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A systematic review of remote otological assessment using video-otoscopy over the past 10 years: reliability and applications.
No full textPURPOSE
This systematic review describes and evaluates the current literature on remote otological assessment using video-otoscopy with regards to reliability and potential applications.
METHODS
Systematic review was conducted in accordance with the PRISMA statement. There was heterogeneity of included studies, so a descriptive analysis was undertaken.
RESULTS
Seventeen studies were included for analysis conducted across a variety of healthcare settings. Overall, there was a trend towards acquisition of adequate images for diagnosis by non-otolaryngology-specialist facilitators with reasonable agreement between asynchronous images and controls; however, there was significant variation between the studies.
CONCLUSION
Remote otological assessment using video-otoscopy shows potential as a safe and effective method for detecting the presence of ear disease in a wide range of healthcare settings. Barriers to the acquisition of adequate images include the presence of obstructing cerumen, and strategies to deal with this should be considered. Further work is required to evaluate endoscope-based systems to assess whether they will allow the acquisition of higher quality images
The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making.
No full textBACKGROUND
Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management.
METHODS
Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item.
RESULTS
Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5-60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0-25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT.
DISCUSSION
There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes
Local Endoscopic Resection is Inferior to Gastrectomy for Early Clinical Stage T1a and T1b Gastric Adenocarcinoma: A Propensity-Matched Study.
No full textBACKGROUND
The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 gastric adenocarcinoma remains controversial. The aim of this study was to evaluate the outcome of ER versus gastrectomy in node-negative cT1a and cT1b gastric adenocarcinoma.
METHODS
Data from the National Cancer Database (2010-2015) were used to identify patients with clinical T1aN0 (n = 2927; ER: n = 1157, gastrectomy: n = 1770) and T1bN0 (n = 2915; ER: n = 474, gastrectomy: n = 2441) gastric adenocarcinoma. Propensity score matching and Cox multivariable analyses were used to account for treatment selection bias.
RESULTS
ER for cT1a and cT1b cancers was performed more frequently over time. The rates of node-positive disease in patients with cT1a and cT1b gastric adenocarcinoma were 5% and 18%, respectively. In the matched cohort, gastrectomy was associated with increased survival compared with ER for cT1a cancers (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95; p = 0.013), and corresponding 5-year survival for gastrectomy and ER was 72% and 66%, respectively (p = 0.013). For cT1b cancers, gastrectomy had a significantly longer survival compared with ER (HR 0.77, 95% CI 0.63-0.93; p = 0.008), and the corresponding 5-year survival for gastrectomy and ER was 60% and 50%, respectively (p = 0.013).
CONCLUSION
This study demonstrates ER is inferior in terms of long-term survival for clinical T1aN0 and T1bN0 gastric adenocarcinoma, despite current recommendations for ER in cT1 gastric cancers. Future research should seek to identify the subset of T1a and T1b cancers at low risk of nodal metastasis, and would thus maximally benefit from ER
Safety and efficacy of absorbable and non-absorbable fixation systems for intraperitoneal mesh fixation: an experimental study in swine.
No full textPURPOSE
Choice of the best possible fixation system in terms of safety and effectiveness for intraperitoneal mesh placement in hernia surgery remains controversial. The aim of the present study was to compare the performance of four fixation systems in a swine model of intraperitoneal mesh fixation.
METHODS
Fourteen Landrace swine were utilized in the study. The experiment included two stages. Initially, four pieces of mesh (Ventralight ™ ST) sizing 10 × 5 cm were placed and fixed intraperitoneally to reinforce 4 small full thickness abdominal wall defects created with diathermy. These defects were repaired primarily with absorbable suture before mesh implantation. Each mesh was anchored with a different tack device between Absorbatack™, Protack™, Capsure™, or Optifix™. The second stage took place after 60 days and included euthanasia, laparoscopy, and laparotomy via U-shaped incision to obtain the measurements for the outcome parameters. The primary endpoint of the study was to compare the peel strength of the compound tack/mesh from the abdominal wall. Secondary parameters were the extent and quality of visceral adhesions to the mesh, the degree of mesh shrinkage and the histological response around the tacks.
