Videolaryngoscopy use before and after the initial phases of the COVID-19 pandemic: The report of the VL-iCUE survey with responses from 96 countries.

BACKGROUND: The potential benefit of videolaryngoscopy use in facilitating tracheal intubation has already been established, however its use was actively encouraged during the COVID-19 pandemic as it was likely to improve intubation success and increase the patient-operator distance. OBJECTIVES: We sought to establish videolaryngoscopy use before and after the early phases of the pandemic, whether institutions had acquired new devices during the COVID-19 pandemic, and whether there had been teaching on the devices acquired. DESIGN: We designed a survey with 27 questions made available via the Joint Information Scientific Committee JISC online survey platform in English, French, Spanish, Chinese, Japanese and Portuguese. This was distributed through 18 anaesthetic and airway management societies. SETTING: The survey was open for 54 to 90 days in various countries. The first responses were logged on the databases on 28 October 2021, with all databases closed on 26 January 2022. Reminders to participate were sent at the discretion of the administering organisations. PARTICIPANTS: All anaesthetists and airway managers who received the study were eligible to participate. MAIN OUTCOME MEASURES: Videolaryngoscopy use before the COVID-19 pandemic and at the time of the survey. RESULTS: We received 4392 responses from 96 countries: 944/4336 (21.7%) were from trainees. Of the 3394 consultants, 70.8% (2402/3394) indicated no change in videolaryngoscopy use, 19.9% (675/3394) increased use and 9.3% (315/3393) reduced use. Among trainees 65.5% (618/943) reported no change in videolaryngoscopy use, 27.7% (261/943) increased use and 6.8% (64/943) reduced use. Overall, videolaryngoscope use increased by 10 absolute percentage points following the pandemic. CONCLUSIONS: Videolaryngoscopy use increased following the early phase of the COVID-19 pandemic but this was less than might have been expected.

Regular Acetaminophen Use and Blood Pressure in People With Hypertension: The PATH-BP Trial.

BACKGROUND: Acetaminophen is widely used as first-line therapy for chronic pain because of its perceived safety and the assumption that, unlike nonsteroidal anti-inflammatory drugs, it has little or no effect on blood pressure (BP). Although observational studies suggest that acetaminophen may increase BP, clinical trials are lacking. We, therefore, studied the effects of regular acetaminophen dosing on BP in individuals with hypertension. METHODS: In this double-blind, placebo-controlled, crossover study, 110 individuals were randomized to receive 1 g acetaminophen 4× daily or matched placebo for 2 weeks followed by a 2-week washout period before crossing over to the alternate treatment. At the beginning and end of each treatment period, 24-hour ambulatory BPs were measured. The primary outcome was a comparison of the change in mean daytime systolic BP from baseline to end of treatment between the placebo and acetaminophen arms. RESULTS: One-hundred three patients completed both arms of the study. Regular acetaminophen, compared with placebo, resulted in a significant increase in mean daytime systolic BP (132.8±10.5 to 136.5±10.1 mm Hg [acetaminophen] vs 133.9±10.3 to 132.5±9.9 mm Hg [placebo]; P<0.0001) with a placebo-corrected increase of 4.7 mm Hg (95% CI, 2.9-6.6) and mean daytime diastolic BP (81.2±8.0 to 82.1±7.8 mm Hg [acetaminophen] vs 81.7±7.9 to 80.9±7.8 mm Hg [placebo]; P=0.005) with a placebo-corrected increase of 1.6 mm Hg (95% CI, 0.5-2.7). Similar findings were seen for 24-hour ambulatory and clinic BPs. CONCLUSIONS: Regular daily intake of 4 g acetaminophen increases systolic BP in individuals with hypertension by ≈5 mm Hg when compared with placebo; this increases cardiovascular risk and calls into question the safety of regular acetaminophen use in this situation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01997112. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2013-003204-40.

The changing nature of HPV associated with high grade cervical lesions in vaccinated populations, a retrospective study of over 1700 cases in Scotland.

