Clostridium difficile Infection Leffler, Daniel A; Lamont, J. Thomas
The New England journal of medicine,
04/2015, Letnik:
372, Številka:
16
Journal Article
Recenzirano
This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors. New treatments ...include fecal microbiota transplantation for disease that is resistant to vancomycin.
Clostridium difficile
is an anaerobic gram-positive, spore-forming, toxin-producing bacillus that is transmitted among humans through the fecal–oral route. The relationship between the bacillus and humans was once thought to be commensal,
1
but
C. difficile
has emerged as a major enteric pathogen with worldwide distribution. In the United States,
C. difficile
is the most frequently reported nosocomial pathogen. A surveillance study in 2011 identified 453,000 cases of
C. difficile
infection and 29,000 deaths associated with
C. difficile
infection; approximately a quarter of those infections were community-acquired.
2
Nosocomial
C. difficile
infection more than quadruples the cost of hospitalizations,
3
increasing annual expenditures by . . .
Clostridium difficile
is the leading cause of nosocomial infectious diarrhea. New treatment strategies are needed. In this letter, preliminary data on fecal therapy as primary treatment are assessed.
Background
Dental plaque associated gingivitis is a reversible inflammatory condition caused by accumulation and persistence of microbial biofilms (dental plaque) on the teeth. It is characterised by ...redness and swelling of the gingivae (gums) and a tendency for the gingivae to bleed easily. In susceptible individuals, gingivitis may lead to periodontitis and loss of the soft tissue and bony support for the tooth. It is thought that chlorhexidine mouthrinse may reduce the build‐up of plaque thereby reducing gingivitis.
Objectives
To assess the effectiveness of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for the control of gingivitis and plaque compared to mechanical oral hygiene procedures alone or mechanical oral hygiene procedures plus placebo/control mouthrinse. Mechanical oral hygiene procedures were toothbrushing with/without the use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment.
To determine whether the effect of chlorhexidine mouthrinse is influenced by chlorhexidine concentration, or frequency of rinsing (once/day versus twice/day).
To report and describe any adverse effects associated with chlorhexidine mouthrinse use from included trials.
Search methods
Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 28 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 28 September 2016); MEDLINE Ovid (1946 to 28 September 2016); Embase Ovid (1980 to 28 September 2016); and CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 28 September 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.
Selection criteria
We included randomised controlled trials assessing the effects of chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for at least 4 weeks on gingivitis in children and adults. Mechanical oral hygiene procedures were toothbrushing with/without use of dental floss or interdental cleaning aids and could include professional tooth cleaning/periodontal treatment. We included trials where participants had gingivitis or periodontitis, where participants were healthy and where some or all participants had medical conditions or special care needs.
Data collection and analysis
Two review authors independently screened the search results extracted data and assessed the risk of bias of the included studies. We attempted to contact study authors for missing data or clarification where feasible. For continuous outcomes, we used means and standard deviations to obtain the mean difference (MD) and 95% confidence interval (CI). We combined MDs where studies used the same scale and standardised mean differences (SMDs) where studies used different scales. For dichotomous outcomes, we reported risk ratios (RR) and 95% CIs. Due to anticipated heterogeneity we used random‐effects models for all meta‐analyses.
Main results
We included 51 studies that analysed a total of 5345 participants. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however, this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect.
Gingivitis
After 4 to 6 weeks of use, chlorhexidine mouthrinse reduced gingivitis (Gingival Index (GI) 0 to 3 scale) by 0.21 (95% CI 0.11 to 0.31) compared to placebo, control or no mouthrinse (10 trials, 805 participants with mild gingival inflammation (mean score 1 on the GI scale) analysed, high‐quality evidence). A similar effect size was found for reducing gingivitis at 6 months. There were insufficient data to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 (moderate or severe levels of gingival inflammation).
Plaque
Plaque was measured by different indices and the SMD at 4 to 6 weeks was 1.45 (95% CI 1.00 to 1.90) standard deviations lower in the chlorhexidine group (12 trials, 950 participants analysed, high‐quality evidence), indicating a large reduction in plaque. A similar large reduction was found for chlorhexidine mouthrinse use at 6 months.
Extrinsic tooth staining
There was a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 4 to 6 weeks. The SMD was 1.07 (95% CI 0.80 to 1.34) standard deviations higher (eight trials, 415 participants analysed, moderate‐quality evidence) in the chlorhexidine mouthrinse group. There was also a large increase in extrinsic tooth staining in participants using chlorhexidine mouthrinse at 7 to 12 weeks and 6 months.
Calculus
Results for the effect of chlorhexidine mouthrinse on calculus formation were inconclusive.
