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Clinical significance of 2-alkyl-4-quinolone quorum-sensing signal molecules for long-term outcomes in adults with cystic fibrosis.
No full textis an important respiratory pathogen in cystic fibrosis (CF), which is associated with an accelerated decline in lung function, frequent pulmonary exacerbations and increased mortality. produces intercellular signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence-factor production and biofilm formation in the CF airways. Studies have shown that AQs are detectable in the sputum and plasma of adults with CF and chronic pulmonary . We tested the hypothesis that the presence of six AQs in plasma or sputum obtained from adults with CF was associated with long-term adverse clinical outcomes. We analysed clinical data over an 8 year follow period for 90 people with CF who had previously provided samples for AQ analysis at clinical stability. The primary outcome was all cause mortality or lung transplantation. Secondary outcomes were the rate of lung-function decline and the number of intravenous (IV) antibiotic days for pulmonary exacerbations. There was no statistical association between the presence of any of the six measured AQs and the primary outcomes or the secondary outcome of decline in lung function. One of the six AQs was associated with IV antibiotic usage. The presence of 2-nonyl-3-hydroxy-4(1 h)-quinolone (C9-PQS) in sputum was associated with an increase in the number of IV antibiotic days in the follow-up period (Mann-Whitney; =0.011). Further investigation to confirm the hypothesis that C9-PQS may be associated with increased antibiotic usage for pulmonary exacerbations is warranted as AQ-dependent signalling is a potential future target for anti-virulence therapies
Treatments for preventing recurrence of infection with Pseudomonas aeruginosa in people with cystic fibrosis.
No full textBACKGROUND
Chronic infection with Pseudomonas aeruginosa (PA) in cystic fibrosis (CF) is a source of much morbidity and mortality. Eradication of early PA infection is possible, but can recur in many individuals. We sought to examine strategies to delay the time to PA recurrence in people with CF.
OBJECTIVES
To establish whether secondary prevention strategies, using antibiotics or other therapies, increase the chances of people with CF remaining free from PA infection following successful eradication therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 21 August 2019.
SELECTION CRITERIA
Randomised controlled trials (and quasi-randomised trials where the risk of bias was low) comparing any treatment modality aimed at preventing recurrence of PA infection with placebo, standard therapy or any other treatment modality in people with CF who have undergone successful eradication of PA.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias. Quality of the evidence was assessed using GRADE. Conflicts were resolved by discussion and the opinion of a third review author was sought where necessary. Only a subset of participants in the included trial were eligible, therefore individual participant data were requested and obtained from the trial investigators.
MAIN RESULTS
We included one trial (n = 306) in the review; however, only 253 participants had undergone successful eradication of PA, so fulfilling the inclusion criteria for our review. Information presented relates only to the included subset of participants. The trial recruited children aged one to 12 years (mean (standard deviation (SD)) age of 5.8 (3.5) years), 129 participants (51.0%) were female and the median follow-up was 494 days. We compared cycled therapy with tobramycin inhalation solution (TIS), in which participants underwent 28 days of TIS every three months, with culture-based therapy, in which participants were only prescribed medication when a quarterly sputum sample was positive for PA. Reasons for downgrading the quality of the evidence included applicability (only included children), incomplete outcome data and a small number of participants. The time to next isolation of PA was probably shorter with cycled TIS therapy than with culture-based therapy, hazard ratio (HR) 2.04 days (95% confidence interval (CI) 1.28 to 3.26) (moderate-quality evidence). This is in contrast to the main publication of the only included trial, which examined rate of PA positivity rather than time to PA infection and included participants not eligible for inclusion in this review. At the end of the trial, there was no difference between the cycled and culture-based groups in the change from baseline in forced expiratory volume in one second (FEV) L, mean difference (MD) 0.0 L (95% CI -0.09 to 0.09) or in FEV % predicted, MD 0.70% (95% CI -4.33 to 5.73) (both very low-quality evidence). There was no difference in the change from baseline for FVC between the groups. There was also no difference in the frequency of pulmonary exacerbations between groups, MD -0.18 (95% CI -0.51 to 0.14) (moderate-quality evidence). Similarly, there was no difference between groups in the risk of participants developing novel resistant bacteria, RR 1.00 (95% CI 0.67 to 1.5) (moderate-quality evidence). There were more severe adverse events in the cycled group, but the type of treatment probably makes little or no difference to the results, RR 0.65 (95% CI 0.39 to 1.11) (moderate-quality evidence). There was no difference between groups in the change in weight or height from baseline or in rates of adherence to tobramycin or all trial medicines. The included trial did not assess changes in quality of life, the time to chronic infection with PA or the cost-effectiveness of treatment.
