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Recovery of Surgical Training Through Extended Laparoscopic Simulation Training.
Introduction The coronavirus disease 2019 (COVID-19) pandemic has adversely affected surgical training internationally. Laparoscopic surgery has a steep learning curve necessitating repetitive procedural practice. We evaluate the efficacy of short- and long-duration simulation training on participant skill acquisition to support the recovery of surgical training. Methods A prospective, observational study involving 18 novice medical students enrolled in a five-week course. Nodal timed assessments involved three tasks: hoop placement, stacking of sugar cubes and surgical cutting. One month post-completion, we compared the ability of six novice course participants to that of six surgical trainees who completed a smaller portion of the course curriculum. Results Course participants (n=18) completed tasks 111% faster on their third and last course attempt. The surgical trainee group (n=6) took 46% longer to complete tasks compared to the six re-invited course participants, whose ability continued to advance on their fourth effort with a combined 154% earlier completion time compared to try one. Conclusions This study supports the adoption of a structured, extended, regular and spaced-out simulation course or curriculum to cultivate greater skill acquisition and retention amongst surgical trainees, and improve patient care
Treatment of chronic or relapsing COVID-19 in immunodeficiency.
BACKGROUND
Patients with some types of immunodeficiency can suffer chronic or relapsing infection with SARS-CoV-2. This leads to morbidity and mortality, infection control challenges and the risk of evolution of novel viral variants. Optimal treatment for chronic COVID-19 is unknown.
OBJECTIVE
To characterise a cohort of patients with chronic or relapsing COVID-19 disease and to record treatment response.
METHODS
We conducted a UK physician survey to collect data on underlying diagnosis and demographics, clinical features and treatment response of immune deficient patients with chronic (at least 21 days) or relapsing (at least two episodes) of COVID-19.
RESULTS
We identified 31 cases with a median age of 49 years. Underlying immune deficiency was characterised by antibody deficiency with absent or profoundly reduced peripheral B cells; prior anti-CD20 therapy and X-linked agammaglobulinemia were most common. Clinical features of COVID-19 were similar to the general population, but the median duration of symptomatic disease was 64 days (maximum 300 days) and individual patients experienced up to five episodes of illness. Remdesivir monotherapy (including when given for prolonged courses up to 20 days) was associated with sustained viral clearance in 7/23 (30.4%) clinical episodes whereas the combination of remdesivir with convalescent plasma or anti-SARS-CoV-2 monoclonal antibodies resulted in viral clearance in 13/14 (92.8%) episodes. Patients receiving no therapy did not clear SARS-CoV-2.
CONCLUSIONS
COVID-19 can present as a chronic or relapsing disease in patients with antibody deficiency. Remdesivir monotherapy is frequently associated with treatment failure, but the combination of remdesivir with antibody-based therapeutics holds promise
T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study.
Background
Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA vaccine.
Methods
We sampled health-care workers enrolled in the PITCH study across four hospital sites in the UK (Oxford, Liverpool, Newcastle, and Sheffield). All health-care workers aged 18 years or older consenting to participate in this prospective cohort study were included, with no exclusion criteria applied. Blood samples were collected where possible before vaccination and 28 (±7) days following one or two doses (given 3-4 weeks apart) of the BNT162b2 vaccine. Previous infection was determined by a documented SARS-CoV-2-positive RT-PCR result or the presence of positive anti-SARS-CoV-2 nucleocapsid antibodies. We measured spike-specific IgG antibodies and quantified T-cell responses by interferon-γ enzyme-linked immunospot assay in all participants where samples were available at the time of analysis, comparing SARS-CoV-2-naive individuals to those with previous infection.
Findings
Between Dec 9, 2020, and Feb 9, 2021, 119 SARS-CoV-2-naive and 145 previously infected health-care workers received one dose, and 25 SARS-CoV-2-naive health-care workers received two doses, of the BNT162b2 vaccine. In previously infected health-care workers, the median time from previous infection to vaccination was 268 days (IQR 232-285). At 28 days (IQR 27-33) after a single dose, the spike-specific T-cell response measured in fresh peripheral blood mononuclear cells (PBMCs) was higher in previously infected (n=76) than in infection-naive (n=45) health-care workers (median 284 [IQR 150-461] 55 [IQR 24-132] spot-forming units [SFUs] per 10 PBMCs; p<0·0001). With cryopreserved PBMCs, the T-cell response in previously infected individuals (n=52) after one vaccine dose was equivalent to that of infection-naive individuals (n=19) after receiving two vaccine doses (median 152 [IQR 119-275] 162 [104-258] SFUs/10 PBMCs; p=1·00). Anti-spike IgG antibody responses following a single dose in 142 previously infected health-care workers (median 270 373 [IQR 203 461-535 188] antibody units [AU] per mL) were higher than in 111 infection-naive health-care workers following one dose (35 001 [17 099-55 341] AU/mL; p<0·0001) and higher than in 25 infection-naive individuals given two doses (180 904 [108 221-242 467] AU/mL; p<0·0001).
