Summary
Objective
Women with pre‐eclampsia have elevated circulating levels of soluble fms‐like tyrosine kinase‐1 (sFlt‐1). Statins can reduce sFlt‐1 from cultured cells and improve pregnancy outcome ...in animals with a pre‐eclampsia‐like syndrome. We investigated the effect of pravastatin on plasma sFlt‐1 levels during pre‐eclampsia.
Design
Blinded (clinician and participant), proof of principle, placebo‐controlled trial.
Setting
Fifteen UK maternity units.
Population
We used a minimisation algorithm to assign 62 women with early‐onset pre‐eclampsia (24+0–31+6 weeks of gestation) to receive pravastatin 40 mg daily (n = 30) or matched placebo (n = 32), from randomisation to childbirth.
Primary outcome
Difference in mean plasma sFlt‐1 levels over the first 3 days following randomisation.
Results
The difference in the mean maternal plasma sFlt‐1 levels over the first 3 days after randomisation between the pravastatin (n = 27) and placebo (n = 29) groups was 292 pg/ml (95% CI −1175 to 592; P = 0.5), and over days 1–14 was 48 pg/ml (95% CI −1009 to 913; P = 0.9). Women who received pravastatin had a similar length of pregnancy following randomisation compared with those who received placebo (hazard ratio 0.84; 95% CI 0.50–1.40; P = 0.6). The median time from randomisation to childbirth was 9 days (interquartile range IQR 5–14 days) for the pravastatin group and 7 days (IQR 4–11 days) for the placebo group. There were three perinatal deaths in the placebo‐treated group and no deaths or serious adverse events attributable to pravastatin.
Conclusions
We found no evidence that pravastatin lowered maternal plasma sFlt‐1 levels once early‐onset pre‐eclampsia had developed. Pravastatin appears to have no adverse perinatal effects.
Tweetable
Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds.
Tweetable
Pravastatin does not improve maternal plasma sFlt‐1 or placental growth factor levels following a diagnosis of early preterm pre‐eclampsia #clinicaltrial finds.
This book seeks to answer why there has there been a persistent fascination by the sighted, including philosophers, poets and the public, in what the blind 'see'.
Thanks to ready access to hydrogen breath testing, small intestinal bacterial overgrowth (SIBO) is now commonly diagnosed among individuals presenting with a variety of gastrointestinal and even ...nongastrointestinal symptoms and is increasingly implicated in lay press and media in the causation of a diverse array of disorders. Its definition, however, remains controversial and true prevalence, accordingly, undefined. The purpose of this review, therefore, was to provide a historical background to the concept of SIBO, critically review current concepts of SIBO (including symptomatology, pathophysiology, clinical consequences, diagnosis and treatment), define unanswered questions and provide a road map toward their resolution.
Best Practice Advice statements were developed following discussion by the 3 authors. Two authors each developed text around certain Best Practice Advice based on a review of available literature. All 3 authors reviewed the complete draft and after discussion, redrafting, and further review and revision, all of the authors agreed on a final draft.
The definition of SIBO as a clinical entity lacks precision and consistency; it is a term generally applied to a clinical disorder where symptoms, clinical signs, and/or laboratory abnormalities are attributed to changes in the numbers of bacteria or in the composition of the bacterial population in the small intestine.
Symptoms traditionally linked to SIBO include bloating, diarrhea, and abdominal pain/discomfort. Steatorrhea may be seen in more severe cases.
There is insufficient evidence to support the use of inflammatory markers, such as fecal calprotectin to detect SIBO.
Laboratory findings can include elevated folate and, less commonly, vitamin B-12 deficiency, or other nutritional deficiencies.
A major impediment to our ability to accurately define SIBO is our limited understanding of normal small intestinal microbial populations—progress in sampling technology and techniques to enumerate bacterial populations and their metabolic products should provide much needed clarity.
Controversy remains concerning the role of SIBO in the pathogenesis of common functional symptoms, such as those regarded as components of irritable bowel syndrome.
Management should focus on the identification and correction (where possible) of underlying causes, correction of nutritional deficiencies, and the administration of antibiotics. This is especially important for patients with significant maldigestion and malabsorption.
Although irritable bowel syndrome has been shown to respond to therapy with a poorly absorbed antibiotic, the role of SIBO or its eradication in the genesis of this response warrants further confirmation in randomized controlled trials.
There is a limited database to guide the clinician in developing antibiotic strategies for SIBO, in any context. Therapy remains, for the most part, empiric but must be ever mindful of the potential risks of long-term broad-spectrum antibiotic therapy.
Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex ...intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There...
We conducted a systematic review and meta-analysis to compare the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with irritable bowel syndrome (IBS) and controls.
Electronic ...databases were searched up to December 2018 for studies reporting SIBO prevalence in patients with IBS. Prevalence rates, odds ratios (ORs), and 95% confidence intervals (CIs) of SIBO in patients with IBS and controls were calculated.
We included 25 studies with 3,192 patients with IBS and 3,320 controls. SIBO prevalence in patients with IBS was significantly increased compared with controls (OR = 3.7, 95% CI 2.3-6.0). In studies using only healthy controls, the OR for SIBO in patients with IBS was 4.9 (95% CI 2.8-8.6). With breath testing, SIBO prevalence in patients with IBS was 35.5% (95% CI 33.6-37.4) vs 29.7% (95% CI 27.6-31.8) in controls. Culture-based studies yielded a SIBO prevalence of 13.9% (95% CI 11.5-16.4) in patients with IBS and 5.0% (95% CI 3.9-6.2) in controls with a cutoff value of 10 colony-forming units per milliliter vs 33.5% (95% CI 30.1-36.9) in patients with IBS and 8.2% (95% CI 6.8-9.6) in controls with a cutoff value of 10 colony-forming unit per milliliter, respectively. SIBO prevalence diagnosed by lactulose breath test is much greater in both patients with IBS (3.6-fold) and controls (7.6-fold) compared with glucose breath test. Similar difference is seen when lactulose breath test is compared with culture methods. OR for SIBO in patients with IBS-diarrhea compared with IBS-constipation was 1.86 (95% CI 1.83-2.8). Methane-positive breath tests were significantly more prevalent in IBS-constipation compared with IBS-diarrhea (OR = 2.3, 95% CI 1.2-4.2). In patients with IBS, proton pump inhibitor was not associated with SIBO (OR = 0.8, 95% CI 0.5-1.5, P = 0.55).
This systematic review and meta-analysis suggests a link between IBS and SIBO. However, the overall quality of the evidence is low. This is mainly due to substantial "clinical heterogeneity" due to lack of uniform selection criteria for cases and controls and limited sensitivity and specificity of the available diagnostic tests.
Small intestinal bacterial overgrowth (SIBO), characterized by the presence of excessive bacteria in the small intestine, is typically described as a malabsorptive syndrome occurring in the context ...of gut stasis syndromes. SIBO is now considered to be a disorder associated with diverse clinical conditions without classic risk factors for SIBO and a cause of several nonspecific gastrointestinal and nongastrointestinal symptoms. Because there is currently no gold standard for diagnosing SIBO, its prevalence and role in the pathogenesis of other diseases remain uncertain; as does optimal treatment of patients with relapsing symptoms.
Understanding Blind Deconvolution Algorithms Levin, A.; Weiss, Y.; Durand, F. ...
IEEE transactions on pattern analysis and machine intelligence,
12/2011, Volume:
33, Issue:
12
Journal Article
Peer reviewed
Blind deconvolution is the recovery of a sharp version of a blurred image when the blur kernel is unknown. Recent algorithms have afforded dramatic progress, yet many aspects of the problem remain ...challenging and hard to understand. The goal of this paper is to analyze and evaluate recent blind deconvolution algorithms both theoretically and experimentally. We explain the previously reported failure of the naive MAP approach by demonstrating that it mostly favors no-blur explanations. We show that, using reasonable image priors, a naive simulations MAP estimation of both latent image and blur kernel is guaranteed to fail even with infinitely large images sampled from the prior. On the other hand, we show that since the kernel size is often smaller than the image size, a MAP estimation of the kernel alone is well constrained and is guaranteed to succeed to recover the true blur. The plethora of recent deconvolution techniques makes an experimental evaluation on ground-truth data important. As a first step toward this experimental evaluation, we have collected blur data with ground truth and compared recent algorithms under equal settings. Additionally, our data demonstrate that the shift-invariant blur assumption made by most algorithms is often violated.
