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Hypophosphatasia mimicking hypoxic-ischaemic encephalopathy: early recognition and management.
No full textBACKGROUND
Hypophosphatasia (HPP) is a rare inherited disorder affecting bone and teeth development. Perinatal HPP is the most severe form and associated with a high mortality. Features include respiratory distress, skeletal abnormalities and low alkaline phosphatase (ALP) activity.
CASE
A baby boy developed respiratory distress, hypotonia and seizures within an hour of birth. Blood gas showed mixed acidosis and abnormal base deficit. Hypoxic-ischaemic encephalopathy (HIE) was suspected and managed with therapeutic hypothermia. Subsequent investigations identified low ALP activity and abnormal bone mineralisation, leading to a diagnosis of HPP. On day 5 of life, enzyme replacement therapy (ERT) was commenced, its first use via direct NHS England funding since UK licensing in 2017.
CONCLUSIONS
Early hypotonia is an atypical presentation for perinatal HPP. Combined with acidosis and encephalopathy, it can clinically mimic HIE. Early recognition of biochemical and radiological features of HPP is essential for rapid diagnosis and timely initiation of life-saving ERT
Management of atrial fibrillation in patients with chronic kidney disease in clinical practice: a joint European Heart Rhythm Association (EHRA) and European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) physician-based survey.
No full textThe European Heart Rhythm Association (EHRA) and European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) jointly conducted a physician-based survey to gain insight into the management of atrial fibrillation (AF) in patients with chronic kidney disease (CKD) and adherence to current European Society of Cardiology AF Guidelines in contemporary clinical practice. Physician-based survey conducted during an 8-week period using an internet-based questionnaire sent to all EHRA and ERA/EDTA members, with voluntary and anonymous responses. Among 306 physicians (160 EHRA and 146 ERA/EDTA members; 56 countries), a multidisciplinary team for management of AF-CKD patients was available to only 20/300 respondents (6.7%) and 132/295 (44.7%) routinely screened CKD patients for AF. Oral anticoagulation (OAC) use was based on individual stroke risk in mild/moderate CKD but on shared decision-making in advanced CKD. The CHA2DS2-VASc score-based decisions were more common among cardiologists, with substantial intra- and inter-specialty heterogeneity in the use and dosing of specific OAC drugs across CKD stages, heterogeneous strategies for OAC monitoring (especially among nephrologists) and a modest impact of CKD on rate and rhythm control treatment decisions. The HAS-BLED score was generally not a determinant of OAC prescribing. Our survey provided important insights into contemporary management of AF patients with CKD in clinical practice, revealing certain differences between nephrologists and cardiologists and highlighting shared and specific knowledge gaps and unmet needs. These findings emphasize the need for streamlining the care for AF patients across different specialties and may inform development of tailored education interventions
Clinical Potential of Targeting Fibroblast Growth Factor-23 and αKlotho in the Treatment of Uremic Cardiomyopathy.
No full textChronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor-23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor-23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end-stage renal disease
Impact of a simulation-based induction programme in gastroscopy on trainee outcomes and learning curves.
No full textBACKGROUND
Pre-clinical simulation-based training (SBT) in endoscopy has been shown to augment trainee performance in the short-term, but longer-term data are lacking.
AIM
To assess the impact of a two-day gastroscopy induction course combining theory and SBT (Structured PRogramme of INduction and Training - SPRINT) on trainee outcomes over a 16-mo period.
METHODS
This prospective case-control study compared outcomes between novice SPRINT attendees and controls matched from a United Kingdom training database. Study outcomes comprised: (1) Unassisted D2 intubation rates; (2) Procedural discomfort scores; (3) Sedation practice; (4) Time to 200 procedures; and (5) Time to certification.
RESULTS
Total 15 cases and 24 controls were included, with mean procedure counts of 10 and 3 ( = 0.739) pre-SPRINT. Post-SPRINT, no significant differences between the groups were detected in long-term D2 intubation rates ( = 0.332) or discomfort scores ( = 0.090). However, the cases had a significantly higher rate of unsedated procedures than controls post-SPRINT (58% 44%, = 0.018), which was maintained over the subsequent 200 procedures. Cases tended to perform procedures at a greater frequency than controls in the post-SPRINT period (median: 16.2 13.8 per mo, = 0.051), resulting in a significantly greater proportion of cases achieving gastroscopy certification by the end of follow up (75% 36%, = 0.017).
CONCLUSION
In this pilot study, attendees of the SPRINT cohort tended to perform more procedures and achieved gastroscopy certification earlier than controls. These data support the role for wider evaluation of pre-clinical induction involving SBT
Predicting recurrent atrial fibrillation after catheter ablation: a systematic review of prognostic models.
No full textAIMS
We assessed the performance of modelsf (risk scores) for predicting recurrence of atrial fibrillation (AF) in patients who have undergone catheter ablation.