Interpretation
A single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern. Future studies should determine the additional benefit of a second dose on the magnitude and durability of immune responses in individuals vaccinated following infection, alongside evaluation of the impact of extending the interval between vaccine doses.
Funding
UK Department of Health and Social Care, and UK Coronavirus Immunology Consortium
Prevalence of pouchitis in both Ulcerative Colitis and Familial Adenomatous Polyposis: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Pouchitis is a clinically significant complication of ileal pouch-anal anastomosis (IPAA) with its prevalence varying in the literature. Pouchitis is thought to occur more commonly in patients with Ulcerative Colitis (UC) than patients with Familial Adenomatous Polyposis (FAP). We conducted a systematic review with meta-analysis of all published literature to report the prevalence of pouchitis in all pouch patients as well as specifically in UC and FAP. We also investigated the prevalence of acute and chronic pouchitis in UC and FAP.
METHODS
A meta-analysis was conducted by searching the Embase, Embase classic and Pubmed databases between 1978 -2021 exploring prevalence pouchitis in UC and FAP. We then performed a random effects model in order to find the pooled prevalence of pouchitis and used odds ratios to report differences in prevalence of pouchitis in UC and FAP.
RESULTS
Fifty-nine full papers and conference abstracts were included in the meta-analysis comprising of 18,117 patients with UC and 860 with FAP. The prevalence of pouchitis in UC was 0.32 (95% CI: 0.27 - 0.37) and in FAP was found to be 0.06 (95% CI: 0.03-0.15). The odds ratio of pouchitis in UC compared with FAP patients was 4.95 (95% CI: 3.17-7.72 p<0.0001).
CONCLUSIONS
Our findings support the consensus that the prevalence of pouchitis is higher in UC than in FAP. More significantly our findings suggest that the true prevalence of pouchitis is higher than commonly reported in the literature. This literature may help counsel patients prior to undergoing restorative proctocolectomy
Three-Dimensional Endoscopic Endonasal Surgery: A Systematic Review.
OBJECTIVES
To compare participant performance and preference in the use of three-dimensional (3D) endoscopy compared to traditional two-dimensional (2D) endoscopy.
METHODS
PubMed, Embase, Medline, ClinicalKey, BMJ Case Reports, and the Cochrane library were systematically searched for English-language articles published between 2005 and 2020. Studies reporting comparisons of outcomes between 3D and 2D endoscopes were identified. Data relating to performance-related outcomes, as well as the participants' preferred endoscope were extracted, and pooled using meta-analysis models.
RESULTS
Ten studies were included in the qualitative synthesis. Six studies reported results of participants completing simulated tasks with endoscopes, while four reported full procedures. Peg transfer tasks (n = 4 cohorts) were found to be completed significantly faster with the 3D versus 2D endoscope (pooled mean difference 6.8 seconds, 95% confidence interval [CI]: 2.3-11.3), while no significant difference in times taken was observed for touch tasks (n = 4; pooled mean difference 3.7 seconds, 95% CI: -1.9 to 9.2). The secondary outcome of participant preference was reported by five studies, in which a significant preference for the 3D endoscope was observed (P = .010), with a pooled total of 72% (95% CI: 59-83) of participants preferring this to the 2D endoscope.
CONCLUSIONS
There is a growing body of evidence in support of 3D visualization in endoscopy. We have demonstrated 3D endoscopy to be associated with a significantly shorter time to performing simulated, reproducible and controlled tasks, and to be the preference of participants. This study provides grounds for further evaluation of the technology, and the potential for a greater widespread use. Laryngoscope, 2021
Study designs for comparative diagnostic test accuracy: A methodological review and classification scheme.
OBJECTIVES
(1) To identify and classify comparative diagnostic test accuracy (DTA) study designs; (2) to describe study design labels used by authors of comparative DTA studies.
METHODS
We performed a methodological review of 100 comparative DTA studies published between 2015 and 2017, randomly sampled from studies included in 238 comparative DTA systematic reviews indexed in MEDLINE in 2017. From each study report, we extracted six design elements characterizing participant flow and the labels used by authors.