Peer review may be “single-blind,” in which reviewers are aware of the names and affiliations of paper authors, or “double-blind,” in which this information is hidden. Noting that computer science ...research often appears first or exclusively in peer-reviewed conferences rather than journals, we study these two reviewing models in the context of the 10th Association for Computing Machinery International Conference on Web Search and Data Mining, a highly selective venue (15.6% acceptance rate) in which expert committee members review full-length submissions for acceptance. We present a controlled experiment in which four committee members review each paper. Two of these four reviewers are drawn from a pool of committee members with access to author information; the other two are drawn from a disjoint pool without such access. This information asymmetry persists through the process of bidding for papers, reviewing papers, and entering scores. Reviewers in the single-blind condition typically bid for 22% fewer papers and preferentially bid for papers from top universities and companies. Once papers are allocated to reviewers, single-blind reviewers are significantly more likely than their double-blind counterparts to recommend for acceptance papers from famous authors, top universities, and top companies. The estimated odds multipliers are tangible, at 1.63, 1.58, and 2.10, respectively.
Use of oral live-attenuated polio vaccines (OPV), and injected inactivated polio vaccines (IPV) has almost achieved global eradication of wild polio viruses. To address the goals of achieving and ...maintaining global eradication and minimising the risk of outbreaks of vaccine-derived polioviruses, we tested novel monovalent oral type-2 poliovirus (OPV2) vaccine candidates that are genetically more stable than existing OPVs, with a lower risk of reversion to neurovirulence. Our study represents the first in-human testing of these two novel OPV2 candidates. We aimed to evaluate the safety and immunogenicity of these vaccines, the presence and extent of faecal shedding, and the neurovirulence of shed virus.
In this double-blind, single-centre phase 1 trial, we isolated participants in a purpose-built containment facility at the University of Antwerp Hospital (Antwerp, Belgium), to minimise the risk of environmental release of the novel OPV2 candidates. Participants, who were recruited by local advertising, were adults (aged 18–50 years) in good health who had previously been vaccinated with IPV, and who would not have any contact with immunosuppressed or unvaccinated people for the duration of faecal shedding at the end of the study. The first participant randomly chose an envelope containing the name of a vaccine candidate, and this determined their allocation; the next 14 participants to be enrolled in the study were sequentially allocated to this group and received the same vaccine. The subsequent 15 participants enrolled after this group were allocated to receive the other vaccine. Participants and the study staff were masked to vaccine groups until the end of the study period. Participants each received a single dose of one vaccine candidate (candidate 1, S2/cre5/S15domV/rec1/hifi3; or candidate 2, S2/S15domV/CpG40), and they were monitored for adverse events, immune responses, and faecal shedding of the vaccine virus for 28 days. Shed virus isolates were tested for the genetic stability of attenuation. The primary outcomes were the incidence and type of serious and severe adverse events, the proportion of participants showing viral shedding in their stools, the time to cessation of viral shedding, the cell culture infective dose of shed virus in virus-positive stools, and a combined index of the prevalence, duration, and quantity of viral shedding in all participants. This study is registered with EudraCT, number 2017-000908-21 and ClinicalTrials.gov, number NCT03430349.
Between May 22 and Aug 22, 2017, 48 volunteers were screened, of whom 15 (31%) volunteers were excluded for reasons relating to the inclusion or exclusion criteria, three (6%) volunteers were not treated because of restrictions to the number of participants in each group, and 30 (63%) volunteers were sequentially allocated to groups (15 participants per group). Both novel OPV2 candidates were immunogenic and increased the median blood titre of serum neutralising antibodies; all participants were seroprotected after vaccination. Both candidates had acceptable tolerability, and no serious adverse events occurred during the study. However, severe events were reported in six (40%) participants receiving candidate 1 (eight events) and nine (60%) participants receiving candidate 2 (12 events); most of these events were increased blood creatinine phosphokinase but were not accompanied by clinical signs or symptoms. Vaccine virus was detected in the stools of 15 (100%) participants receiving vaccine candidate 1 and 13 (87%) participants receiving vaccine candidate 2. Vaccine poliovirus shedding stopped at a median of 23 days (IQR 15–36) after candidate 1 administration and 12 days (1–23) after candidate 2 administration. Total shedding, described by the estimated median shedding index (50% cell culture infective dose/g), was observed to be greater with candidate 1 than candidate 2 across all participants (2·8 95% CI 1·8–3·5 vs 1·0 0·7–1·6). Reversion to neurovirulence, assessed as paralysis of transgenic mice, was low in isolates from those vaccinated with both candidates, and sequencing of shed virus indicated that there was no loss of attenuation in domain V of the 5ʹ-untranslated region, the primary site of reversion in Sabin OPV.
We found that the novel OPV2 candidates were safe and immunogenic in IPV-immunised adults, and our data support the further development of these vaccines to potentially be used for maintaining global eradication of neurovirulent type-2 polioviruses.
Bill & Melinda Gates Foundation.
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