Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder.

OBJECTIVE: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Pancreatic Adenocarcinoma: Real World Evidence of Care Delivery in AccessHope Data.

BACKGROUND: Pancreatic adenocarcinoma is an aggressive disease and the delivery of comprehensive care to individuals with this cancer is critical to achieve appropriate outcomes. The identification of gaps in care delivery facilitates the design of interventions to optimize care delivery and improve outcomes in this population. METHODS: AccessHope™ is a growing organization that connects oncology subspecialists with treating providers through contracts with self-insured employers. Data from 94 pancreatic adenocarcinoma cases (August 2019-December 2022) in the AccessHope dataset were used to describe gaps in care delivery. RESULTS: In all but 6% of cases, the subspecialist provided guideline-concordant recommendations anticipated to improve outcomes. Gaps in care were more pronounced in patients with non-metastatic pancreatic cancer. There was a significant deficiency in germline testing regardless of the stage, with only 59% of cases having completed testing. Only 20% of cases were receiving palliative care or other allied support services. There was no difference in observed care gaps between patients receiving care in the community setting vs. those receiving care in the academic setting. CONCLUSIONS: There are significant gaps in the care delivered to patients with pancreatic adenocarcinoma. A concurrent subspecialist review has the opportunity to identify and address these gaps in a timely manner.

Cochlear implantation in advanced otosclerosis: utility of pre-operative radiological assessment in predicting intra-operative difficulty and final electrode position.

OBJECTIVE: This study aimed to determine if pre-operative radiological scoring can reliably predict intra-operative difficulty and final cochlear electrode position in patients with advanced otosclerosis. METHOD: A retrospective cohort study of advanced otosclerosis patients who underwent cochlear implantation (n = 48, 52 ears) was compared with a larger cohort of post-lingually deaf adult patients (n = 1414) with bilateral hearing loss and normal cochlear anatomy. Pre-operative imaging for advanced otosclerosis patients and final electrode position were scored and correlated with intra-operative difficulty and speech outcomes. RESULTS: Advanced otosclerosis patients benefit significantly from cochlear implantation. Mean duration of deafness was longer in the advanced otosclerosis group (19.5 vs 14.3 years; p < 0.05). CONCLUSION: Anatomical changes in advanced otosclerosis can result in increased difficulty of surgery. Evidence of pre-operative cochlear luminal changes was associated with intra-operative difficult insertion and final non-scala tympani position. Nearly all electrodes implanted in the advanced otosclerosis cohort were peri-modiolar. No reports of facial nerve stimulation were observed.

Relationship between in feed drugs, antibiotics and organic enrichment in marine sediments at Canadian Atlantic salmon aquaculture sites.

The presence of in-feed anti-sea lice drugs and their relationship with organic enrichment is poorly understood in sediment surrounding salmon farms. Using data from an aquaculture monitoring program (2018-2020), we describe this relationship at ten sites in four Canadian provinces. Three anti-sea lice pesticides (lufenuron, teflubenzuron, emamectin benzoate and metabolite desmethyl emamectin benzoate), and one antibiotic (oxytetracycline) were detected. Concentrations were often below limits of quantification. Values are also lower than those reported in other aquaculture salmon-producing countries. Highest concentrations, along with organic enrichment, were observed ~200 m of cages with lower concentrations detected up to 1.5 km away. Most samples had at least two drugs present: 75.2 % (British Columbia), 91.4 % (Newfoundland), and 54.8 % (New Brunswick/Nova Scotia) highlighting the potential for cumulative effects. Emamectin benzoate and oxytetracycline were detected four and three years respectively after last known treatments, demonstrating the need for research on overall persistence of compounds.

Could paraprobiotics be a safer alternative to probiotics for managing cancer chemotherapy-induced gastrointestinal toxicities?

