applied during the isovolumic contraction period.

Preferred patterns of diastolic timed vibrations for pre-hospitalization treatment of acute coronary ischemia.

This paper presents and evaluates preferred patterns of vibrations and active breaking techniques for the Diastolic Timed Vibrator (DTV). DTV uses low frequency mechanical vibrations applied to the chest to help in clot dissolution in pre-hospitalization treatment of acute coronary ischemia. In this work, we argue that random and ramp type vibration patterns increase the performance of the DTV method. Furthermore, we present results for various methods of vibration stopping aiming at reduction of vibration overspill into the systole of heart cycle of the patient.