Effect of concentration and frequency of rinsing
There were insufficient data to determine whether there was a difference in effect for either chlorhexidine concentration or frequency of rinsing.
Other adverse effects
The adverse effects most commonly reported in the included studies were taste disturbance/alteration (reported in 11 studies), effects on the oral mucosa including soreness, irritation, mild desquamation and mucosal ulceration/erosions (reported in 13 studies) and a general burning sensation or a burning tongue or both (reported in nine studies).
Authors' conclusions
There is high‐quality evidence from studies that reported the Löe and Silness Gingival Index of a reduction in gingivitis in individuals with mild gingival inflammation on average (mean score of 1 on the 0 to 3 GI scale) that was not considered to be clinically relevant. There is high‐quality evidence of a large reduction in dental plaque with chlorhexidine mouthrinse used as an adjunct to mechanical oral hygiene procedures for 4 to 6 weeks and 6 months. There is no evidence that one concentration of chlorhexidine rinse is more effective than another. There is insufficient evidence to determine the reduction in gingivitis associated with chlorhexidine mouthrinse use in individuals with mean GI scores of 1.1 to 3 indicating moderate or severe levels of gingival inflammation. Rinsing with chlorhexidine mouthrinse for 4 weeks or longer causes extrinsic tooth staining. In addition, other adverse effects such as calculus build up, transient taste disturbance and effects on the oral mucosa were reported in the included studies.
In clinical practices for adults and children, probiotics — live bacteria that are intended to have a beneficial effect in the host — are frequently recommended to treat a wide variety of diarrheal ...diseases. The results of thousands of studies of probiotics have been published, and most of them have shown that probiotics are effective in treating or preventing various forms of acute and chronic diarrhea. Acute infectious gastroenteritis in children remains a major public health issue, particularly in low-income countries, where this condition accounts for substantial neonatal mortality. Follow-up from one study
1
that enrolled more than 20,000 infants and . . .
Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced bacterial toxins and diminished ...host immune response contribute to symptomatic disease. C. difficile has been a well-established pathogen in North America and Europe for decades, but is just emerging in Asia. This article reviews the epidemiology, microbiology, pathophysiology, and clinical management of C. difficile. Prompt recognition of C. difficile is necessary to implement appropriate infection control practices.
There is no agreement which outcomes should be measured when investigating interventions for periodontal diseases. It is difficult to compare or combine studies with different outcomes; resulting in ...research wastage and uncertainty for patients and healthcare professionals.
Develop a core outcome set (COS) relevant to key stakeholders for use in effectiveness trials investigating prevention and management of periodontal diseases.
Mixed method study involving literature review; online Delphi Study; and face-to-face consensus meeting.
Key stakeholders: patients, dentists, hygienist/therapists, periodontists, researchers.
The literature review identified 37 unique outcomes. Delphi round 1: 20 patients and 51 dental professional and researchers prioritised 25 and suggested an additional 11 outcomes. Delphi round 2: from the resulting 36 outcomes, 13 patients and 39 dental professionals and researchers prioritised 22 outcomes. A face-to-face consensus meeting was hosted in Dundee, Scotland by an independent chair. Eight patients and six dental professional and researchers participated. The final COS contains: Probing depths, Quality of life, Quantified levels of gingivitis, Quantified levels of plaque, Tooth loss.
Implementation of this COS will ensure the results of future effectiveness trials for periodontal diseases are more relevant to patients and dental professionals, reducing research wastage. This could reduce uncertainty for patients and dental professionals by ensuring the evidence used to inform their choices is meaningful to them. It could also strengthen the quality and certainty of the evidence about the relative effectiveness of interventions.
COMET Database: http://www.comet-initiative.org/studies/details/265?result=true.
Metamorphic core complexes (MCCs) are interpreted as domal structures exposing ductile deformed high-grade metamorphic rocks in the core underlying a ductile-to-brittle high-strain detachment that ...experienced tens of kilometres of normal sense displacement in response to lithospheric extension. Extension is supposedly the driving force that has governed exhumation. However, numerous core complexes, notably Himalayan, Karakoram and Pamir domes, occur in wholly compressional environments and are not related to lithospheric extension. We suggest that many MCCs previously thought to form during extension are instead related to compressional tectonics. Pressures of kyanite-and sillimanite-grade rocks in the cores of many of these domes are c. 10-14 kbar, approximating to exhumation from depths of c. 35-45 km, too great to be accounted for solely by isostatic uplift. The evolution of high-grade metamorphic rocks is driven by crustal thickening, shortening, regional Barrovian metamorphism, isoclinal folding and ductile shear in a compressional tectonic setting prior to regional extension. Extensional fabrics commonly associated with all these core complexes result from reverse flow along an orogenic channel (channel flow) following peak metamorphism beneath a passive roof stretching fault. In Naxos, low-angle normal faults associated with regional Aegean extension cut earlier formed compressional folds and metamorphic fabrics related to crustal shortening and thickening. The fact that low-angle normal faults exist in both extensional and compressional tectonic settings, and can actively slip at low angles (<30°), suggests that a re-evaluation of the Andersonian mechanical theory that requires normal faults to form and slip only at high angles (c. 60°) is needed.