RESULTS
We identified a total of 46 unique combinations of study design features in our sample, based on six design elements characterizing participant flow. We classified the studies into five study design categories based on how participants were allocated to receive each index test: 'fully paired' (n=79), 'partially paired, random subset' (n=0), 'partially paired, nonrandom subset' (n=2), 'unpaired randomized' (n=1) and 'unpaired nonrandomized' (n=3). The allocation method used in 15 studies was unclear. Sixty-one studies reported, in total, 29 unique study design labels but only four labels referred to specific design features of comparative studies.
CONCLUSION
Our classification scheme can help systematic review authors define study eligibility criteria, assess risk of bias, and communicate the strength of the evidence. A standardized labelling scheme could be developed to facilitate communication of specific design features
Persistent Hepatitis E virus infection across England and Wales 2009-2017: Demography, virology and outcomes.
The first clinical case of persistent HEV infection in England was reported in 2009. We describe the demography, virology and outcomes of patients identified with persistent HEV infection in England and Wales between 2009 and 2017. A series of 94 patients with persistent HEV infection, defined by HEV viraemia of more than 12 weeks, was identified through routine reference laboratory testing. Virology, serology and clinical data were recorded through an approved PHE Enhanced Surveillance System. Sixty-six cases (70.2%) were transplant recipients, 16 (17.0%) had an underlying haematological malignancy without stem cell transplantation, six (6.4%) had advanced HIV infection, five (5.3%) were otherwise immunosuppressed, and one patient (1.1%) had no identified immunosuppression. Retrospective analysis of 46 patients demonstrated a median 38 weeks of viraemia before diagnostic HEV testing. At initial diagnosis, 16 patients (17.0%) had no detectable anti-HEV serological response. Of 65 patients treated with ribavirin monotherapy, 11 (16.9%) suffered virological relapse despite undetectable RNA in plasma or stool at treatment cessation. Persistent HEV infection remains a rare diagnosis, but we demonstrate that a broad range of immunocompromised patients are susceptible. Both lack of awareness and the pauci-symptomatic nature of persistent HEV infection likely contribute to significant delays in diagnosis. Diagnosis should rely on molecular testing since anti-HEV serology is insufficient to exclude persistent HEV infection. Finally, despite treatment with ribavirin, relapses occur even after cessation of detectable faecal shedding of HEV RNA, further emphasising the requirement to demonstrate sustained virological responses to treatment
The evidence for assessing frailty and sarcopenia in an acute medical unit: a systematic review.
BACKGROUND/OBJECTIVES
A systematic review was conducted to assess if frailty and sarcopenia were associated with poorer outcomes in older adults admitted to an acute medical unit (AMU).
METHODS
Eligible studies included older adults with an unplanned admission to an AMU and included a measure of frailty or sarcopenia, completed within 72 hours of admission. Risk of bias was assessed.
RESULTS
Of 1659 identified articles, 16 were included (4 on sarcopenia and 12 on frailty). There was significant study heterogeneity. Overall, frailty and sarcopenia were associated with worse outcomes. Targeted interventions appeared to improve outcomes.
CONCLUSION
Current evidence suggests some benefit in screening older adults admitted to an AMU for frailty and sarcopenia. However, further studies are required before clinical adoption
Clinical, Diagnostic, and Therapeutic Aspects of Growth Hormone Deficiency During the Transition Period: Review of the Literature.
The role of growth hormone (GH) during childhood and adulthood is well established. Once final stature is reached, GH continues to act during the transition, the period between adolescence and adulthood in which most somatic and psychological development is obtained. The achievement of peak bone mass represents the most relevant aspect of GH action during the transition period; however, equally clear is its influence on body composition and metabolic profile and, probably, in the achievement of a complete gonadal and sexual maturation. Despite this, there are still some aspects that often make clinical practice difficult and uncertain, in particular in evaluating a possible persistence of GH deficiency once final stature has been reached. It is also essential to identify which subjects should undergo re-testing and, possibly, replacement therapy, and the definition of unambiguous criteria for therapeutic success. Moreover, even during the transition phase, the relationship between GH substitution therapy and cancer survival is of considerable interest. In view of the above, the aim of this paper is to clarify these relevant issues through a detailed analysis of the literature, with particular attention to the clinical, diagnostic and therapeutic aspects
Migraine: disease characterisation, biomarkers, and precision medicine.
Migraine is a disabling neurological disorder, diagnosis of which is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the heterogeneity of migraine, including the underlying genetic and neurobiological factors. This complexity has generated momentum for biomarker research to improve disease characterisation and identify novel drug targets. In this Series paper, we present the progress that has been made in the search for biomarkers of migraine within genetics, provocation modelling, biochemistry, and neuroimaging research. Additionally, we outline challenges and future directions for each biomarker modality. We also discuss the advances made in combining and integrating data from multiple biomarker modalities. These efforts contribute to developing precision medicine that can be applied to future patients with migraine