Clinical oncology has shown outstanding progress improving patient survival due to the incorporation of new drugs. However, treatment success may be reduced by the emergency of dose-limiting side effects, such as intestinal mucositis and diarrhea. Mucositis and diarrhea management is symptomatic, and there is no preventive therapy. Bacterial and fungal-based compounds have been suggested as an alternative for preventing the development of diarrhea in cancer patients. Using probiotics is safe and effective in immunocompetent individuals, but concerns remain during immunosuppressive conditions. Paraprobiotics, formulations composed of non-viable microorganisms, have been proposed to overcome such limitation. The present literature review discusses current evidence regarding the possible use of paraprobiotics as an alternative to probiotics to prevent gastrointestinal toxicity of cancer chemotherapy.

Aerosol precautions and airway complications: a national prospective multicentre cohort study.

The perceived risk of transmission of aerosolised viral particles from patients to airway practitioners during the COVID-19 pandemic led to the widespread use of aerosol precautions, including personal protective equipment and modifications to anaesthetic technique. The risk of these aerosol precautions on peri-operative airway complications has not been assessed outside of simulation studies. This prospective, national, multicentre cohort study aimed to quantify this risk. Adult patients undergoing general anaesthesia for elective or emergency procedures over a 96-hour period were included. Data collected included use of aerosol precautions by the airway practitioner, airway complications and potential confounding variables. Mixed-effects logistic regression was used to assess the risk of individual aerosol precautions on overall and specific airway complications. Data from 5905 patients from 70 hospital sites were included. The rate of airway complications was 10.0% (95%CI 9.2-10.8%). Use of filtering facepiece class 2 or class 3 respirators was associated with an increased risk of airway complications (odds ratio 1.38, 95%CI 1.04-1.83), predominantly due to an association with difficult facemask ventilation (odds ratio 1.68, 95%CI 1.09-2.61) and desaturation on pulse oximetry (odds ratio 2.39, 95%CI 1.26-4.54). Use of goggles, powered air-purifying respirators, long-sleeved gowns, double gloves and videolaryngoscopy were not associated with any alteration in the risk of airway complications. Overall, the use of filtering facepiece class 2 or class 3 respirators was associated with an increased risk of airway complications, but most aerosol precautions used during the COVID-19 pandemic were not.

Effect of high-flow nasal oxygen on hypoxaemia during procedural sedation: a systematic review and meta-analysis.

We conducted a systematic review to evaluate the effect of high-flow nasal oxygen and conventional oxygen therapy during procedural sedation amongst adults and children. We searched MEDLINE, EMBASE and CINAHL for randomised controlled trials that reported the effects of high-flow nasal oxygen during procedural sedation. The primary outcome measure was hypoxaemia and the secondary outcomes were minimum oxygen saturation; hypercarbia; requirement for airway manoeuvres; and procedure interruptions. The quality of evidence was assessed using the revised Cochrane risk-of bias tool and grading of recommendations, assessment, development and evaluation (GRADE). Nineteen randomised controlled trials (4121 patients) including three in children were included. Administration of high-flow nasal oxygen reduced hypoxaemia, risk ratio (95%CI) 0.37 (0.24-0.56), p < 0.001; minor airway manoeuvre requirements, risk ratio (95%CI) 0.26 (0.11-0.59), p < 0.001; procedural interruptions, risk ratio (95%CI) 0.17 (0.05-0.53), p = 0.002; and increased minimum oxygen saturation, mean difference (95%CI) 4.1 (2.70-5.50), p < 0.001; as compared with the control group. High-flow nasal oxygen had no impact on hypercarbia, risk ratio (95%CI) 1.24 (0.97-1.58), p = 0.09, I2 = 0%. High-flow nasal oxygen reduced the incidence of hypoxaemia regardless of the procedure involved, degree of fractional inspired oxygen, risk-profile of patients and mode of propofol administration. The evidence was ascertained as moderate for all outcomes except for procedure interruptions. In summary, high-flow nasal oxygen compared with conventional oxygenation techniques reduced the risk of hypoxaemia, increased minimum oxygen saturation and reduced the requirement for airway manoeuvres. High-flow nasal oxygen should be considered in patients at risk of hypoxaemia during procedural sedation.

Surgical treatment of pelvic organ prolapse in women aged ≥75 years in Hong Kong: a multicentre retrospective study.

