Clostridium difficile
infection can be life-threatening and difficult to treat, with frequent relapses. In this study in patients with recurrent
C. difficile
–associated diarrhea, infusion of healthy ...donor feces significantly decreased relapses, as compared with vancomycin therapy.
Antibiotic treatment for an initial
Clostridium difficile
infection typically does not induce a durable response in approximately 15 to 26% of patients.
1
–
3
An effective treatment against recurrent
C. difficile
infection is not available. Generally, repeated and extended courses of vancomycin are prescribed.
4
The estimated efficacy of antibiotic therapy for a first recurrence is 60%, a proportion that further declines in patients with multiple recurrences.
2
,
5
–
7
Mechanisms that have been proposed for recurrence include persistence of spores of
C. difficile,
diminished antibody response to clostridium toxins, and persistent disturbance with a reduced diversity of intestinal microbiota.
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–
12
Infusion of . . .
In a randomized, delayed-start trial of levodopa in Parkinson’s disease, with one group receiving the drug for 80 weeks and the other starting at 40 weeks, the difference between the groups in the ...progression of symptoms was not significant.
This study compared surgical outcomes before and after implementation of a comprehensive checklist, including marking of the operative side and use of postoperative instructions. Complications ...decreased from 27 to 17 per 100 patients, and mortality decreased from 1.5 to 0.7%.
Hospitals are not the safe places we would like them to be. A systematic review has shown that 1 in every 150 patients admitted to a hospital dies as a consequence of an adverse event and that almost two thirds of in-hospital events are associated with surgical care.
1
In recognition of the disproportionate number of such events that are associated with surgical care, several interventions have been proposed to increase patient safety, including relegating surgical procedures to high-volume centers, establishing training programs for laparoscopic surgery, and improving the quality of teamwork in the operating room.
2
–
4
In addition, a number . . .
To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD).
Multicentre, randomized, controlled, double-masked clinical trial in ...327 patients. The non-inferiority margin was 4 letters.
Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV) secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA) score between 20 and 78 letters on an EDTRS like chart in the study eye.
Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed.
Primary outcome was the change in BCVA in the study eye from baseline to 12 months.
The mean gain in BCVA was 5.1 (±14.1) letters in the bevacizumab group (n = 161) and 6.4 (±12.2) letters in the ranibizumab group (n = 166) (p = 0.37). The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038). No significant differences in absolute CRT and CRT change (p = 0.13) or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively) were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal) differed significantly (p = 0.020), with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively).
Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both gainers and losers and more frequently observed retinal fluid on SD-OCT at 12 months when compared to the ranibizumab group.
Trialregister.nl NTR1704.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Published work suggests a survival benefit for patients with trauma who undergo total-body CT scanning during the initial trauma assessment; however, level 1 evidence is absent. We ...aimed to assess the effect of total-body CT scanning compared with the standard work-up on in-hospital mortality in patients with trauma. Methods We undertook an international, multicentre, randomised controlled trial at four hospitals in the Netherlands and one in Switzerland. Patients aged 18 years or older with trauma with compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury were randomly assigned (1:1) by ALEA randomisation to immediate total-body CT scanning or to a standard work-up with conventional imaging supplemented with selective CT scanning. Neither doctors nor patients were masked to treatment allocation. The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury. The χ2 test was used to assess differences in mortality. This trial is registered with ClinicalTrials.gov , number NCT01523626. Findings Between April 22, 2011, and Jan 1, 2014, 5475 patients were assessed for eligibility, 1403 of whom were randomly assigned: 702 to immediate total-body CT scanning and 701 to the standard work-up. 541 patients in the immediate total-body CT scanning group and 542 in the standard work-up group were included in the primary analysis. In-hospital mortality did not differ between groups (total-body CT 86 16% of 541 vs standard work-up 85 16% of 542; p=0·92). In-hospital mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 22% of 362 vs standard work-up 82 25% of 331; p=0·46) and traumatic brain injury (68 38% of 178 vs 66 44% of 151; p=0·31). Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation. All five patients died. Interpretation Diagnosing patients with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT. Funding ZonMw, the Netherlands Organisation for Health Research and Development.
Background
The Stent‐In 2 trial randomized patients with malignant colonic obstruction to emergency surgery or stent placement as a bridge to elective surgery. The aim of this study was to compare ...the oncological outcomes.
Methods
Disease recurrence, and disease‐free, disease‐specific and overall survival were evaluated, including a subgroup analysis of patients with a stent‐ or guidewire‐related perforation.
Results
Of 98 patients included in the original Stent‐In 2 trial, patients with benign (16) or incurable (23) disease were excluded from this study, along with a patient who had withdrawn from the trial. Of the remaining 58 patients, 32 were randomized to emergency surgery (31 resection, 1 stoma only) and 26 to stenting. Unsuccessful stenting required emergency surgery in six patients owing to wire or stent perforation. Locoregional or distant disease recurrence developed in nine of 32 patients in the emergency surgery group and 13 of 26 in the stent group. Disease‐free survival was worse in the subgroup with stent‐ or guidewire‐related perforation. Five of six patients in this subgroup developed a recurrence, compared with nine of 32 in the emergency surgery group and eight of 20 who had unperforated stenting.
