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Donor acquired visceral leishmaniasis following liver transplantation.
No full textPatients who undergo solid organ transplantation are at risk of opportunistic infection associated with immunosuppression. We report a case of confirmed donor derived visceral leishmaniasis (VL), in a patient following liver transplantation causing fever and pancytopenia. The diagnosis was confirmed by bone marrow biopsy, with confirmed positive donor serology, with no other route of transmission. To our knowledge, this is the first case report in the United Kingdom and Europe, of confirmed organ donor transmission of VL. This case report highlights an important consideration of donor derived infections, in the context of solid organ transplantation
Effects of Spironolactone and Chlorthalidone on Cardiovascular Structure and Function in Chronic Kidney Disease: A Randomized, Open-Label Trial.
No full textBACKGROUND AND OBJECTIVES
In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30-89 ml/min per 1.73 m). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg).
RESULTS
There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was -3.8 g (95% confidence interval, -8.1 to 0.5 g, =0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (-0.4 m/s, 0.5 m/s, =0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, =0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, =0.07).
CONCLUSIONS
Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD
Adhesion-related readmissions after open and laparoscopic colorectal surgery in 16 524 patients.
No full textAIM
Colorectal surgery is associated with a high risk of adhesion formation and subsequent complications. Laparoscopic colorectal surgery reduces adhesion formation by 50%; however, the effect on adhesion-related complications is still unknown. This study aims to compare differences in incidence rates of adhesion-related readmissions after laparoscopic and open colorectal surgery.
METHOD
Population data from the Scottish National Health Service were used to identify patients who underwent colorectal surgery between June 2009 and June 2011. Readmissions were registered until December 2017 and categorized as being either directly or possibly related to adhesions, or as reoperations potentially complicated by adhesions. The primary outcome measure was the difference in incidence of directly adhesion-related readmissions between the open and laparoscopic cohort.
RESULTS
Colorectal surgery was performed in 16 524 patients; 4455 (27%) underwent laparoscopic surgery. Patients undergoing laparoscopic surgery were readmitted less frequently for directly adhesion-related complications, 2.4% (95% CI 2.0%-2.8%) versus 7.5% (95% CI 7.1%-7.9%) in the open cohort. Readmissions for possibly adhesion-related complications were less frequent in the laparoscopic cohort, 16.8% (95% CI 15.6%-18.0%) versus 21.7% (95% CI 20.9%-22.5%), as well as reoperations potentially complicated by adhesions, 9.7% (95% CI 8.9%-10.5%) versus 16.9% (95% CI 16.3%-17.5%).
CONCLUSION
Overall, any adhesion-related readmissions occurred in over one in three patients after open colorectal surgery and one in four after laparoscopic colorectal surgery. Compared with open surgery, incidence rates of adhesion-related complications decrease but remain substantial after laparoscopic surgery
Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing in Kidney Transplant Recipients.
No full textThere are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages
Metabotypes of flavan-3-ol colonic metabolites after cranberry intake: elucidation and statistical approaches.
No full textPURPOSE
Extensive inter-individual variability exists in the production of flavan-3-ol metabolites. Preliminary metabolic phenotypes (metabotypes) have been defined, but there is no consensus on the existence of metabotypes associated with the catabolism of catechins and proanthocyanidins. This study aims at elucidating the presence of different metabotypes in the urinary excretion of main flavan-3-ol colonic metabolites after consumption of cranberry products and at assessing the impact of the statistical technique used for metabotyping.
METHODS
Data on urinary concentrations of phenyl-γ-valerolactones and 3-(hydroxyphenyl)propanoic acid derivatives from two human interventions has been used. Different multivariate statistics, principal component analysis (PCA), cluster analysis, and partial least square-discriminant analysis (PLS-DA), have been considered.
RESULTS
Data pre-treatment plays a major role on resulting PCA models. Cluster analysis based on k-means and a final consensus algorithm lead to quantitative-based models, while the expectation-maximization algorithm and clustering according to principal component scores yield metabotypes characterized by quali-quantitative differences in the excretion of colonic metabolites. PLS-DA, together with univariate analyses, has served to validate the urinary metabotypes in the production of flavan-3-ol metabolites and to confirm the robustness of the methodological approach.