METHODS AND RESULTS
Systematic searches of bibliographic databases were conducted (November 2018). Studies were eligible for inclusion if they reported the development, validation, or impact assessment of a model for predicting AF recurrence after ablation. Model performance (discrimination and calibration) measures were extracted. The Prediction Study Risk of Bias Assessment Tool (PROBAST) was used to assess risk of bias. Meta-analysis was not feasible due to clinical and methodological differences between studies, but c-statistics were presented in forest plots. Thirty-three studies developing or validating 13 models were included; eight studies compared two or more models. Common model variables were left atrial parameters, type of AF, and age. Model discriminatory ability was highly variable and no model had consistently poor or good performance. Most studies did not assess model calibration. The main risk of bias concern was the lack of internal validation which may have resulted in overly optimistic and/or biased model performance estimates. No model impact studies were identified.
CONCLUSION
Our systematic review suggests that clinical risk prediction of AF after ablation has potential, but there remains a need for robust evaluation of risk factors and development of risk scores
Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection.
No full textBACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point-of-care antigen and molecular tests to detect current SARS-CoV-2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory-based diagnostic methods, with the aim of reducing household and community transmission.
OBJECTIVES
To assess the diagnostic accuracy of point-of-care antigen and molecular-based tests to determine if a person presenting in the community or in primary or secondary care has current SARS-CoV-2 infection.
SEARCH METHODS
On 25 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.
SELECTION CRITERIA
We included studies of people with suspected current SARS-CoV-2 infection, known to have, or not to have SARS-CoV-2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point-of-care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction (RT-PCR) tests and established clinical diagnostic criteria).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS-2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular-based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer.
MAIN RESULTS
We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS-CoV-2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in-house antigen test. Five of the studies included were only available as preprints. We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over-sampling of samples with confirmed COVID-19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT-PCR to confirm the absence of COVID-19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations. Antigen tests Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test. Rapid molecular assays Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID-19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%). Individual tests We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of -2.8% (95% CI -6.4 to 0.8)) AUTHORS' CONCLUSIONS: This review identifies early-stage evaluations of point-of-care tests for detecting SARS-CoV-2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID-19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT-PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice. Prospective and comparative evaluations of rapid tests for COVID-19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point-of-care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline
Preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA): explanation, elaboration, and checklist.
No full textThe weekend effect - How can it be mitigated? Introduction of a consultant-delivered emergency general surgical service.
No full textBackground
Poorer patient outcomes for emergency general surgery have been observed in patients admitted to hospital over the weekend. This paper reports the outcomes of a Consultant-delivered service model for weekend admissions and its impact for patients undergoing emergency laparotomy.
Methods
Operative data was analysed from a prospectively collected database over 5-years. Primary outcome measures were 30-day all-cause mortality and Clavien-Dindo class ≥2 morbidity. Secondary outcomes included time from admission to diagnostic imaging and time to surgery, post-operative length of stay and requirement for Intensive Care Unit admission.
Results
263 patients underwent an emergency laparotomy. Overall 30-day mortality was 4.6% and all-cause morbidity was 55.9%. The most common indications for laparotomy were mechanical small bowel obstruction (32.7%) and hollow viscus perforation (30.4%) of the 263 emergency laparotomies, 92 patients in the cohort were weekend admissions (Saturday or Sunday). There was no significant difference amongst patients admitted during the weekend in ASA grade, age, gender, or proportion of patients receiving a pre-operative computed tomography scan, when compared to those during the week. Compared to weekdays, weekend admission was not associated with a significant difference in mortality (5.3% and 3.3%, respectively p = 0.458), all-cause morbidity (p = 0.509), post-operative length of stay (p = 0.681), or Intensive Care Unit admission (p = 0.761).
Conclusion
A Consultant Surgeon delivered emergency service can avoid the poor patient outcomes associated with weekend admissions and the 'weekend effect'
Hearing outcome measures for conductive and mixed hearing loss treatment in adults: a scoping review.
No full textOBJECTIVE
Rehabilitation options for conductive and mixed hearing loss are continually expanding, but without standard outcome measures comparison between different treatments is difficult. To meaningfully inform clinicians and patients core outcome sets (COS), determined via a recognised methodology, are needed. Following our previous work that identified hearing, physical, economic and psychosocial as core areas of a future COS, the AURONET group reviewed hearing outcome measures used in existing literature and assigned them into different domains within the hearing core area.
DESIGN
Scoping review.
STUDY SAMPLE
Literature including hearing outcome measurements for the treatment of conductive and/or mixed hearing loss.
RESULTS
The literature search identified 1434 studies, with 278 subsequently selected for inclusion. A total of 837 hearing outcome measures were reported and grouped into nine domains. The largest domain constituted pure-tone threshold measurements accounting for 65% of the total outcome measures extracted, followed by the domains of speech testing (20%) and questionnaires (9%). Studies of hearing implants more commonly included speech tests or hearing questionnaires compared with studies of middle ear surgery.
CONCLUSIONS
A wide range of outcome measures are currently used, highlighting the importance of developing a COS to inform individual practice and reporting in trials/research