Conclusion
Stent placement for malignant colonic obstruction was associated with a risk of recurrence in this trial, but the numbers are small. There is not enough evidence to refute the approach strongly. Registration number: ISRCTN46462267 (
http://www.controlled‐trials.com).
A cautionary note
In a follow-up of a trial comparing endovascular thrombectomy with conventional therapy for acute ischemic stroke, the beneficial effect on functional recovery that was observed at 90 days was ...maintained at 2 years. Quality of life was better at 2 years with endovascular treatment.
We reported previously the 90-day outcomes of a trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands MR CLEAN) in which standard treatment was compared with endovascular treatment, administered within 6 hours after the onset of acute ischemic stroke caused by an intracranial arterial occlusion of the anterior circulation.
1
Most patients in the intervention group were treated by mechanical thrombectomy with the use of retrievable stents. The trial showed that functional recovery at 90 days was better with the intervention than with standard treatment. Subsequently, the beneficial effect of mechanical thrombectomy on 90-day outcomes . . .
Objective
Current available evidence on long-term effectiveness of enzyme replacement therapy (ERT) for Fabry disease is limited. More insight is needed whether ERT effectiveness differs in patients ...with and without baseline end-organ damage.
Design
Through a systematic review, untreated and ERT treated males and females with Fabry disease were compared for main clinical outcomes: renal function, left ventricular mass (LVmass), cerebral white matter lesions (WMLs) and end-organ complications. Through a meta-analysis ERT effectiveness was estimated in different disease stages.
Data extraction
Two reviewers assessed quality of the included studies according to guidelines for prognosis research. Data were synthesized using a random effects meta-analysis.
Results
Thirty-one studies were systematically reviewed while six studies were included in the meta-analysis. In patients with a GFR > 60 ml/min/1.73 m
2
, decline of renal function was similar for treated and untreated patients. Only ERT treated males with a GFR < 60 ml/min/1.73 m
2
had a slower rate of decline in renal function, possibly attributable to anti-proteinuric therapy. Regardless of left ventricular hypertrophy (LVH) at baseline, LVmass remained stable or increased in males despite ERT, however at a slower rate compared to untreated male patients. In ERT treated females with LVH LVmass decreased, and remained stable in females without LVH. WMLs can not be prevented by ERT. Stroke, cardiac and end-stage renal complications develop, though the incidence of new complications seems to be reduced during ERT.
Conclusion
ERT is effective in reducing LVH, but has a limited effect on renal function. Improved treatment options are needed for Fabry disease.
Over 80% of women with X-linked adrenoleukodystrophy (ALD) develop spinal cord disease in adulthood for which treatment is supportive only. For future clinical trials quantitative data on disease ...progression rates are essential. Moreover, diagnosis can be challenging in ALD women, as the most important diagnostic biomarker is normal in 15-20%. Better biomarkers are needed. The purpose of this single centre cross-sectional follow-up study in women with ALD was to assess whether Expanded Disability Status Scale (EDSS), AMC Linear Disability Scale (ALDS) and Short Form (36) Health Survey (SF-36) can detect disease progression and to model the effect of age and duration of symptoms on the rate of progression. Moreover, we performed a pilot study to assess if a semi-targeted lipidomics approach can identify possible new diagnostic biomarkers.
In this study 46 women (baseline clinical data published by our group previously) were invited for a follow-up visit. Newly identified women at our center were also recruited. We analysed 65 baseline and 34 follow-up assessments. Median time between baseline and follow-up was 7.8 years (range 6.4-8.7). Mean age at baseline was 49.2 ± 14.2 years, at follow-up 55.4 ± 10.1. EDSS increased significantly (+ 0.08 points/year), but the other outcome measures did not. Increasing age and duration of symptoms were associated with more disability. For the pilot study we analysed plasma of 20 ALD women and 10 controls with ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry, which identified 100 potential biomarker ratios with strong differentiating properties and non-overlapping data distributions between ALD women and controls.
Progression of spinal cord disease can be detected with EDSS, but not with ALDS or SF-36 after a follow-up period of almost 8 years. Moreover, age and the duration of symptoms seem positively associated with the rate of progression. Although a significant progression was measurable, it was below the rate generally conceived as clinically relevant. Therefore, EDSS, ALDS and SF-36 are not suitable as primary outcome measures in clinical trials for spinal cord disease in ALD women. In addition, a semi-targeted lipidomics approach can identify possible new diagnostic biomarkers for women with ALD.
Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which ...screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI.
Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion.
Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size.
EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.
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