CONCLUSIONS
This work proposes a methodological workflow for metabotype definition and highlights the importance of data pre-treatment and clustering methods on the final outcomes for a given dataset. It represents an additional step toward the understanding of the inter-individual variability in flavan-3-ol metabolism.
TRIAL REGISTRATION
The acute study was registered at clinicaltrials.gov as NCT02517775, August 7, 2015; the chronic study was registered at clinicaltrials.gov as NCT02764749, May 6, 2016
Contemporary use of antimicrobial prophylaxis for surgical patients: An observational cohort study.
No full textBACKGROUND
Antimicrobial prophylaxis is commonly used to prevent surgical site infection (SSI), despite concerns of overuse leading to antimicrobial resistance. However, it is unclear how often antimicrobials are used and whether guidelines are followed.
OBJECTIVES
To describe contemporary clinical practice for antimicrobial prophylaxis including guideline compliance, the rate of postoperative infection and associated side effects.
DESIGN
A prospective, multicentre, observational cohort study.
SETTING
Twelve United Kingdom National Health Service hospitals.
PARTICIPANTS
One thousand one hundred and sixteen patients, aged at least 18 years undergoing specific colorectal, obstetric, gynaecological, urological or orthopaedic surgical procedures.
EXPOSURE
Compliance with guidelines for antimicrobial prophylaxis.
OUTCOMES
The primary outcome was SSI within 30 days after surgery. Secondary outcomes were number of doses of antimicrobials for prophylaxis and to treat infection, incidence of antimicrobial-related side effects and mortality within 30 days after surgery. Data are presented as number with percentage (%) or median with interquartile range [IQR]. Results of logistic regression analyses are presented as odds ratio/rate ratio (OR) with 95% confidence intervals (95% CIs).
RESULTS
One thousand one hundred and two out of 1106 (99.6%) patients received antimicrobial prophylaxis, which was compliant with local guidelines in 929 out of 1102 (84.3%) cases. Two thousand one hundred and sixty-nine out of 5128 (42.3%) doses of antimicrobials were administered as prophylaxis (median 1 [1 to 2] dose) and 2959 out of 5128 (57.7%) were administered to treat an infection (median 21 [11 to 28] doses). Fifty-six patients (5.2%) developed SSI. Antimicrobial prophylaxis administered according to local guidelines was not associated with a lower incidence of SSI compared with administration outside guidelines [OR 0.90 (0.35 to 2.29); P = 0.823]. Twenty-three out of 1072 (2.2%) patients experienced a side effect of antimicrobial therapy. Seven out of 1082 (0.6%) patients died. The median hospital stay was 3 [1 to 5] days.
CONCLUSION
Antimicrobial prophylaxis was administered for almost all the surgical procedures under investigation. However, this was not always compliant with guidelines. Further research is required to determine whether the amount of prophylactic antimicrobials could be safely and effectively reduced without increasing the incidence of SSI
Systematic review of imaging tests to predict the development of rheumatoid arthritis in people with unclassified arthritis.
No full textOBJECTIVE
To estimate and compare the diagnostic accuracy of magnetic resonance imaging (MRI) and ultrasound, for the prediction of rheumatoid arthritis (RA) in unclassified arthritis (UA).
METHODS
MEDLINE, Embase and BIOSIS were searched from 1987 to May 2019. Studies evaluating any imaging test in participants with UA were eligible. Reference standards were RA classification criteria or methotrexate initiation. Two authors independently extracted data and assessed validity using QUADAS-2. Sensitivities and specificities were calculated for each imaging characteristic and joint area. Summary estimates with 95% confidence intervals (CI) were estimated where possible.
RESULTS
Nineteen studies were included; 13 evaluated MRI (n=1,143; 454 with RA) and 6 evaluated ultrasound (n=531; 205 with RA). Studies were limited by unclear recruitment procedures, inclusion of patients with RA at baseline, differential verification, lack of blinding and consensus grading. Study heterogeneity largely precluded meta-analysis, however summary sensitivity and specificity for MRI synovitis in at least one joint were 93% (95% CI 88%, 96%) and 25% (95% CI 13%, 41%) (3 studies). Specificities may be higher for other MRI characteristics but data are limited. Ultrasound results were difficult to synthesise due to different diagnostic thresholds and reference standards.