BACKGROUND: Understanding the pattern and dominance of HPV types in high grade cervical disease within increasingly vaccinated populations will help inform the development of appropriate screening and management protocols. METHODS: Over 1700 cases of cervical intraepithelial neoplasia (CIN) diagnosed between 2011 and 2017 in women younger than 25 were genotyped for HPV. Logistic regression was used to assess the association between HPV 16/18 positivity with biopsy-collection year, birth year, deprivation and vaccination status. Regression analysis was repeated for cross-protective types (31, 33 and 45). Type specific detail of non-vaccine types by vaccination status was presented descriptively. RESULTS: Detection of HPV 16/18 or 16/18/31/33 and 45 was lower in CIN2 associated with full vaccination vs no vaccination (OR 0.3; 95% CI 0.2-0.5 & 0.4; 95% CI 0.3-0.6 respectively) Similar observations were made for CIN3. The relative contribution of non-established high-risk types including those considered low risk was greater among vaccinated women with CIN2+ vs unvaccinated women with CIN2+. CONCLUSIONS: The change in HPV distribution in CIN2+ in vaccinated populations is a further marker of vaccine impact. Additionally, the progression rate of CIN2+ in vaccinated populations may be lower given the shift in type distribution. The definition of high grade disease in vaccinated populations may warrant reassessment.

Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. METHODS: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. RESULTS: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. CONCLUSIONS: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study.

BACKGROUND: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. METHODS: Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. RESULTS: Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%-42%]); possible 26 out of 151 (17% [12%-24%]); and uncertain 9 out of 43, (20% [10%-36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%-53%]); migraine aura 4 out of 38 (11% [3%-25%]); non-TIA focal symptoms 16 out of 99 (16% [10%-25%]); and no focal features 1 out of 29 (3% [0%-18%]). After MRI, a further 14 (5% [95% CI, 3-8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3-62]; P<0.0001). CONCLUSIONS: MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial.

BACKGROUND: There is a lack of evidence to guide the duration of intravenous antibiotics for bronchiectasis exacerbations. AIMS: The aim of this study was to assess whether it is feasible, based on bacterial load, to shorten intravenous antibiotics during exacerbations and whether 14 days of treatment is superior. METHODS: We recruited participants requiring intravenous antibiotics for exacerbations. Participants were randomised into two groups: to receive antibiotics for 14 days (14-day group) or to have a shorter duration of treatment based on bacterial load (bacterial load-guided group (BLGG)). Bacterial load was checked on days 0, 7, 10, 14 and 21. If the bacterial load was <106 CFU·mL-1 on day 7 or day 10 in the BLGG, antibiotics were stopped the following day. RESULTS: A total of 47 participants were in the 14-day group and 43 were in the BLGG. 88% of participants in the BLGG were able to stop antibiotics by day 8 and potentially 81% of participants in the 14-day group could have stopped antibiotics at day 8. There was a nonsignificant trend for increased clinical improvement by day 21 in the 14-day group compared to the BLGG. However, overall group data showed the median (interquartile range) time to next exacerbation was 27.5 days (12.5-60 days) in the 14-day group and 60 days (18-110 days) in the in BLGG (p=0.0034). In a Cox proportional hazard model, participants in the 14-day group were more likely to experience exacerbations (HR 1.80, 95% CI 1.16-2.80, p=0.009) than those in the BLGG, and those with mild bronchiectasis were less likely to experience exacerbations than patients with more severe bronchiectasis (HR 0.359, 95% CI 0.13-0.99, p=0.048). CONCLUSIONS: Bacterial load-guided therapy is feasible in most exacerbations requiring intravenous antibiotics. There was a nonsignificant trend for increased clinical improvement by day 21 with 14 days of antibiotics compared with bacterial load-guided therapy but paradoxically there was a prolonged time to next exacerbation in the BLGG.

One-year outcomes in a multicentre cohort study of incident rare diffuse parenchymal lung disease in children (ChILD).