INTRODUCTION: Pelvic organ prolapse (POP) is common among older women. With the increasing lifespan and emphasis on quality of life worldwide, older women increasingly prefer surgical treatment for POP. We reviewed the surgical treatment of POP in older women to characterise its safety, effectiveness, and the type most often selected. METHODS: This multicentre, retrospective study was conducted at four hospitals between 2013 and 2018. Included patients were aged ≥75 years and had undergone POP surgery. We compared patient demographic characteristics, POP severity, and surgical outcomes between reconstructive and obliterative surgeries; these comparisons were also made among vaginal hysterectomy plus pelvic floor repair (VHPFR), transvaginal mesh surgery (TVM), vaginal hysterectomy (VH) plus colpocleisis, and colpocleisis alone. RESULTS: In total, 343 patients were included; 84.3% and 15.7% underwent reconstructive and obliterative surgeries, respectively. Overall, 246 (71.7%), 43 (12.5%), 20 (5.8%), and 34 (9.9%) patients underwent VHPFR, TVM, VH plus colpocleisis, and colpocleisis alone, respectively. Patients who were older (81.9 vs 79.6 y; P=0.001), had vault prolapse (38.9% vs 3.5%; P<0.001), and had medical co-morbidities (37% vs 4.8%; P<0.001) chose obliterative surgery more frequently than reconstructive surgery. Obliterative surgeries had shorter operative time (73.5 min vs 107 min; P<0.001) and fewer surgical complications (9.3% vs 28.0%; P=0.003). Vaginal hysterectomy plus pelvic floor repair had the highest rate of surgical complications (most were minor), while colpocleisis alone had the lowest rate (30.1% vs 8.8%; P=0.01). CONCLUSIONS: Pelvic organ prolapse surgeries were safe and effective for older women. Colpocleisis may be appropriate as primary surgery for fragile older women.

Analysis of an adaptive lead weighted ResNet for multiclass classification of 12-lead ECGs.

Background. Twelve lead ECGs are a core diagnostic tool for cardiovascular diseases. Here, we describe and analyse an ensemble deep neural network architecture to classify 24 cardiac abnormalities from 12 lead ECGs.Method. We proposed a squeeze and excite ResNet to automatically learn deep features from 12-lead ECGs, in order to identify 24 cardiac conditions. The deep features were augmented with age and gender features in the final fully connected layers. Output thresholds for each class were set using a constrained grid search. To determine why the model made incorrect predictions, two expert clinicians independently interpreted a random set of 100 misclassified ECGs concerning left axis deviation.Results. Using the bespoke weighted accuracy metric, we achieved a 5-fold cross-validation score of 0.684, and sensitivity and specificity of 0.758 and 0.969, respectively. We scored 0.520 on the full test data, and ranked 2nd out of 41 in the official challenge rankings. On a random set of misclassified ECGs, agreement between two clinicians and training labels was poor (clinician 1:κ= -0.057, clinician 2:κ= -0.159). In contrast, agreement between the clinicians was very high (κ= 0.92).Discussion. The proposed prediction model performed well on the validation and hidden test data in comparison to models trained on the same data. We also discovered considerable inconsistency in training labels, which is likely to hinder development of more accurate models.

Recruitment to higher specialty training in anaesthesia in the UK during the COVID-19 pandemic: a national survey.

There were more applications for higher specialty training posts in anaesthesia in the UK starting in August 2021 than in previous years, with approximately two-thirds being unsuccessful. We surveyed applicants to investigate their experience of the recruitment process (response rate 536/1056; 51%). Approximately 61% of respondents were not offered ST3 posts (n = 326). We enquired about their career plans for the next 12-24 months. Most respondents (79%) intended to take up a post equivalent to a third year of core training or a clinical fellow post from August 2021. Other options considered included: pursuing work abroad (17%); embarking on career breaks (16%); taking up higher training posts in intensive care medicine (15%); and permanently leaving medicine (9%). Nine per cent of respondents also expressed plans to pursue training in another medical specialty. Some expressed an intention to pursue further education or research (10%). A large proportion (42%) expressed a lack of confidence in being able to achieve the training requirements to later apply for a higher training post. The majority reported not feeling confident in achieving specialist registration in anaesthesia in the future without a training number (75%), and noted disruption to their wider life plans from the impending time out of training (78%). Sentiment analysis of free-text responses indicated generally negative sentiment about the recruitment process. Themes elicited included: feeling the recruitment process was unfair; burnout and negative impact on well-being; difficulties in making life plans; and feeling undervalued and abandoned. These results suggest that junior anaesthetic doctors in the UK negatively perceived postgraduate training structures and changes to the postgraduate curriculum and experienced difficulties in securing higher training.

