The paradigm of norgestimate: a third-generation testosterone-derivative progestin with a peripheral anti-androgenic activity and the lowest risk of venous thromboembolism

Introduction: Norgestimate (NGM) is a testosterone derivative with peculiar receptor activities. Areas covered: This is a narrative review of the available data on the pharmacotherapy of NGM in combined hormonal contraceptives (CHCs) in terms of contraceptive efficacy, venous thromboembolism (VTE) risk, safety, tolerability and bleeding patterns. A comprehensive literature review was conducted in August 2020 using PubMed with the keyword ‘norgestimate’. Expert Opinion: NGM shows a mild estrogenic activity associated with anti-mineralocorticoid and anti-androgenic properties, largely responsible for the cardiovascular safety profile. The anti-androgenic property depends on the androgen receptor (AR) nuclear translocation (AR trafficking and its subnuclear distribution), the inhibition of 5α-reductase activity (it possesses higher activity compared to other available progestins), and the increase on sexual hormone binding globulin (SHBG) levels if combined with an estrogenic counterpart. NGM is one of the molecules that best modulates the power of ethinyl-estradiol on the thromboembolic risk, being associated with the lowest VTE risk between different CHCs. NGM has the advantage of retaining peripheral anti-androgenic activity, demonstrated by the impact on lipid and glucose metabolism, and it should be preferred if compared with other similar progestins of the same class of risk which are much more androgenic, such as levonorgestrel

Emerging ethical issues regarding digital health data on the world medical association draft declaration on ethical considerations regarding health databases and biobanks

This is the final version of the article. Available from the publisher via the DOI in this record.All authors are affiliated with the Data and IT in Health and Medicine Lab which is coordinated at the Department of Social Science, Health & Medicine, King’s College London (datahealthmedicine.wordpress.com). This article builds upon a response submitted by the Lab to the World Medical Association consultation on the draft Declaration on Ethical Considerations regarding Health Databases and Biobanks in June 2015. DOI: 10.13140/RG.2.1.3334.4163. Barbara Prainsack is a member of the Navigating Knowledge Landscapes (NKL) network led by Anna Lydia Svalastog (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4576744/)

The impact of COVID-19 lockdown on admission to gynecological emergency departments: Results from a multicenter Italian study

Objective: To evaluate the impact of the COVID-19 lockdown on admissions to gynecological emergency departments (ED) of three Italian university hospitals with different rates of COVID-19 incidence. Methods: A retrospective study was conducted in the gynecological EDs of Modena (Emilia-Romagna), Sassari and Cagliari (Sardinia) regarding all admissions to gynecological EDs during November 1 to 30, 2019, and March 11 to April 9, 2020 (lockdown period). Results: A total of 691 women (mean age 38.3 \ub1 14.3 years) who were admitted to the gynecological EDs were included. The relative decrease in women evaluated from March 11 to April 9, 2020, was 1256.6% (95% confidence interval [CI] 52.2\u201361.1). Time spent in the ED was also significantly shorter during this period (P=0.02) in comparison to November 1 to 30, 2019. The most evident decrease was observed for pelvic pain ( 1268.9% [95% CI 60.3\u201376.7]; 1291 cases). The management of women suggests a more effective use of the ED, with higher rates of hospitalization (P=0.001) and recourse to emergent surgeries (P=0.005) and lower rates of discharge to home (P=0.03). Conclusion: The COVID-19 lockdown greatly reduced the rate of admission to gynecological EDs, but the real emergencies were filtered from the more deferrable ones

The motivation for citizens’ involvement in life sciences research is predicted by age and gender

Open Science is an umbrella term encompassing multiple concepts as open access to publications, open data, open education and citizen science that aim to make science more open and transparent. Citizen science, an important facet of Open Science, actively involves nonscientists in the research process, and can potentially be beneficial for multiple actors, such as scientists, citizens, policymakers and society in general. However, the reasons that motivate different segments of the public to participate in research are still understudied. Therefore, based on data gathered from a survey conducted in Czechia, Germany, Italy, Spain, Sweden, and the UK (N = 5,870), this study explores five types of incentives that can motivate individuals to become involved in life sciences research. The results demonstrate that men and younger individuals are more persuaded by extrinsic motives (external benefits or rewards), as compared with women and older people, who are driven by intrinsic motives (that originates from within an individual). This paper shows that specific strata of the population are differentially motivated to engage in research, thereby providing relevant knowledge for effectively designing public involvement activities that target various groups of the public in research projects