We performed a prospective, observational, cohort study of children newly diagnosed with children's interstitial lung disease (ChILD), with structured follow-up at 4, 8, 12 weeks and 6 and 12 months. 127 children, median age 0.9 (IQR 0.3-7.9) years had dyspnoea (68%, 69/102), tachypnoea (75%, 77/103) and low oxygen saturation (SpO2) median 92% (IQR 88-96). Death (n=20, 16%) was the most common in those <6 months of age with SpO2<94% and developmental/surfactant disorders. We report for the first time that ChILD survivors improved multiple clinical parameters within 8-12 weeks of diagnosis. These data can inform family discussions and support clinical trial measurements.

Fluoxetine and Fractures After Stroke: Exploratory Analyses From the FOCUS Trial.

Background and Purpose- The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk. Methods- A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures. Results- Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization; 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age >70 year (hazard ratio =1.97; 95% CI, 1.13-3.45; P=0.017), female sex (hazard ratio =2.13; 95% CI, 1.29-3.51; P=0.003), and fluoxetine (hazard ratio =2.00; 95% CI, 1.20-3.34; P=0.008) were independently associated with fractures. Conclusions- Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients' function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN83290762.

Factors That Influence Confirmation of Neisseria gonorrhoeae Positivity by Molecular Methods.

Several Neisseria gonorrhoeae nucleic acid amplification tests (NAATs) with high sensitivity exist. However, the specificity of N. gonorrhoeae NAATs may be suboptimal, particularly for extragenital biospecimens. Consequently, confirmation with a second NAAT is common, although this represents a burden on resources. Furthermore, the rationale for confirmation is contentious. The objective of this work was to assess N. gonorrhoeae confirmation in over 13,000 N. gonorrhoeae screen-positive samples representing various biospecimens and three separate screening assays, the Abbott RealTime CT/NG (Abbott Molecular, Inc., Des Plaines, IL), the Cobas CT/NG test (Roche Molecular Systems Inc., Alameda, CA), and the BD ProbeTec ET CT/GC amplified DNA assay (BD Diagnostics, Sparks, MD). Factors predictive of confirmation were determined via logistic regression involving sex, year, whether the sample was formally validated, and sample site. Level of confirmation varied according to screening assay (96.2%, 86.0%, and 73.9% for the Abbott, Roche, and BD tests, respectively) in sample types formally included according to the manufacturers' instructions (i.e., validated). Sex did not affect confirmation for 2/3 assays, and the likelihood of confirmation of samples not formally included in manufacturer instructions (i.e., nonvalidated) was 89.1%, 82.1%, and 59.2% for the Abbott, Roche, and BD tests, respectively. Rectal swabs, which are nonvalidated samples, confirmed in 91.5%, 90.1%, and 87.4% of samples initially tested with the respective assays. The requirement to confirm N. gonorrhoeae in validated samples is not required for all NAATs, although initial assay-specific evaluation is justified given observed variability. Rectal samples represent robust biospecimens for N. gonorrhoeae NAAT testing and may not require confirmation when screened with the assays described.

Capillary and Venous Lactate Agreement: a pilot prospective observational study.

BACKGROUND: Blood lactate is a marker of patient illness severity. Capillary lactate (CAP-LACT) measurement can potentially improve patient screening; however, it has poor evidence of clinical utility. AIM: We aimed to investigate agreement between CAP-LACT and peripheral venous lactate (PV-LACT). METHODS: We performed a prospective observational pilot study of 99 patients requiring lactate measurement. Paired CAP-LACT and PV-LACT was recorded. Agreement was determined by Bland-Altman analysis. RESULTS: Bias was 0.2 mmol/L, with 95% limits of agreement from -1.9 to 2.3. CONCLUSIONS: CAP-LACT has poor agreement with PV-LACT. Further research is needed to improve its potential clinical utility.

Arterial lactate levels in an emergency department are associated with mortality: a prospective observational cohort study.

