The objectives of this study were to determine the prevalence of carriage of ESBL-producing Enterobacteriaceae (ESBL-E) in a representative sample of the general adult Dutch community, to identify ...risk factors and to gain understanding of the epidemiology of these resistant strains.
Adults enrolled in five general practices in Amsterdam were approached by postal mail and asked to fill in a questionnaire and to collect a faecal sample. Samples were analysed for the presence of ESBL-E. ESBL genes were characterized by PCR and sequencing. Strains were typed using MLST and amplified fragment length polymorphism (AFLP) and plasmids were identified by PCR-based replicon typing. Risk factors for carriage were investigated by multivariate analysis.
ESBL-E were found in 145/1695 (8.6%) samples; 91% were Escherichia coli. Most ESBL genes were of the CTX-M group (blaCTX-M-1 and blaCTX-M-15). MLST ST131 was predominant and mainly associated with CTX-M-15-producing E. coli. One isolate with reduced susceptibility to ertapenem produced OXA-48. In multivariate analyses, use of antimicrobial agents, use of antacids and travel to Africa, Asia and Northern America were associated with carriage of ESBL-E, in particular strains with blaCTX-M-14/15.
This study showed a high prevalence of ESBL-E carriage in the general Dutch community. Also, outside hospitals, the use of antibiotics was a risk factor; interestingly, use of antacids increased the risk of carriage. A major risk factor in the general population was travel to countries outside Europe, in particular to Asia, Africa and Northern America.
To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli, as ...risk factors for ESBL E. coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with those of previous studies.
Population-based case–control study including 339 cases with community-onset ESBL E. coli UTI in 2007–2012, 3390 non-ESBL E. coli UTI controls and 3390 population controls. We investigated potential risk factors by estimating ORs and 95% CIs adjusting for sex, age and co-morbidity.
Comparing cases with non-ESBL E. coli UTI, PPI use yielded an OR of 1.6 (95% CI 1.2–2.0) and antibiotic exposure gave an OR of 1.4 (95% CI 1.1–1.8); these were driven by nitrofurantoin (OR 1.8; 95% CI 1.3–2.6) and macrolides (OR 1.7; 95% CI 1.2–2.3). Other risk factors included previous hospitalization with one or two and more than two hospitalizations versus none yielding ORs of 1.9 (95% CI 1.4–2.5) and 4.6 (95% CI 3.2–6.8), recent surgery (OR 2.0; 95% CI 1.5–2.8), renal disease (OR 2.2; 95% CI 1.4–3.4), chronic pulmonary disease (OR 1.4; 95% CI 1.0–2.0) and cancer (OR 1.5; 95% CI 1.1–2.1). Comparing cases with population controls, we found that most risk factors were also risk factors for non-ESBL UTI.
ESBL E. coli UTI were associated with previous hospitalization and surgery. Nitrofurantoin and macrolides augmented the risk. PPIs had a moderate effect but may be important facilitators of ESBL carriage due to their widespread use.
Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome. Whether acid suppression increases the risk of colonization with multidrug-resistant microorganisms (MDROs) is ...unclear.
To systematically examine the association of use of acid suppressants with the risk of colonization with MDROs and to perform a meta-analysis of current evidence.
PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from database inception through July 8, 2019.
Study selection was performed independently by 2 authors (R.P.J.W. and C.M.J.E.V.-G.) on the basis of predefined selection criteria; conflicts were resolved by consensus or by an adjudicator (K.v.D.). Human observational studies (case control, cohort, and cross-sectional) and clinical trial designs were selected if they quantified the risk of MDRO colonization in users of acid suppressants in comparison with nonusers.
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. Data were extracted independently by the same 2 authors, and adjudication was conducted when necessary. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were estimated using random-effects models; heterogeneity was evaluated using the I2 method.
The primary outcome measure was intestinal colonization with MDROs of the Enterobacterales order (producing extended-spectrum β-lactamases, carbapenemases, or plasmid-mediated AmpC β-lactamases), vancomycin-resistant enterococci, methicillin-resistant or vancomycin-resistant Staphylococcus aureus, or multidrug-resistant Pseudomonas or Acinetobacter species.
