Ending the silent pandemic of unsafe abortion is an urgent public-health and human-rights imperative. As with other more visible global-health issues, this scourge threatens women throughout the ...developing world. Every year, about 19-20 million abortions are done by individuals without the requisite skills, or in environments below minimum medical standards, or both. Nearly all unsafe abortions (97%) are in developing countries. An estimated 68 000 women die as a result, and millions more have complications, many permanent. Important causes of death include haemorrhage, infection, and poisoning. Legalisation of abortion on request is a necessary but insufficient step toward improving women's health; in some countries, such as India, where abortion has been legal for decades, access to competent care remains restricted because of other barriers. Access to safe abortion improves women's health, and vice versa, as documented in Romania during the regime of President Nicolae Ceausescu. The availability of modern contraception can reduce but never eliminate the need for abortion. Direct costs of treating abortion complications burden impoverished health care systems, and indirect costs also drain struggling economies. The development of manual vacuum aspiration to empty the uterus, and the use of misoprostol, an oxytocic agent, have improved the care of women. Access to safe, legal abortion is a fundamental right of women, irrespective of where they live. The underlying causes of morbidity and mortality from unsafe abortion today are not blood loss and infection but, rather, apathy and disdain toward women. PUBLICATION ABSTRACT
The in situ oxygen partial pressure in normal and tumor tissues is in the range of a few percent. Therefore, when studying cell growth in 3D culture systems, it is essential to consider how the ...physiological oxygen concentration, rather than the one in the ambient air, influences the proliferation parameters. Here, we investigated the effect of reducing oxygen partial pressure from 21% to 5% on cell proliferation rate and regionalization in a 3D tumor spheroid model. We found that 5% oxygen concentration strongly inhibited spheroid growth, changed the proliferation gradient and reduced the 50% In Depth Proliferation index (IDP50), compared with culture at 21% oxygen. We then modeled the oxygen partial pressure profiles using the experimental data generated by culturing spheroids in physioxic and normoxic conditions. Although hypoxia occurred at similar depth in spheroids grown in the two conditions, oxygen partial pressure was a major rate-limiting factor with a critical effect on cell proliferation rate and regionalization only in spheroids grown in physioxic condition and not in spheroids grown at atmospheric normoxia. Our findings strengthen the need to consider conducting experiment in physioxic conditions (i.e., tissue normoxia) for proper understanding of cancer cell biology and the evaluation of anticancer drugs in 3D culture systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The avoidance of menstruation through continuous or extended (greater than 28 days) administration of combination hormonal contraceptives (CHCs) has gained legitimacy through its use in ...treating endometriosis, dysmenorrhea, and menstruation‐associated symptoms. Avoidance of menstruation through extended or continuous use of CHCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation‐related absenteeism from work or school.
Objectives
To determine the differences between continuous or extended‐cycle CHCs (pills, patch, ring) in regimens of greater than 28 days of active hormone compared with traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormones and 4 days of placebo). Our hypothesis was that continuous or extended‐cycle CHCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with standard cyclic CHCs.
Search methods
We updated our searches of the following databases to March 2023: EBM Review‐Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase.com, and LILACS. We searched ClinicalTrials.gov and the World Health Organization’s International Clinical Trials Registry Platform and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
Selection criteria
All randomized controlled trials in any language comparing continuous or extended‐cycle (greater than 28 days of active hormones) versus traditional cyclic administration (21 days of active hormones and 7 days of placebo, or 24 days of active hormones and 4 days of placebo) of CHCs for contraception.
Data collection and analysis
Titles and s identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 5. Peto odds ratios with 95% confidence intervals were calculated for all outcomes for dichotomous outcomes. Weighted mean difference was calculated for continuous outcomes. The trials were critically appraised by examining the following factors: study design, blinding, randomization method, group allocation concealment, exclusions after randomization, loss to follow‐up, and early discontinuation. Because the included trials did not have a standard treatment (type of CHC formulation, route of delivery, or time length for continuous dosing), we could not aggregate data into meta‐analysis.
Main results
Twelve randomized controlled trials met our inclusion criteria. Study findings were similar between 28‐day and extended or continuous regimens in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28‐day and extended or continuous cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group. The studies that reported menstrual symptoms found that the extended or continuous group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Eleven out of the twelve studies found that bleeding patterns were either equivalent between groups or improved with extended or continuous cycles over time. Endometrial lining assessments by ultrasound and/or endometrial biopsy were done in some participants and were all normal after cyclic or extended CHC use.