OBJECTIVES: Lactate measurements are routinely carried out in emergency departments and are associated with increased mortality in septic patients. However, no definitive research has been carried out into whether lactate measurements can be used as a prognostic marker in a clinically unwell population in the emergency department. METHODS: We carried out a prospective observational cohort study in consecutive patients whose arterial lactate concentration was measured in the emergency department of a tertiary referral hospital assessing 110,000 patients per year between 11th May and 11th August 2011. The main outcome measure was 30-day mortality. RESULTS: There were 120 deaths (16.1%) at 30 days postattendance in our cohort of 747 patients. Multivariate logistic regression revealed lower lactate levels were associated with 30-day survival: ORs for 30-day death compared with lactate ≥4 were 0.125 (95% CI 0.068 to 0.229) for lactate <2 and 0.273 (95% CI 0.140 to 0.533) for lactate 2-<4. Kaplan-Meier analysis showed a survival difference when dividing lactate concentrations into strata (p<0.0001). This survival difference was maintained when septic diagnoses were taken into account. CONCLUSIONS: A single arterial lactate measurement on presentation to the emergency department predicts 30-day mortality independent of other measures of illness severity.

Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation.

BACKGROUND: High-risk human papillomavirus causes cervical cancer. Vaccines have been developed that significantly reduce the incidence of preinvasive and invasive disease. This population-based observational study used linked screening, immunization, and cancer registry data from Scotland to assess the influence of age, number of doses, and deprivation on the incidence of invasive disease following administration of the bivalent vaccine. METHODS: Data for women born between January 1, 1988, and June 5, 1996, were extracted from the Scottish cervical cancer screening system in July 2020 and linked to cancer registry, immunization, and deprivation data. Incidence of invasive cervical cancer per 100 000 person-years and vaccine effectiveness were correlated with vaccination status, age at vaccination, and deprivation; Kaplan Meier curves were calculated. RESULTS: No cases of invasive cancer were recorded in women immunized at 12 or 13 years of age irrespective of the number of doses. Women vaccinated at 14 to 22 years of age and given 3 doses of the bivalent vaccine showed a significant reduction in incidence compared with all unvaccinated women (3.2/100 000 [95% confidence interval (CI) = 2.1 to 4.6] vs 8.4 [95% CI = 7.2 to 9.6]). Unadjusted incidence was significantly higher in women from most deprived (Scottish Index of Multiple Deprivation 1) than least deprived (Scottish Index of Multiple Deprivation 5) areas (10.1/100 000 [95% CI = 7.8 to 12.8] vs 3.9 [95% CI = 2.6 to 5.7]). Women from the most deprived areas showed a significant reduction in incidence following 3 doses of vaccine (13.1/100 000 [95% CI = 9.95 to 16.9] vs 2.29 [95% CI = 0.62 to 5.86]). CONCLUSION: Our findings confirm that the bivalent vaccine prevents the development of invasive cervical cancer and that even 1 or 2 doses 1 month apart confer benefit if given at 12-13 years of age. At older ages, 3 doses are required for statistically significant vaccine effectiveness. Women from more deprived areas benefit more from vaccination than those from less deprived areas.

Operative vs Nonoperative Management of Unstable Medial Malleolus Fractures: A Randomized Clinical Trial.