A total of 26 observational studies including 29 382 patients (11 439 38.9% acid suppressant users) met the selection criteria. Primary meta-analysis of 12 studies including 22 305 patients that provided adjusted ORs showed that acid suppression increased the odds of intestinal carriage of MDROs of the Enterobacterales order and of vancomycin-resistant enterococci by roughly 75% (OR = 1.74; 95% CI, 1.40-2.16; I2 = 68%). The odds were concordant with the secondary pooled analysis of all 26 studies (OR = 1.70; 95% CI, 1.44-1.99; I2 = 54%). Heterogeneity was partially explained by variations in study setting and the type of acid suppression.
Acid suppression is associated with increased odds of MDRO colonization. Notwithstanding the limitations of observational studies, the association is plausible and is strengthened by controlling for confounders. In view of the global increase in antimicrobial resistance, stewardship to reduce unnecessary use of acid suppressants may help to prevent MDRO colonization.
Mortality in Acromegaly: A Metaanalysis Dekkers, O. M; Biermasz, N. R; Pereira, A. M ...
The journal of clinical endocrinology and metabolism,
01/2008, Letnik:
93, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Context: Several studies have assessed mortality risk in patients treated for acromegaly. All studies found a mortality that was higher than expected for the general population, but most of these ...increases were not statistically significant. For this reason, it is not formally established whether mortality in acromegaly is different from the general population.
Objective: The objective of the study was to address the all-cause mortality risk in patients with acromegaly.
Design: The study was a metaanalysis.
Methods: Sixteen studies on mortality in patients with acromegaly were included. The principal outcome of the metaanalysis was the weighted average of the standardized mortality ratio (SMR) of all studies. In addition, we performed a subgroup analysis of studies in which more than 80% of the patients were treated by transsphenoidal approach.
Results: The weighted mean of the SMR from all 16 studies was 1.72 (95% confidence interval 1.62–1.83). In studies with transsphenoidal surgery as the primary therapy, the weighted mean of the SMR was 1.32 (95% confidence interval 1.12–1.56).
Conclusions: This metaanalysis shows increased all-cause mortality in acromegalic patients, compared with the general population, even after transsphenoidal surgery.
Case reports and case series have their own role in the progress of medical science. They permit discovery of new diseases and unexpected effects (adverse or beneficial) as well as the study of ...mechanisms, and they play an important role in medical education. Case reports and series have a high sensitivity for detecting novelty and therefore remain one of the cornerstones of medical progress; they provide many new ideas in medicine. At the same time, good case reporting demands a clear focus to make explicit to the audience why a particular observation is important in the context of existing knowledge.
Carriers of multidrug-resistant bacteria are at risk of infections with these bacteria; the precise size of this risk is unclear. We aimed to quantify the effect of gut colonisation on subsequent ...risk of infection with multidrug-resistant bacteria.
We performed a systematic review and meta-regression analysis. We searched PubMed, Embase, Web of Science Core Collection, and Google Scholar for follow-up studies published from Jan 1, 1995, to March 17, 2022, that measured the incidence of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and from Jan 1, 1995, to March 15, 2022, that measured the incidence of infections with vancomycin-resistant enterococci (VRE). We included original cohort studies and case-control studies that used incidence-density sampling, included 50 or more patients with enteric colonisation or positive urinary samples as a surrogate marker of colonisation, or both, and analysed infections clearly preceded by colonisation. We did not use any language restrictions. We excluded studies not reporting length of follow-up. Summary data were extracted and independently cross-verified by two authors. Carriage was defined as MDR-GNB or VRE, detected in faecal or urinary cultures. Our primary outcomes were cumulative incidence and incidence density of infection in patients colonised by multidrug-resistant bacteria. To estimate pooled incidences, general linearised mixed-effects meta-regressions were used, adjusting for varying follow-up durations. This study is registered with PROSPERO, CRD42020222415.
Of the 301 studies identified, 44 studies (26 on MDR-GNB, 14 on VRE, and four on both MDR-GNB and VRE) from 14 countries were retained for qualitative synthesis, 40 of which were analysed with meta-regression, comprising data for 14 049 patients colonised with multidrug-resistant bacteria. The pooled cumulative incidence of infection was 14% (95% CI 10–18; p<0·0001) at a median follow-up time of 30 days for MDR-GNB (845 cases of infection in 9034 patients colonised) and 8% (5–13; p<0·0001) at 30 days for VRE (229 cases of infection in 4747 patients colonised). Infection incidence density (4·26 infections per 1000 patient-days; 95% CI 1·69–6·82) and cumulative incidence of infection (19%, 95% CI 15–25; p<0·0001; 602 cases of infection in 4547 patients colonised) were highest for carbapenem-resistant Gram-negative bacteria at 30 days. Risk of bias was rated low to moderate.