Digital orphans: Data closure and openness in patient- powered networks

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this record.In this paper, we discuss an issue linked to data-sharing regimes in patient-powered, social-media-based networks, namely that most of the data that patient users share are not used to research scientific issues or the patient voice. This is not a trivial issue, as participation in these networks is linked to openness in data sharing, which would benefits fellow patients and contributes to the public good more generally. Patient-powered research networks are often framed as disrupting research agendas and the industry. However, when data that patients share are not accessible for research, their epistemic potential is denied. The problem is linked to the business models of the organisations managing these networks: models centred on controlling patient data tend to close networks with regard to data use. The constraint on research is at odds with the ideals of a sharing, open and supportive epistemic community that networks’ own narratives evoke. This kind of failure can create peculiar scenarios, such as the emergence of the ‘digital orphans’ of Internet research. By pointing out the issue of data use, this paper informs the discussion about the capacity of patient-powered networks to support research participation and the patient voice.We are indebted to the anonymous reviewers and the editor, who with their supportive and constructive comments helped us to better clarify and highlight the argument of the article. We would like to also thank friends and colleagues who have offered valuable comments and suggestions on early drafts of this paper. We would like to especially thank Barbara Prainsack, Sabina Leonelli, Alena Buyx, and David Teira. This research is funded by the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement number 335925, and the German Federal Ministry of Education and Research (grant number 01GP1311

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Drospirenone 4 mg-only pill (DOP) in 24+4 regimen: a new option for oral contraception

Introduction: The use of progestin-only pills (POPs) is still relatively infrequent, mainly for their unpredictable effect on menstrual bleeding. A new POP consisting of 4 mg drospirenone (DRSP) for 24 days plus 4-day hormone-free interval has been developed to address this need. DRSP is a potent progestin analogue of spironolactone, with antiandrogenic and antimineralocorticoid properties. Areas covered: This is a narrative review of the available data on the pharmacotherapy of the new DRSP-only pill. The research includes aspects of pharmacokinetics/pharmacodynamics of the compound: the main focus is on the clinical effects of DRSP-only pill in terms of contraceptive efficacy, haemostatic effect, safety, tolerability and bleeding patterns. Expert Opinion: The DRSP-only pill presents a similar Pearl Index to that of common combined hormonal contraceptives: it is a POP with a better bleeding profile than traditional POPs (higher rates of scheduled bleedings and much lower rates of unscheduled intracyclic bleeding/spotting) which could increase its acceptability and the panorama of possible users. For these reasons, DRSP-only pill represents a real step forward in oral contraception with only progestins, even if the bleeding patterns during its use are still different to oestrogen-containing products (i.e. lower rates of scheduled bleedings and higher rate of amenorrhea)

Contemporary prescriptions pattern of different dose levonorgestrel-releasing intrauterine systems in an Italian service for family planning

Objective: Current research informations fail to adequately inform about when levonorgestrel-releasing intrauterine system (LNG-IUS) 52 mg is used instead of other lower dose LNG-IUSs (13.5 and 19.5 mg) and other long-acting reversible contraceptives (LARCs) in clinical practice. Methods: A retrospective cohort study was performed in a third-level Service for Family Planning of Modena University hospital about all the first modern contraceptives prescriptions in the whole year 2019 performed by the same group of physicians. All women included underwent a detailed transvaginal ultrasound (TVUS) at prescription and a second evaluation within 3 months when they were still using the prescribed method. Results: To 69/160 (43.1%) women a short-acting reversible contraceptive (SARC), while to 91/160 (56.9%) a LARC was prescribed. Women with a LARC prescription were older than them with a short-acting (SARC) (p <.0001). Women with LNG-IUS 52 mg prescription were significantly the oldest (42.9 ± 5.3), while those with intrauterine copper device and lower dose LNG-IUS were of similar age (36.5 ± 7.3 and 34.9 ± 2.3), significantly lower (p <.005). Women with implant prescription had the same age as SARC, being the youngest (30.7 ± 8.9 and 31.0 ± 9.5) (p <.0001). Women with LNG-IUS 52 mg prescription mg presented with bigger uterine volume (p =.001). In multivariate analyses, the LNG-IUS 52 mg prescription was significantly linked only to age (OR 1.24; 95% CI 1.11–1.37, p <.0001) and presence of adenomyosis (OR 4.56; 95% CI 1.45-14.33, p =.009). Conclusions: The use of LNG-IUS 52 mg instead of other LARCs is preferred for older women, with uteri of increased volume due to adenomyosis, suggesting a possible differential use of available LNG-IUSs in the contemporary clinical practice