AUTHORS' CONCLUSIONS
Cycled TIS therapy may be beneficial in prolonging the time to recurrence of PA after successful eradication, but further trials are required, specifically addressing this question and in both adults and children
Electronic patient reported outcomes to support care of patients with traumatic brain injury: PRiORiTy study qualitative protocol.
No full textINTRODUCTION
Traumatic brain injury (TBI) represents a major health and socioeconomic problem internationally. The expansive nature of injuries results in a heterogeneous population. The degree and type of long-term impacts following TBI and improvement following injury are highly variable. The use of electronic Patient Reported Outcomes Measures (ePROMs) could help identify residual impacts of TBI and support patient management and care. The Patient Reported Outcomes Research in Trauma study is a qualitative study exploring the long-term symptoms and impacts that are experienced by those with TBI and the potential utility of an ePROM platform to collect real-time information on patient symptoms and quality of life to inform treatment and identify support needs.
METHODS AND ANALYSIS
Semi-structured telephone and face-to-face interviews will be conducted with approximately 30-40 individuals recruited from five groups: (1) people with TBI; (2) carers and relatives of individuals with TBI; (3) TBI healthcare professionals; (4) researchers and (5) third sector staff members and volunteers working with those with TBI. Data will be analysed using directed thematic analysis employing an iterative coding frame that will be modified as analysis progresses. Intercoder triangulation will be employed to enhance credibility.
ETHICS AND DISSEMINATION
This study was approved by the West Midlands-Black Country Research Ethics Committee (Ref: 18/WM/0033). Findings will be disseminated via conference presentations, peer-reviewed journals, social media (@CPROR_UoB; http://www.birmingham.ac.uk/cpror) and the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre
Utility of HbA assessment in people with diabetes awaiting liver transplantation.
No full textAIMS
To investigate the relationship between HbA and glucose in people with co-existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease.
METHODS
HbA and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non-alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non-cirrhotic portal hypertension and α-1-antitrypsin-related disease.
RESULTS
The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49-63) years compared to 60 (50-71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro-Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA was 41 (32-56) mmol/mol [5.9 (5.1-7.3)%] vs 61 (52-70) mmol/mol [7.7 (6.9-8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0-11.2) mmol/l vs 7.3 (5.2-11.5) mmol/l (P=0.17). HbA was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α-1-antitrypsin disorder. Those with cirrhosis and depressed HbA had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA (r=-0.28 and r=-0.26, respectively) in the diabetes group with cirrhosis.
CONCLUSION
HbA is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation
Transcatheter versus surgical aortic valve replacement: what does the latest evidence tell us?
No full textReasons for Underreporting of Uremic Pruritus in People With Chronic Kidney Disease: A Qualitative Study.
No full textCONTEXT
Uremic pruritus, or itch, is common in people with chronic kidney disease (CKD) and has a negative impact on their lives and well-being. However, for reasons currently unknown, itch often remains unreported and therefore untreated.
OBJECTIVES
To explore reasons for underreporting of itch to provide pointers for improving itch reporting and management in people with CKD.
METHODS
We interviewed adult patients with CKD who self-reported experiencing itching in the last three years (n = 25), nephrologists (n = 10), and nurses (n = 12) from three kidney services in the U.K. Topic guides were informed by previous studies and a theoretical model of self-regulation. We conducted a thematic analysis of verbatim transcripts using framework analysis.
RESULTS
We identified the following three main themes reflecting factors that may influence whether itch is reported: knowledge on causes and treatment of itch (lack of awareness of the relationship between itch and CKD, and lack of knowledge of treatment options); attitudes toward importance of itch as a health issue (patients' and clinicians' attitudes); and prompts for itch assessment during consultations (routine practice, itch as a marker, and itch severity).
CONCLUSION
Underreporting of itch is related to patients being unaware of its causes, accepting it as something to live with, prioritizing other health issues, and the length and timing of consultations. Health care professionals' assessment and management of itch vary widely and are not necessarily evidence-based. Better patient information, development of clinical practice guidelines, and incorporation of routine symptom assessments into care may improve itch reporting and management in people with CKD
Derivation and internal validation of the screening to enhance prehospital identification of sepsis (SEPSIS) score in adults on arrival at the emergency department.
No full textBACKGROUND
Prehospital recognition of sepsis may inform case management by ambulance clinicians, as well as inform transport decisions. The objective of this study was to develop a prehospital sepsis screening tool for use by ambulance clinicians.
METHODS
We derived and validated a sepsis screening tool, utilising univariable logistic regression models to identify predictors for inclusion, and multivariable logistic regression to generate the SEPSIS score. We utilised a retrospective cohort of adult patients transported by ambulance (n = 38483) to hospital between 01 July 2013 and 30 June 2014. Records were linked using LinkPlus® software. Successful linkage was achieved in 33289 cases (86%). Eligible patients included adult, non-trauma, non-mental health, non-cardiac arrest cases. Of 33289 linked cases, 22945 cases were eligible. Eligible cases were divided into derivation (n = 16063, 70%) and validation (n = 6882, 30%) cohorts. The primary outcome measure was high risk of severe illness or death from sepsis, as defined by the National Institute for Health and Care Excellence Sepsis guideline.