The management of dental caries has traditionally involved removal of all soft demineralised dentine before a filling is placed. However, the benefits of complete caries removal have been questioned ...because of concerns about the possible adverse effects of removing all soft dentine from the tooth. Three groups of studies have also challenged the doctrine of complete caries removal by sealing caries into teeth using three different techniques. The first technique removes caries in stages over two visits some months apart, allowing the dental pulp time to lay down reparative dentine (the stepwise excavation technique). The second removes part of the dentinal caries and seals the residual caries into the tooth permanently (partial caries removal) and the third technique removes no dentinal caries prior to sealing or restoring (no dentinal caries removal). This is an update of a Cochrane review first published in 2006.
To assess the effects of stepwise, partial or no dentinal caries removal compared with complete caries removal for the management of dentinal caries in previously unrestored primary and permanent teeth.
The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 12 December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 11), MEDLINE via OVID (1946 to 12 December 2012) and EMBASE via OVID (1980 to 12 December 2012). There were no restrictions regarding language or date of publication.
Parallel group and split-mouth randomised and quasi-randomised controlled trials comparing stepwise, partial or no dentinal caries removal with complete caries removal, in unrestored primary and permanent teeth were included.
Three review authors extracted data independently and in triplicate and assessed risk of bias. Trial authors were contacted where possible for information. We used standard methodological procedures exacted by The Cochrane Collaboration.
In this updated review, four new trials were included bringing the total to eight trials with 934 participants and 1372 teeth. There were three comparisons: stepwise caries removal compared to complete one stage caries removal (four trials); partial caries removal compared to complete caries removal (three trials) and no dentinal caries removal compared to complete caries removal (two trials). (One three-arm trial compared complete caries removal to both stepwise and partial caries removal.) Four studies investigated primary teeth, three permanent teeth and one included both. All of the trials were assessed at high risk of bias, although the new trials showed evidence of attempts to minimise bias.Stepwise caries removal resulted in a 56% reduction in incidence of pulp exposure (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.33 to 0.60, P < 0.00001, I(2) = 0%) compared to complete caries removal based on moderate quality evidence, with no heterogeneity. In these four studies, the mean incidence of pulp exposure was 34.7% in the complete caries removal group and 15.4% in the stepwise groups. There was also moderate quality evidence of no difference in the outcome of signs and symptoms of pulp disease (RR 0.78, 95% CI 0.39 to 1.58, P = 0.50, I(2) = 0%).Partial caries removal reduced incidence of pulp exposure by 77% compared to complete caries removal (RR 0.23, 95% CI 0.08 to 0.69, P = 0.009, I(2) = 0%), also based on moderate quality evidence with no evidence of heterogeneity. In these two studies the mean incidence of pulp exposure was 21.9% in the complete caries removal groups and 5% in the partial caries removal groups. There was insufficient evidence to determine whether or not there was a difference in signs and symptoms of pulp disease (RR 0.27, 95% CI 0.05 to 1.60, P = 0.15, I(2) = 0%, low quality evidence), or restoration failure (one study showing no difference and another study showing no failures in either group, very low quality evidence).No dentinal caries removal was compared to complete caries removal in two very different studies. There was some moderate evidence of no difference between these techniques for the outcome of signs and symptoms of pulp disease and reduced risk of restoration failure favouring no dentinal caries removal, from one study, and no instances of pulp disease or restoration failure in either group from a second quasi-randomised study. Meta-analysis of these two studies was not performed due to substantial clinical differences between the studies.
Stepwise and partial excavation reduced the incidence of pulp exposure in symptomless, vital, carious primary as well as permanent teeth. Therefore these techniques show clinical advantage over complete caries removal in the management of dentinal caries. There was no evidence of a difference in signs or symptoms of pulpal disease between stepwise excavation, and complete caries removal, and insufficient evidence to determine whether or not there was a difference in signs and symptoms of pulp disease between partial caries removal and complete caries removal. When partial caries removal was carried out there was also insufficient evidence to determine whether or not there is a difference in risk of restoration failure. The no dentinal caries removal studies investigating permanent teeth had a similar result with no difference in restoration failure. The other no dentinal caries removal study, which investigated primary teeth, showed a statistically significant difference in restoration failure favouring the intervention.Due to the short term follow-up in most of the included studies and the high risk of bias, further high quality, long term clinical trials are still required to assess the most effective intervention. However, it should be noted that in studies of this nature, complete elimination of risk of bias may not necessarily be possible. Future research should also investigate patient centred outcomes.