Treatment threshold for intra-operative hypotension in clinical practice-a prospective cohort study in older patients in the UK.

Intra-operative hypotension frequently complicates anaesthesia in older patients and is implicated in peri-operative organ hypoperfusion and injury. The prevalence and corresponding treatment thresholds of hypotension are incompletely described in the UK. This study aimed to identify prevalence of intra-operative hypotension and its treatment thresholds in UK practice. Patients aged ≥ 65 years were studied prospectively from 196 UK hospitals within a 48-hour timeframe. The primary outcome was the incidence of hypotension (mean arterial pressure <65 mmHg; systolic blood pressure reduction >20%; systolic blood pressure <100 mmHg). Secondary outcomes included the treatment blood pressure threshold for vasopressors; incidence of acute kidney injury; myocardial injury; stroke; and in-hospital mortality. Additionally, anaesthetists providing care for included patients were asked to complete a survey assessing their intended treatment thresholds for hypotension. Data were collected from 4750 patients. Hypotension affected 61.0% of patients when defined as mean arterial pressure <65 mmHg, 91.3% of patients had >20% reduction in systolic blood pressure from baseline and 77.5% systolic blood pressure <100 mmHg. The mean (SD) blood pressure triggering vasopressor therapy was mean arterial pressure 64.2 (11.6) mmHg and the mean (SD) stated intended treatment threshold from the survey was mean arterial pressure 60.6 (9.7) mmHg. A composite adverse outcome of myocardial injury, kidney injury, stroke or death affected 345 patients (7.3%). In this representative sample of UK peri-operative practice, the majority of older patients experienced intra-operative hypotension and treatment was delivered below suggested thresholds. This highlights both potential for intra-operative organ injury and substantial opportunity for improving treatment of intra-operative hypotension.

Findings in 1,123 Men with Preoperative 68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography/Computerized Tomography and Multiparametric Magnetic Resonance Imaging Compared to Totally Embedded Radical Prostatectomy Histopathology: Implications for the Diagnosis and Management of Prostate Cancer.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized tomography (PSMA PET/CT) is recommended for staging of prostate cancer, but its additional benefit above mpMRI alone in local evaluation for prostate cancer is unclear. The study aim was to evaluate the ability of mpMRI and PSMA PET/CT individually and in combination, to predict tumor location and Gleason score ≥3+4 on robot-assisted laparoscopic radical prostatectomy (RALP) histology. MATERIALS AND METHODS: We retrospectively reviewed 1,123 men with a preoperative mpMRI and 68Ga-PSMA PET/CT prior to a RALP. Tumor locations were collected from both imaging modalities and compared to totally embedded prostate histology. Lowest apparent diffusion coefficient value on mpMRI and the highest maximum standardized uptake value (SUVmax) on 68Ga-PSMA PET/CT were collected on the index lesions to perform analysis on detection rates. RESULTS: Median prostate specific antigen was 6. Median Gleason score on biopsy and RALP histology was 4+3. The index lesion and multifocal tumor detection were similar between mpMRI and 68Ga-PSMA PET/CT (p=0.10; p=0.11). When combining mpMRI and 68Ga-PSMA PET/CT, index Gleason score ≥3+4 cancer at RALP was identified in 92%. Only 10% of patients with Gleason score ≤3+4 on biopsy with an SUVmax <5 were upgraded to ≥4+3 on RALP histology, compared to 90% if the SUVmax was >11. CONCLUSIONS: The addition of a diagnostic 68Ga-PSMA PET/CT to mpMRI can improve the detection of significant prostate cancer and improve the ability to identify men suitable for active surveillance.