The risk of infection was substantial, with the highest risk for patients colonised with carbapenem-resistant Gram-negative bacteria and the lowest in patients with VRE. These data might help to guide prophylactic and treatment decisions and form a valuable resource for planning clinical trials on targeted prevention.
The Netherlands Organization for Health Research and Development
Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great ...a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements.
To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis.
We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014.
We included cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG).
Two review authors independently assessed quality and extracted data. We carried out meta-analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates.
We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 82% (73% to 90%) and the specificity was 81% (72% to 90%). At a cut-off value of 1.0 ODI, the sensitivity was 72% (65% to 80%) and the specificity was 88% (84% to 92%). At a cut-off value of 1.5 ODI, the sensitivity was 61% (47% to 75%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity.
If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 9% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 82%, 18% false negatives), and 17 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 81%, 19% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.
Context.
Polarised emission from non-spherical dust grains contains information about the alignment of these dust grains and traces the structure of the interstellar magnetic field.
Methods.
We ...post-processed a set of Milky-Way-like galaxies from the Auriga project, assuming a dust mix consisting of spheroidal dust grains that are partially aligned with the model magnetic field. We constrained our dust model using
Planck
353 GHz observations of the Milky Way. This model was then extrapolated to shorter wavelengths that cover the peak of interstellar dust emission and to observations of arbitrarily oriented nearby Milky-Way-like galaxies.
Results.
Assuming an intrinsic linear polarisation fraction that does not vary significantly with wavelength for wavelengths longer than 50 micron, we predict a linear polarisation fraction with a maximum of 10 − 15% and a median value of ≈7% for face-on galaxies and ≈3% for edge-on galaxies. The polarisation fraction anti-correlates with the line of sight density and with the angular dispersion function which expresses the large-scale order of the magnetic field perpendicular to the line of sight. The maximum linear polarisation fraction agrees well with the intrinsic properties of the dust model. The true magnetic field orientation can be traced along low density lines of sight when it is coherent along the line of sight. These results also hold for nearby galaxies, where a coherent magnetic field structure is recovered over a range of different broad bands.
Conclusions.
Polarised emission from non-spherical dust grains accurately traces the large-scale structure of the galactic magnetic field in Milky-Way-like galaxies, with expected maximum linear polarisation fractions of 10 − 15%. To resolve this maximum, a spatial resolution of at least 1 kpc is required.
Female hormones and thrombosis Rosendaal, F R; Helmerhorst, F M; Vandenbroucke, J P
Arteriosclerosis, thrombosis, and vascular biology,
2002-February, Letnik:
22, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Exogenous hormones are used by more than a hundred million women worldwide as oral contraceptives or for postmenopausal hormone replacement. Oral contraceptives increase the risk of venous ...thrombosis, of myocardial infarction, and of stroke. The risk is highest during the first year of use. The venous thrombotic risk of oral contraceptives is high among women with coagulation abnormalities and with so-called third-generation contraceptives (containing desogestrel or gestodene). The risk of myocardial infarction does not appear to depend on coagulation abnormalities or the type of oral contraceptive. Hormone replacement therapy increases the risk of venous thrombosis. This risk is also highest in the first year of use and among women with coagulation abnormalities. The risk becomes very high in women with a previous venous thrombosis. Randomized trials have not confirmed a beneficial effect of postmenopausal hormones on the occurrence of myocardial infarction.
Summary
Mycobacterial genomes contain two unique gene families, the so‐called PE and PPE gene families, which are highly expanded in the pathogenic members of this genus. Here we report that one of ...the PPE proteins, i.e. PPE41, is secreted by pathogenic mycobacteria, both in culture and in infected macrophages. As PPE41 lacks a signal sequence a dedicated secretion system must be involved. A single gene was identified in Mycobacterium marinum that showed strongly reduced PPE41 secretion. This gene was located in a gene cluster whose predicted proteins encode components of an ESAT‐6‐like secretion system. This cluster, designated ESX‐5, is conserved in various pathogenic mycobacteria, but not in the saprophytic species Mycobacterium smegmatis. Therefore, different regions of this cluster were introduced in M. smegmatis. Only introduction of the complete ESX‐5 locus resulted in efficient secretion of heterologously expressed PPE41. This PPE secretion system is also involved in the virulence of pathogenic mycobacteria, as the ESX‐5 mutant of M. marinum was affected in spreading to uninfected macrophages.
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