RESULTS
'High risk of severe illness or death from sepsis' was present in 3.7% of derivation (n = 593) and validation (n = 254) cohorts. The SEPSIS score comprises the following variables: age, respiratory rate, peripheral oxygen saturations, heart rate, systolic blood pressure, temperature and level of consciousness (p < 0.001 for all variables). Area under the curve was 0.87 (95%CI 0.85-0.88) for the derivation cohort, and 0.86 (95%CI 0.84-0.88) for the validation cohort. In an undifferentiated adult medical population, for a SEPSIS score ≥ 5, sensitivity was 0.37 (0.31-0.44), specificity was 0.96 (0.96-0.97), positive predictive value was 0.27 (0.23-0.32), negative predictive value was 0.97 (0.96-0.97), positive likelihood value was 13.5 (9.7-18.73) and the negative likelihood value was 0.83 (0.78-0.88).
CONCLUSION
This is the first screening tool developed to identify NICE high risk of severe illness or death from sepsis. The SEPSIS score is significantly associated with high risk of severe illness or death from sepsis on arrival at the Emergency Department. It may assist ambulance clinicians to identify those patients with sepsis in need of antibiotic therapy. However, it requires external validation, in clinical practice by ambulance clinicians, in an independent population
Impact of socioeconomic deprivation on short-term outcomes and long-term overall survival after colorectal resection for cancer.
No full textPURPOSE
The aim of this study was to assess the effects of socioeconomic deprivation on short-term outcomes and long-term overall survival following major resection of colorectal cancer (CRC) at a tertiary hospital in England.
METHOD
This was an observational cohort study of patients undergoing resection for colorectal cancer from January 2010 to December 2017. Deprivation was classified into quintiles using the English Indices of Multiple Deprivation 2010. Primary outcome was overall complications (Clavien-Dindo grades 1 to 5). Secondary outcomes were the major complications (Clavien-Dindo 3 to 5), length of hospital stay and overall survival. Outcomes were compared between most affluent group and most deprived group. Multivariate regression models were used to establish the relationship taking into account confounding variables.
RESULTS
One thousand eight hundred thirty-five patients were included. Overall and major complication rates were 44.9% and 11.5% respectively in the most affluent, and 54.6% and 15.6% in the most deprived group. Most deprived group was associated with higher overall complications (odds ratio 1.48, 95% CI 1.13-1.95, p = 0.005), higher major complications (odds ratio 1.49, 1.01-2.23, p = 0.048) and longer hospital stay (adjusted ratio 1.15, 1.06-1.25, p < 0.001) when compared with most affluent group. Median follow period was 41 months (interquartile range 20-64.5). Most deprived group had poor overall survival compared with most affluent, but it was not significant at the 5% level (hazard ratio 1.27, 0.99-1.62, p = 0.055).
CONCLUSION
Deprivation was associated with higher postoperative complications and longer hospital stay following major resection for CRC. Its relationship with survival was not statistically significant
Response to Letter to the Editor: "A Meta-Analysis of the Prevalence of Cardiac Valvulopathy in Patients With Hyperprolactinemia Treated With Cabergoline".
No full textEvaluating the learning curve for laparoscopic liver resection: a comparative study between standard and learning curve CUSUM.
No full textBACKGROUND
Laparoscopic liver resection (LLR) requires training in both hepatobiliary surgery and advanced laparoscopy. Available data on LLR learning curves are derived from pioneer surgeons. The aims of this study were to evaluate the LLR learning curve for second generation surgeons, and to compare different CUSUM methodology with and without risk adjustment.
METHODS
Retrospective analysis of a prospective database of 111 consecutive patients who underwent LLR by two surgeons at a single centre between 2011 and 2016. The LLR learning curve for minor hepatectomy (MH) was evaluated for each surgeon using standard CUSUM before and after risk-adjusting for operative difficulty using the Iwate index, and compared with Learning Curve (LC) CUSUM. The end points were operative time and conversion rate.
RESULTS
Standard CUSUM analysis identified a learning curve of 50-60 MH procedures. The corresponding learning curve reduced to 25-30 after risk-adjusting for operative difficulty, whilst LC-CUSUM identified a learning curve of 17-25 procedures.
CONCLUSIONS
The learning curve for laparoscopic minor liver resection by second generation surgeons is shorter than that for pioneer surgeons. Laparoscopic HPB fellowship programmes may further shorten the learning curve, facilitating safe expansion of LLR. The LC-CUSUM method is an alternative technique that warrants further study