The Aegean Sea area is thought to be an actively extending back-arc region, north of the present day Hellenic volcanic arc and north-dipping subduction zone in the Eastern Mediterranean. The area ...shows extensive normal faulting, ductile ‘extensional’ shear zones and extensional S-C fabrics throughout the islands that have previously been related to regional Aegean extension associated with slab rollback on the Hellenic Subduction Zone. In this paper, we question this interpretation, and suggest the Cenozoic geodynamic evolution of the Aegean region is associated with a Late Cretaceous–Eocene NE-dipping subduction zone that was responsible for continent-continent collision between Eurasia and Adria-Apulia/Cyclades. Exhumation of eclogite and blueschist facies rocks in the Cyclades and kyanite-sillimanite grade gneisses in the Naxos core complex have pressures that are far greater than could be accounted for purely by lithospheric extension and isostatic uplift. We identify four stages of crustal shortening that affected the region prior to regional lithospheric extension, herein called the Aegean Orogeny. This orogeny followed a classic Wilson cycle from early ophiolite obduction (ca. 74 Ma) onto a previously passive continental margin, to attempted crustal subduction with HP eclogite and blueschist facies metamorphism (ca. 54–45 Ma), through crustal thickening and regional kyanite – sillimanite grade Barrovian-type metamorphism (ca. 22–14 Ma), to orogenic collapse (<14 Ma). At least three periods of ‘extensional’ fabrics relate to: (1) Exhumation of blueschists and eclogite facies rocks showing tight-isoclinal folds and top-NE, base-SW fabrics, recording return flow along a subduction channel in a compressional tectonic setting (ca. 50–35 Ma). (2) Extensional fabrics within the core complexes formed by exhumation of kyanite- and sillimanite gneisses showing thrust-related fabrics at the base and ‘extensional’ fabrics along the top (ca. 18.5–14 Ma). (3) Regional ductile-brittle ‘extensional’ fabrics and low-angle normal faulting related to the North Cycladic Detachment (NCD) and the South(West) Cycladic Detachment (WCD) during regional extension along the flanks of a major NW–SE anticlinal fold along the middle of the Cyclades. Major low-angle normal faults and ductile shear zones show symmetry about the area, with the NE chain of islands (Andros, Tinos, Mykonos, Ikaria) exposing the NE-dipping NCD with consistent top-NE ductile fabrics along 200 km of strike. In contrast, from the Greek mainland (Attica) along the SE chain of islands (Kea, Kythnos, Serifos) a SW-dipping low-angle normal fault and ductile shear zone, the WCD is inferred for at least 100 km along strike. Islands in the middle of the Cyclades show deeper structural levels including kyanite- and sillimanite-grade metamorphic core complexes (Naxos, Paros) as well as Variscan basement rocks (Naxos, Ios). The overall structure is an ~100 km wavelength NW–SE trending dome with low-angle extensional faults along each flank, dipping away from the anticline axis to the NE and SW. Many individual islands show post-extensional large-scale folding of the low-angle normal faults around the domes (Naxos, Paros, Ios, Sifnos) indicating a post-Miocene late phase of E–W shortening.
•Cyclades Islands show an orogenic history lasting >70 m.y. covering whole Wilson cycle.•Cretaceous ophiolite obduction was followed by Eocene subduction of the continental margin to eclogite-blueschist facies.•Eocene continental collision resulted in regional kyanite-sillimanite grade metamorphism in a compressional core complex.•Late Miocene-Pliocene low-angle extension ductile shear zones were subsequently folded along NW-SE aligned dome axis.
Clostridium difficile infection is an increasing burden to the health care system, totaling more than $1 billion/year in the United States. Treatment of patients with C difficile infection with ...metronidazole or vancomycin reduces morbidity and mortality, although the number of patients that do not respond to metronidazole is increasing. Despite initial response rates of greater than 90%, 15%–30% of patients have a relapse in symptoms after successful initial therapy, usually in the first few weeks after treatment is discontinued. Failure to develop specific antibody response has recently been identified as a critical factor in recurrence. The review discusses the different management strategies for initial and recurrent symptomatic C difficile infections.
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