CONCLUSION
The evidence for MRI or ultrasound as single tests for predicting RA in people with UA is heterogeneous and of variable methodological quality. Larger studies using consensus grading and consistently defined RA diagnosis are needed to identify whether combinations of imaging characteristics, either alone or in combination with other clinical findings, can better predict RA in this population
Mifepristone and misoprostol versus placebo and misoprostol for resolution of miscarriage in women diagnosed with missed miscarriage: the MifeMiso RCT.
No full textTRIAL DESIGN
A randomised, parallel-group, double-blind, placebo-controlled multicentre study with health economic and nested qualitative studies to determine if mifepristone (Mifegyne, Exelgyn, Paris, France) plus misoprostol is superior to misoprostol alone for the resolution of missed miscarriage.
METHODS
Women diagnosed with missed miscarriage in the first 14 weeks of pregnancy were randomly assigned (1 : 1 ratio) to receive 200 mg of oral mifepristone or matched placebo, followed by 800 μg of misoprostol 2 days later. A web-based randomisation system allocated the women to the two groups, with minimisation for age, body mass index, parity, gestational age, amount of bleeding and randomising centre. The primary outcome was failure to pass the gestational sac within 7 days after randomisation. The prespecified key secondary outcome was requirement for surgery to resolve the miscarriage. A within-trial cost-effectiveness study and a nested qualitative study were also conducted. Women who completed the trial protocol were purposively approached to take part in an interview to explore their satisfaction with and the acceptability of medical management of missed miscarriage.
RESULTS
A total of 711 women, from 28 hospitals in the UK, were randomised to receive either mifepristone plus misoprostol (357 women) or placebo plus misoprostol (354 women). The follow-up rate for the primary outcome was 98% (696 out of 711 women). The risk of failure to pass the gestational sac within 7 days was 17% (59 out of 348 women) in the mifepristone plus misoprostol group, compared with 24% (82 out of 348 women) in the placebo plus misoprostol group (risk ratio 0.73, 95% confidence interval 0.54 to 0.98; = 0.04). Surgical intervention to resolve the miscarriage was needed in 17% (62 out of 355 women) in the mifepristone plus misoprostol group, compared with 25% (87 out of 353 women) in the placebo plus misoprostol group (risk ratio 0.70, 95% confidence interval 0.52 to 0.94; = 0.02). There was no evidence of a difference in the incidence of adverse events between the two groups. A total of 42 women, 19 in the mifepristone plus misoprostol group and 23 in the placebo plus misoprostol group, took part in an interview. Women appeared to have a preference for active management of their miscarriage. Overall, when women experienced care that supported their psychological well-being throughout the care pathway, and information was delivered in a skilled and sensitive manner such that women felt informed and in control, they were more likely to express satisfaction with medical management. The use of mifepristone and misoprostol showed an absolute effect difference of 6.6% (95% confidence interval 0.7% to 12.5%). The average cost per woman was lower in the mifepristone plus misoprostol group, with a cost saving of £182 (95% confidence interval £26 to £338). Therefore, the use of mifepristone and misoprostol for the medical management of a missed miscarriage dominated the use of misoprostol alone.
LIMITATIONS
The results from this trial are not generalisable to women diagnosed with incomplete miscarriage and the study does not allow for a comparison with expectant or surgical management of miscarriage.
FUTURE WORK
Future work should use existing data to assess and rank the relative clinical effectiveness and safety profiles for all methods of management of miscarriage.
CONCLUSIONS
Our trial showed that pre-treatment with mifepristone followed by misoprostol resulted in a higher rate of resolution of missed miscarriage than misoprostol treatment alone. Women were largely satisfied with medical management of missed miscarriage and would choose it again. The mifepristone and misoprostol intervention was shown to be cost-effective in comparison to misoprostol alone.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN17405024.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 68. See the NIHR Journals Library website for further project information
