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Contact tracing strategies in household and congregate environments to identify cases of tuberculosis in low- and moderate-incidence populations.
No full textBACKGROUND
Tuberculosis is an infectious bacterial disease that is spread via respiratory droplets from infected individuals to susceptible contacts. To eliminate this disease from low- and medium-incidence settings, people who are most likely to be infected (contacts) must be identified. Recently, study authors have examined alternate approaches to contact tracing methods that demonstrate improved detection and prioritization of contacts. The comparative benefit of these methods has not been established.
OBJECTIVES
To assess the effectiveness of novel methods of contact tracing versus current standard of care to identify latent and active cases in low- to moderate-incidence settings.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, and CINAHL up to 15 July 2019. We also searched for clinical trials and examined reference lists and conference proceedings.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and cluster-RCTs of contact tracing strategies that included alternate approaches (other than standard practice).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed identified articles for eligibility and quality using prespecified criteria.
MAIN RESULTS
No trials met the inclusion criteria of this review. Several study authors described an alternate method for examining contacts and performing social network analysis but did not compare this with the current contact tracing approach.
AUTHORS' CONCLUSIONS
This Cochrane Review highlights the lack of research in support of the current contact tracing method and the need for RCTs to compare new methods such as social network analysis to improve contact tracing processes
Global smoking trends in inflammatory bowel disease: A systematic review of inception cohorts.
No full textBACKGROUND AND AIMS
The effect of smoking on the risk of developing inflammatory bowel diseases (IBD) may be heterogeneous across ethnicity and geography. Although trends in smoking for the general population are well described, it is unknown whether these can be extrapolated to the IBD cohort. Smoking prevalence trends specific to the global IBD cohort over time have not been previously reported. This is a systematic review of smoking prevalence specific to the IBD cohort across geography.
METHODS
A systematic literature search was conducted on Medline and Embase from January 1st 1946 to April 5th 2018 to identify population-based studies assessing the prevalence of smoking at diagnosis in inception cohorts of Crohn's disease(CD) or ulcerative colitis(UC). Studies that did not report smoking data from time of diagnosis or the year of IBD diagnosis were excluded. Prevalence of smoking in IBD was stratified by geography and across time.
RESULTS
We identified 56 studies that were eligible for inclusion. Smoking prevalence data at diagnosis of CD and UC was collected from twenty and twenty-five countries respectively. Never-smokers in the newly diagnosed CD population in the West has increased over the last two decades, especially in the United Kingdom and Sweden; +26.6% and +11.2% respectively. Never-smokers at CD diagnosis in newly industrialised nations have decreased over the 1990s and 2000s; China (-19.36%). Never-smokers at UC diagnosis also decreased in China; -15.4%. The former-smoker population at UC diagnosis in China is expanding; 11%(1990-2006) to 34%(2011-2013).
CONCLUSION
There has been a reduction in the prevalence of smoking in the IBD cohort in the West. This is not consistent globally. Although, smoking prevalence has decreased in the general population of newly industrialised nations, this remains an important risk factor with longer term outcomes awaiting translation in both UC and CD
Glutamate Receptor Antibodies in Autoimmune Central Nervous System Disease: Basic Mechanisms, Clinical Features, and Antibody Detection.