Authors' conclusions
The 2014 update yielded four additional trials but unchanged conclusions. Evidence from existing randomized control trials comparing continuous or extended‐cycle CHCs (greater than 28 days of active combined hormones) to traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormone and 4 days of placebo) is of good quality. However, the variations in type of hormones and time length for extended‐cycle dosing make a formal meta‐analysis impossible. Future studies should choose a previously described type of CHC and dosing regimen. More attention needs to be directed towards participant satisfaction, continuation, and menstruation‐associated symptoms.
Combination contraceptives: effects on weight Gallo, Maria F; Lopez, Laureen M; Grimes, David A ...
Cochrane database of systematic reviews,
01/2014, Letnik:
2014, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit ...the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established.
Objectives
The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight.
Search methods
In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search.
Selection criteria
All English‐language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length.
Data collection and analysis
All titles and s located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post‐treatment measurements using a fixed‐effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated.
Main results
We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight change. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight change did not differ between groups where this was studied.
Authors' conclusions
Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non‐hormonal group to control for other factors, including changes in weight over time.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are among the most frequently prescribed groups of drugs worldwide. The use of NSAIDs is associated with a high number ...of significant adverse effects. Recently, the safety of PPIs has also been challenged. Capsule endoscopy studies reveal that even low-dose NSAIDs are responsible for gut mucosal injury and numerous clinical adverse effects, for example, bleeding and anemia, that might be difficult to diagnose. The frequent use of PPIs can exacerbate NSAID-induced small intestinal injury by altering intestinal microbiota. Thus, the use of PPI is considered to be an independent risk factor associated with NSAID-associated enteropathy. In this review, we discuss this important clinical problem and review relevant aspects of epidemiology, pathophysiology, and management. We also present the hypothesis that even minor and subclinical injury to the intestinal mucosa can result in significant, though delayed, metabolic consequences, which may seriously affect the health of an individual. PubMed was searched using the following key words (each key word alone and in combination): gut microbiota, microbiome, non-steroidal anti inflammatory drugs, proton pump inhibitors, enteropathy, probiotic, antibiotic, mucosal injury, enteroscopy, and capsule endoscopy. Google engine search was also carried out to identify additional relevant articles. Both original and review articles published in English were reviewed.
INTRODUCTION:Combined oral contraceptives containing norethindrone acetate (NETA) are widely used in the US and globally, but how they compare to levonorgestrel-containing pills is unknown. This ...pooled analysis compares the safety of NETA and levonorgestrel (LNG) in pills with ethinyl estradiol (EE) ≤30 mcg.
METHODS:We pooled cohorts of NETA (EE ≤30 mcg) and LNG (EE ≤30 mcg) users from four large prospective, controlled, non-interventional, cohort studies in 14 European countries, US and Canada. Baseline characteristics, including reproductive, contraceptive and medical history, were summarized using descriptive statistics. Propensity score sub-classification was applied to balance baseline characteristics between cohorts. Time-to-event analysis of venous and arterial thromboembolic events was carried out based on the extended Cox model to calculate crude and adjusted hazard ratios with 95% confidence intervals.
RESULTS:Approximately 80,000 women contributed 145,000 women years of exposure. The prevalence of prognostic factors at baseline showed typical features of US and European oral contraceptive users. A comparison between NETA vs LNG showed no significant difference in the risk of venous thromboembolismadjusted hazard ratio 0.73 (95% CI 0.48-1.11). A similar result was observed considering the risk of arterial thromboembolism (adjusted hazard ratio 0.89 95% CI 0.42-1.89).
CONCLUSION:Low-dose oral contraceptives containing NETA and LNG are associated with similar low risks of venous and arterial disease. This analysis provides reassurance for both women and clinicians regarding the safety of contemporary oral contraceptives.
Unsafe abortion: the preventable pandemic Grimes, David A; Benson, Janie; Singh, Susheela ...