Importance: Unstable ankle fractures are routinely managed operatively. However, because of soft tissue and implant-related complications, recent literature has reported on the nonoperative management of well-reduced medial malleolus fractures after fibular stabilization, but with limited evidence supporting the routine application. Objective: To assess the superiority of internal fixation of well-reduced (displacement ≤2 mm) medial malleolus fractures compared with nonfixation after fibular stabilization. Design, Setting, and Participants: This superiority, pragmatic, parallel, prospective randomized clinical trial was conducted from October 1, 2017, to August 31, 2021. A total of 154 adult participants (≥16 years) with a closed, unstable bimalleolar or trimalleolar ankle fracture requiring surgery at an academic major trauma center in the UK were assessed. Exclusion criteria included injuries with no medial-sided fracture, open fractures, neurovascular injury, and the inability to comply with follow-up. Data analysis was performed in July 2022 and confirmed in September 2023. Interventions: Once the lateral (and where appropriate, posterior) malleolus had been fixed and satisfactory intraoperative reduction of the medial malleolus fracture was confirmed by the operating surgeon, participants were randomly allocated to fixation (n = 78) or nonfixation (n = 76) of the medial malleolus. Main Outcome and Measure: Olerud-Molander Ankle Score (OMAS) 1 year after randomization (range, 0-100 points, with 0 indicating worst possible outcome and 100 indicating best possible outcome). Results: Among 154 randomized participants (mean [SD] age, 56.5 [16.7] years; 119 [77%] female), 144 (94%) completed the trial. At 1 year, the median OMAS was 80.0 (IQR, 60.0-90.0) in the fixation group compared with 72.5 (IQR, 55.0-90.0) in the nonfixation group (P = .17). Complication rates were comparable. Significantly more patients in the nonfixation group developed a radiographic nonunion (20% vs 0%; P < .001), with 8 of 13 clinically asymptomatic; 1 patient required surgical reintervention for this. Fracture type and reduction quality appeared to influence fracture union and patient outcome. Conclusions and Relevance: In this randomized clinical trial comparing internal fixation of well-reduced medial malleolus fractures with nonfixation, after fibular stabilization, fixation was not superior according to the primary outcome. However, 1 in 5 patients developed a radiographic nonunion after nonfixation, and although the reintervention rate to manage this was low, the future implications are unknown. These results support selective nonfixation of anatomically reduced medial malleolar fractures after fibular stabilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03362229.

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.

BACKGROUND: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. METHODS: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. FINDINGS: The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. INTERPRETATION: Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

Ghana 3D Telemedicine International MDT: A proof-of-concept study.

A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration. METHODS: A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients. RESULTS: Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries. CONCLUSIONS: This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations.

Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

The effect of graduated compression stockings on long-term outcomes after stroke: the CLOTS trials 1 and 2.

BACKGROUND AND PURPOSE: Most randomized controlled trials of venous thromboembolism prophylaxis have focused on reduction of deep vein thrombosis, predominantly asymptomatic deep vein thrombosis, detected on imaging. We aimed to estimate the effects of graduated compression stockings on venous thromboembolism events, survival, and functional status at 6 months after stroke. METHODS: The CLOTS Trials adopted an international multicentre, parallel group design, with central randomization and a 1:1 treatment allocation. In CLOTS Trial 1, 2518 immobile stroke patients were allocated thigh-length graduated compression stockings or not, and in CLOTS trial 2, 3014 to thigh-length or below-knee graduated compression stockings. We measured vital status, Oxford Handicap Scale, and quality of life (EQ5D-3 L) at 6 months. RESULTS: We compared survival in patients enrolled in Trials 1 and 2 with a Cox proportional hazards model, including variables included in our minimization algorithm. In both trials, allocation to thigh-length graduated compression stockings was associated with a very slight, but nonsignificant, increased hazard of death in the first 6 months (Trial 1: hazard ratio, 1.087; 95% confidence interval, 0.913-1.295; and Trial 2: hazard ratio, 1.037; 95% confidence interval, 0.892-1.205). There were no statistically significant differences in venous thromboembolism events, Oxford Handicap Scale, or EQ5D-3 L between the treatment groups in CLOTS Trials 1 or 2. CONCLUSIONS: Although underpowered to detect clinically important effects on long-term outcomes, our results effectively exclude a >10% relative reduction in the hazard of death within 6 months associated with the use of thigh-length stockings. No other long-term benefits were apparent.

Agreement between L1 and E6/E7-based assays for detection of high-risk HPV in cervical, oropharyngeal and penile cancers.