RESULTS
Thirteen out of 14 animals survived the experiment and 10 were included in the final analysis. Capsure™ tacks had higher peel strength when compared to Absorbatack™ (p = 0.028); Protack™ (p = 0.043); and Optifix™ (p = 0.009). No significant differences were noted regarding the extent of visceral adhesions (Friedman's test p value 0.854), the adhesion quality (Friedman's test p value 0.506), or the mesh shrinkage (Friedman's test p value = 0.827). Four out of the ten animals developed no adhesions at all 2 months after implantation.
CONCLUSION
Capsure™ fixation system provided higher peel strength that the other tested devices in our swine model of intraperitoneal mesh fixation. Our findings generate the hypothesis that this type of fixation may be superior in a clinical setting. Clinical trials with long-term follow-up are required to assess the safety and efficacy of mesh fixation systems in hernia surgery
Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care.
No full textBACKGROUND
Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013-2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient-perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD.
METHODS
Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood.
RESULTS
The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a 'fatal' outcome to a 'survival' outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence-such as defective interfering genomes.
CONCLUSIONS
The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis
Carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) as induction therapy for transplant-eligible, newly diagnosed multiple myeloma patients (Myeloma XI+): Interim analysis of an open-label randomised controlled trial.
No full textBACKGROUND
Carfilzomib is a second-generation irreversible proteasome inhibitor that is efficacious in the treatment of myeloma and carries less risk of peripheral neuropathy than first-generation proteasome inhibitors, making it more amenable to combination therapy.
METHODS AND FINDINGS
The Myeloma XI+ trial recruited patients from 88 sites across the UK between 5 December 2013 and 20 April 2016. Patients with newly diagnosed multiple myeloma eligible for transplantation were randomly assigned to receive the combination carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide (KRdc) or a triplet of lenalidomide, dexamethasone, and cyclophosphamide (Rdc) or thalidomide, dexamethasone, and cyclophosphamide (Tdc). All patients were planned to receive an autologous stem cell transplantation (ASCT) prior to a randomisation between lenalidomide maintenance and observation. Eligible patients were aged over 18 years and had symptomatic myeloma. The co-primary endpoints for the study were progression-free survival (PFS) and overall survival (OS) for KRdc versus the Tdc/Rdc control group by intention to treat. PFS, response, and safety outcomes are reported following a planned interim analysis. The trial is registered (ISRCTN49407852) and has completed recruitment. In total, 1,056 patients (median age 61 years, range 33 to 75, 39.1% female) underwent induction randomisation to KRdc (n = 526) or control (Tdc/Rdc, n = 530). After a median follow-up of 34.5 months, KRdc was associated with a significantly longer PFS than the triplet control group (hazard ratio 0.63, 95% CI 0.51-0.76). The median PFS for patients receiving KRdc is not yet estimable, versus 36.2 months for the triplet control group (p < 0.001). Improved PFS was consistent across subgroups of patients including those with genetically high-risk disease. At the end of induction, the percentage of patients achieving at least a very good partial response was 82.3% in the KRdc group versus 58.9% in the control group (odds ratio 4.35, 95% CI 3.19-5.94, p < 0.001). Minimal residual disease negativity (cutoff 4 × 10-5 bone marrow leucocytes) was achieved in 55% of patients tested in the KRdc group at the end of induction, increasing to 75% of those tested after ASCT. The most common adverse events were haematological, with a low incidence of cardiac events. The trial continues to follow up patients to the co-primary endpoint of OS and for planned long-term follow-up analysis. Limitations of the study include a lack of blinding to treatment regimen and that the triplet control regimen did not include a proteasome inhibitor for all patients, which would be considered a current standard of care in many parts of the world.
CONCLUSIONS
The KRdc combination was well tolerated and was associated with both an increased percentage of patients achieving at least a very good partial response and a significant PFS benefit compared to immunomodulatory-agent-based triplet therapy.
TRIAL REGISTRATION
ClinicalTrials.gov ISRCTN49407852
Protocol for a multi-site pilot and feasibility randomised controlled trial: Surgery versus PhysiothErapist-leD exercise for traumatic tears of the rotator cuff (the SPeEDy study).
No full textBACKGROUND
Clinically, a distinction is made between types of rotator cuff tear, traumatic and non-traumatic, and this sub-classification currently informs the treatment pathway. It is currently recommended that patients with traumatic rotator cuff tears are fast tracked for surgical opinion. However, there is uncertainty about the most clinically and cost-effective intervention for patients with traumatic rotator cuff tears and further research is required. SPeEDy will assess the feasibility of a fully powered, multi-centre randomised controlled trial (RCT) to test the hypothesis that, compared to surgical repair (and usual post-operative rehabilitation), a programme of physiotherapist-led exercise is not clinically inferior, but is more cost-effective for patients with traumatic rotator cuff tears.