The Lancet (British edition),
11/2006, Letnik:
368, Številka:
9550
Journal Article
Recenzirano
Ending the silent pandemic of unsafe abortion is an urgent public-health and human-rights imperative. As with other more visible global-health issues, this scourge threatens women throughout the ...developing world. Every year, about 19–20 million abortions are done by individuals without the requisite skills, or in environments below minimum medical standards, or both. Nearly all unsafe abortions (97%) are in developing countries. An estimated 68 000 women die as a result, and millions more have complications, many permanent. Important causes of death include haemorrhage, infection, and poisoning. Legalisation of abortion on request is a necessary but insufficient step toward improving women's health; in some countries, such as India, where abortion has been legal for decades, access to competent care remains restricted because of other barriers. Access to safe abortion improves women's health, and vice versa, as documented in Romania during the regime of President Nicolae Ceausescu. The availability of modern contraception can reduce but never eliminate the need for abortion. Direct costs of treating abortion complications burden impoverished health care systems, and indirect costs also drain struggling economies. The development of manual vacuum aspiration to empty the uterus, and the use of misoprostol, an oxytocic agent, have improved the care of women. Access to safe, legal abortion is a fundamental right of women, irrespective of where they live. The underlying causes of morbidity and mortality from unsafe abortion today are not blood loss and infection but, rather, apathy and disdain toward women.
•Rainfall-runoff model driven using ensemble satellite rainfall inputs.•Study area is operational proxy for a semi-arid, poorly instrumented catchment.•Model calibrated using a novel ensemble-wise ...method – EnsALL.•Ensemble wise method produced more robust calibrations than deterministic methods.•Metrics adapted from ensemble forecast verification used for analysis.
The potential for satellite rainfall estimates to drive hydrological models has been long understood, but at the high spatial and temporal resolutions often required by these models the uncertainties in satellite rainfall inputs are both significant in magnitude and spatiotemporally autocorrelated. Conditional stochastic modelling of ensemble observed fields provides one possible approach to representing this uncertainty in a form suitable for hydrological modelling. Previous studies have concentrated on the uncertainty within the satellite rainfall estimates themselves, sometimes applying ensemble inputs to a pre-calibrated hydrological model. This approach does not account for the interaction between input uncertainty and model uncertainty and in particular the impact of input uncertainty on model calibration. Moreover, it may not be appropriate to use deterministic inputs to calibrate a model that is intended to be driven by using an ensemble. A novel whole-ensemble calibration approach has been developed to overcome some of these issues.
This study used ensemble rainfall inputs produced by a conditional satellite-driven stochastic rainfall generator (TAMSIM) to drive a version of the Pitman rainfall-runoff model, calibrated using the whole-ensemble approach. Simulated ensemble discharge outputs were assessed using metrics adapted from ensemble forecast verification, showing that the ensemble outputs produced using the whole-ensemble calibrated Pitman model outperformed equivalent ensemble outputs created using a Pitman model calibrated against either the ensemble mean or a theoretical infinite-ensemble expected value.
Overall, for the verification period the whole-ensemble calibration provided a mean RMSE of 61.7% of the mean wet season discharge, compared to 83.6% using a calibration based on the daily mean of the ensemble estimates. Using a Brier’s Skill Score to assess the performance of the ensemble against a climatic estimate, the whole-ensemble calibration provided a positive score for the main range of discharge events. The equivalent score for calibration against the ensemble mean was negative, indicating it showed no skill versus the climatic estimate.
The reality that volumes of published biomedical research are not reproducible is an increasingly recognized problem. Spurious results reduce trustworthiness of reported science, increasing research ...waste. While science should be self-correcting from a philosophical perspective, that in insolation yields no information on efforts required to nullify suspect findings or factors shaping how quickly science may be corrected. There is also a paucity of information on how perverse incentives in the publishing ecosystem favouring novel positive findings over null results shape the ability of published science to self-correct. Knowledge of factors shaping self-correction of science remain obscure, limiting our ability to mitigate harms. This modelling study introduces a simple model to capture dynamics of the publication ecosystem, exploring factors influencing research waste, trustworthiness, corrective effort and time to correction. Results from this work indicate that research waste and corrective effort are highly dependent on field-specific false positive rates and time delays to corrective results to spurious findings are propagated. The model also suggests conditions under which biomedical science is self-correcting and those under which publication of correctives alone cannot stem propagation of untrustworthy results. Finally, this work models a variety of potential mitigation strategies, including researcher- and publisher-driven interventions.
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