AIMS: Human papillomavirus (HPV) molecular testing targets either the late gene L1 or early genes E6 and/or E7. Loss of L1 during integration is suggested to compromise sensitivity in samples associated with cancer, however, clear evidence for this is lacking. Our aim is to address this by performing a head-to-head comparison between assays targeting L1 vs E6/E7, using a series of high-grade and invasive disease samples within different biological matrices and anatomical sites. METHODS: We obtained 298 samples comprising of liquid-based cytology and biopsies of cervical cancer and cervical intraepithelial neoplasia grade 3, in addition to biopsies of penile and oropharyngeal cancers. Two commercially available HPV primary screening assays and two assays with extended genotyping were applied to the sample set targeting L1 (Abbott RealTime HR HPV Assay and Optiplex HPV Genotyping Test) and E6/E7 genes (Xpert HPV Test and EuroArray HPV Test). RESULTS: Agreement for high-risk HPV (hrHPV) for all samples types between the screening assays is over 88% and over 96% for the two genotyping assays. For HPV 16 agreement is over 90% for both screening and genotyping assays. Kappa statistics show good to very good agreement between the screening and genotyping assays for hrHPV and HPV 16. CONCLUSIONS: Analysis of the valid results from our data indicates that L1 and E6/E7 targeting assays show similar performance for detection of hrHPV in high grade cervical lesions and cancers of cervix, penis and oropharynx.

Influence of resuspension volume on dry sampling devices taken for human papillomavirus testing: implications for self-sampling.

Optimization of technical parameters that influence the performance of human papillomavirus (HPV) testing on self-taken samples is important. Here, the authors assessed the impact of resuspension volume on the detection of HPV using four validated HPV assays. Two self-sampling devices, FLOQSwabs® and Evalyn® Brushes, were inoculated with dilutions of HPV-16-positive cell line, then resuspended in various volumes of ThinPrep. The influence of vortexing during resuspension was also assessed. At target concentrations around the assay cutoff, larger volumes led to decreased HPV detection. Interestingly, the effect(s) of vortexing differed by the self-sampling device. Resuspension in 5 ml or less may maximize the detection of HPV sequences. Using a proxy of clinical material, the current observations underline the importance of optimizing preanalytical laboratory processes to support high-quality HPV testing of self-samples.

Participatory development of a 3D telemedicine system during COVID: The future of remote consultations.

BACKGROUND: The COVID pandemic brought the need for more realistic remote consultations into focus. 2D Telemedicine solutions fail to replicate the fluency or authenticity of in-person consultations. This research reports on an international collaboration on the participatory development and first validated clinical use of a novel, real-time 360-degree 3D Telemedicine system worldwide. The development of the system - leveraging Microsoft's Holoportation™ communication technology - commenced at the Canniesburn Plastic Surgery Unit, Glasgow, in March 2020. METHODS: The research followed the VR CORE guidelines on the development of digital health trials, placing patients at the heart of the development process. This consisted of three separate studies - a clinician feedback study (23 clinicians, Nov-Dec 2020), a patient feedback study (26 patients, Jul-Oct 2021), and a cohort study focusing on safety and reliability (40 patients, Oct 2021-Mar 2022). "Lose, Keep, and Change" feedback prompts were used to engage patients in the development process and guide incremental improvements. RESULTS: Participatory testing demonstrated improved patient metrics with 3D in comparison to 2D Telemedicine, including validated measures of satisfaction (p<0.0001), realism or 'presence' (Single Item Presence scale, p<0.0001), and quality (Telehealth Usability Questionnaire, p = 0.0002). The safety and clinical concordance (95%) of 3D Telemedicine with a face-to-face consultation were equivalent or exceeded estimates for 2D Telemedicine. CONCLUSIONS: One of the ultimate goals of telemedicine is for the quality of remote consultations to get closer to the experience of face-to-face consultations. These data provide the first evidence that Holoportation™ communication technology brings 3D Telemedicine closer to this goal than a 2D equivalent.