METHODS
SPeEDy is a two-arm, multi-centre pilot and feasibility RCT with integrated Quintet Recruitment Intervention (QRI) and further qualitative investigation of patient experience. A total of 76 patients with traumatic rotator cuff tears will be recruited from approximately eight UK NHS hospitals and randomly allocated to either surgical repair and usual post-operative rehabilitation or a programme of physiotherapist-led exercise. The QRI is a mixed-methods approach that includes data collection and analysis of screening logs, audio recordings of recruitment consultations, interviews with patients and clinicians involved in recruitment, and review of study documentation as a basis for developing action plans to address identified difficulties whilst recruitment to the RCT is underway. A further sample of patient participants will be purposively sampled from both intervention groups and interviewed to explore reasons for initial participation, treatment acceptability, reasons for non-completion of treatment, where relevant, and any reasons for treatment crossover.
DISCUSSION
Research to date suggests that there is uncertainty regarding the most clinically and cost-effective interventions for patients with traumatic rotator cuff tears. There is a clear need for a high-quality, fully powered, RCT to better inform clinical practice. Prior to this, we first need to undertake a pilot and feasibility RCT to address current uncertainties about recruitment, retention and number of and reasons for treatment crossover.
TRIAL REGISTRATION
ClinicalTrials.gov ( NCT04027205 ) - Registered on 19 July 2019. Available via
Common General Surgical Never Events: Analysis of NHS England Never Events Data.
No full textBACKGROUND
There is little available data on common general surgical Never Events (NE). Lack of this information may have affected our attempts to reduce the incidence of these potentially serious clinical incidents. The purpose of this study was to identify common general surgical NE from the data held by the National Health Service (NHS) England.
METHODS
We analysed NHS England NE data from April 2012 to February 2020 to identify common general surgical NE.
RESULTS
There was a total of 797 general surgical NE identified under three main categories of Wrong-Site Surgery (n=427;53.58%), Retained Items Post-Procedure (n=355; 44.54%), and Wrong Implant/Prosthesis and (n=15; 1.88%). We identified a total of 56 common general surgical themes - 25 each in the Wrong-Site Surgery and Retained Foreign Body category and 6 in wrong implants.Wrong skin condition surgery was the commonest wrong-site surgery (n=117; 27.4%). There were 18 wrong side chest drains (4.2%) and 18 (4.2%) wrong side angioplasty/angiogram. There were 7 (1.6%) instances of confusion in pilonidal/perianal/perineal surgeries and 6 (1.4%) instances of biopsy of cervix rather than colon or rectum.Retained surgical swabs were the most common retained items (n=165;46.5%). There were 28 (7.9%) laparoscopic retrieval bags with or without the specimen, 26 (7.3%) chest drain guidewires, 26 (7.3%) surgical needles; and 9 (2.5%) surgical drains. Wrong stents were most common (n=9;60%) wrong implant followed by wrong breast implants (n=2;13.3%).
CONCLUSION
This study found 56 common general surgical Never Events. This information is not available to surgeons around the world. Increased awareness of these common themes of NE may allow for adoption of more effective, specific safeguards and ultimately help reduce their incidence
Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues.
No full textType 2 Diabetes Mellitus (T2DM) is a chronic inflammatory disorder that is characterized by chronic hyperglycemia and impaired insulin signaling which in addition to be caused by common metabolic dysregulations, have also been associated to changes in various immune cell number, function and activation phenotype. Obesity plays a central role in the development of T2DM. The inflammation originating from obese adipose tissue develops systemically and contributes to insulin resistance, beta cell dysfunction and hyperglycemia. Hyperglycemia can also contribute to chronic, low-grade inflammation resulting in compromised immune function. In this review, we explore how the trafficking of innate and adaptive immune cells under inflammatory condition is dysregulated in T2DM. We particularly highlight the obesity-related accumulation of leukocytes in the adipose tissue leading to insulin resistance and beta-cell dysfunction and resulting in hyperglycemia and consequent changes of adhesion and migratory behavior of leukocytes in different vascular beds. Thus, here we discuss how potential therapeutic targeting of leukocyte trafficking could be an efficient way to control inflammation as well as diabetes and its vascular complications