No full textImmune-mediated inflammation of the brain has been recognized for more than 50 years, although the initial descriptions were mainly thought to be secondary to an underlying neoplasm. Some of these paraneoplastic encephalitides express serum antibodies, but these were not thought to be pathogenic but instead have a T-cell-mediated pathophysiology. Over the last two decades, several pathogenic antibodies against neuronal surface antigens have been described in autoimmune encephalitis, which are amenable to immunotherapy. Several of these antibodies are directed against glutamate receptors (GluRs). NMDAR encephalitis (NMDARE) is the most common of these antibodies, and patients often present with psychosis, hallucinations, and reduced consciousness. Patients often progress on to develop confusion, seizures, movement disorders, autonomic instability, and respiratory depression. Although initially described as exclusively occurring secondary to ovarian teratoma (and later other tumors), non-paraneoplastic forms are increasingly common, and other triggers like viral infections are now well recognized. AMPAR encephalitis is relatively less common than NMDARE but is more likely to paraneoplastic. AMPAR antibodies typically cause limbic encephalitis, with patients presenting with confusion, disorientation, memory loss, and often seizures. The syndromes associated with the metabotropic receptor antibodies are much rarer and often can be paraneoplastic-mGluR1 (cerebellar degeneration) and mGluR5 (Ophelia syndrome) being the ones described in literature.With the advance in molecular biology techniques, it is now possible to detect these antibodies using cell-based assays with high sensitivity and specificity, especially when coupled with brain tissue immunohistochemistry and binding to live cell-based neurons. The rapid and reliable identification of these antibodies aids in the timely treatment (either in the form of identifying/removing the underlying tumor or instituting immunomodulatory therapy) and has significantly improved clinical outcome in this otherwise devastating group of conditions
Comparative value and determinants of suitability of outcome measures in treated chronic inflammatory demyelinating polyneuropathy.
No full textINTRODUCTION
The comparative value and suitability of outcome measures are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP).
METHODS
We studied 35 patients with CIDP using the Overall Neuropathy Limitation Scale (ONLS), the inflammatory Rasch-built Overall Disability Scale (I-RODS) and the Medical Research Council Sum Score (MRCSS).
RESULTS
Significant associations were determined between initial deficit and ONLS (p=0.002) and MRCSS improvement (p=0.001), but not I-RODS. A strong inverse correlation was observed between disease duration and I-RODS (p=0.002), but not ONLS/MRCSS improvement. A strong association was observed between age ≤40 years and I-RODS (p=0.001), but not ONLS/MRCSS improvement. Using minimum important differences, ONLS and I-RODS sensitivities were comparable (p=0.19).
DISCUSSION
ONLS and I-RODS are equally sensitive in identifying change. Ease of administration, better ability to detect improvement in severe disease, greater amplitude responses throughout the disease and in older subjects, favor the ONLS. The I-RODS appears more useful in early disease/younger patients. This article is protected by copyright. All rights reserved
Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.
No full textBACKGROUND
Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma.
METHODS
TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35.
FINDINGS
Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group.
INTERPRETATION
Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy.
FUNDING
UK National Institute for Health Research
Machine perfusion strategies in liver transplantation.
No full textMachine perfusion is a hot topic in liver transplantation and several new perfusion concepts are currently developed. Prior to introduction into routine clinical practice, however, such perfusion approaches need to demonstrate their impact on liver function, post-transplant complications, utilization rates of high-risk organs, and cost benefits. Therefore, based on results of experimental and clinical studies, the community has to recognize the limitations of this technology. In this review, we summarize current perfusion concepts and differences between protective mechanisms of and perfusion techniques. Next, we discuss which graft types may benefit most from perfusion techniques, and highlight the current understanding of liver viability testing. Finally, we present results from recent clinical trials involving machine liver perfusion, and analyze the value of different outcome parameters, currently used as endpoints for randomized controlled trials in the field
Unacceptable failures: the final report of the Lancet Commission into liver disease in the UK.
No full textThis final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government
Sustaining and spreading penicillin allergy de-labelling: a narrative review of the challenges for service delivery and patient safety.
No full textMany patients report allergies to penicillin, although in over 90% of these the label of penicillin allergy is shown to be incorrect following comprehensive testing. Inappropriate and inaccurate penicillin allergy labelling is a barrier to antimicrobial stewardship and can lead to patient harm. This review assesses an emergent evidence base and trend favouring de-labelling using 'direct' oral penicillin challenges following a stratified risk assessment of the likelihood and existence of true penicillin allergy, to identify and make recommendations for key components for implementation in standard practice. Research to date has focussed on the feasibility and clinical and financial outcomes of these 'direct' de-labelling strategies. There is a paucity of studies exploring the views and engagement of patients and health care professionals, and a gap in the evidence for pre-requisites to safely deliver, sustain and spread the implementation of such services across health systems