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The amygdala is a medial temporal lobe structure known to be involved in processing emotional conflict. However, its role in processing non-emotional conflict is not well understood. Previous studies have utilized the Stroop Task to examine brain modulation of humans under the color-word conflict scenario, which is non-emotional conflict processing, and found hippocampal theta-band (4-7 Hz) modulation. This study aims to survey amygdaloid theta power changes during non-emotional conflict processing using intracranial depth electrodes in nine epileptic patients (3 female; age 20-62). All patients were asked to perform a modified Stroop task. During task performance, local field potential (LFP) data was recorded from macro contacts sampled at 2 K Hz and used for analysis. Mean theta power change from baseline was compared between the incongruent and congruent task condition groups using a paired sample t-test. Seven patients were available for analysis after artifact exclusion. In five out of seven patients, statistically significant increases in theta-band power from baseline were noted during the incongruent task condition (paired sample t-test p 0.001), including one patient exhibiting theta power increases in both task conditions. Average response time was 1.07 s (failure trials) and 1.04 s (success trials). No speed-accuracy tradeoff was noted in this analysis. These findings indicate that human amygdaloid theta-band modulation may play a role in processing non-emotional conflict. It builds directly upon work suggesting that the amygdala processes emotional conflict and provides a neurophysiological mechanism for non-emotional conflict processing as well.

Summary Background Chest x-rays are widely used in clinical practice; however, interpretation can be hindered by human error and a lack of experienced thoracic radiologists. Deep learning has the potential to improve the accuracy of chest x-ray interpretation. We therefore aimed to assess the accuracy of radiologists with and without the assistance of a deep-learning model. Methods In this retrospective study, a deep-learning model was trained on 821 681 images (284 649 patients) from five data sets from Australia, Europe, and the USA. 2568 enriched chest x-ray cases from adult patients (≥16 years) who had at least one frontal chest x-ray were included in the test dataset; cases were representative of inpatient, outpatient, and emergency settings. 20 radiologists reviewed cases with and without the assistance of the deep-learning model with a 3-month washout period. We assessed the change in accuracy of chest x-ray interpretation across 127 clinical findings when the deep-learning model was used as a decision support by calculating area under the receiver operating characteristic curve (AUC) for each radiologist with and without the deep-learning model. We also compared AUCs for the model alone with those of unassisted radiologists. If the lower bound of the adjusted 95% CI of the difference in AUC between the model and the unassisted radiologists was more than −0·05, the model was considered to be non-inferior for that finding. If the lower bound exceeded 0, the model was considered to be superior. Findings Unassisted radiologists had a macroaveraged AUC of 0·713 (95% CI 0·645–0·785) across the 127 clinical findings, compared with 0·808 (0·763–0·839) when assisted by the model. The deep-learning model statistically significantly improved the classification accuracy of radiologists for 102 (80%) of 127 clinical findings, was statistically non-inferior for 19 (15%) findings, and no findings showed a decrease in accuracy when radiologists used the deep-learning model. Unassisted radiologists had a macroaveraged mean AUC of 0·713 (0·645–0·785) across all findings, compared with 0·957 (0·954–0·959) for the model alone. Model classification alone was significantly more accurate than unassisted radiologists for 117 (94%) of 124 clinical findings predicted by the model and was non-inferior to unassisted radiologists for all other clinical findings. Interpretation This study shows the potential of a comprehensive deep-learning model to improve chest x-ray interpretation across a large breadth of clinical practice. Funding Annalise.ai.

OBJECTIVES Cerebrospinal fluid (CSF) leaks and meningoencephaloceles originating in the lateral recess of the sphenoid sinus can be challenging. The traditional transpterygoid approach through the pterygopalatine fossa (PPF) is time consuming and places important structures at risk, which can lead to significant morbidity. We report a multi-institutional experience using a simplified, endoscopic modified transpterygoid approach (MTPA), which spares the PPF contents in the management of lateral sphenoid sinus meningoencephaloceles and CSF leaks. STUDY DESIGN Multi-Institutional, Retrospective Case Series. METHODS Patients with lateral sphenoid recess CSF leaks and meningoencephaloceles between 2014 and 2020 who underwent the MTPA at two academic medical centers were identified. Repair techniques and outcomes were evaluated. RESULTS Thirty-three patients underwent the MTPA for management. Skull base reconstruction was performed using a free mucosal graft (24/33, 72.7%), nasoseptal flap (4/33, 12.1%), bone grafts (3/33, 9.1%), and abdominal fat grafts (2/33, 6.1%). Lumbar drains and perioperative intracranial pressure measurements were routinely employed. Postoperative complications were uncommon and included three patients (9.7%) with temporary V2 anesthesia, one patient (3.2%) with prolonged V2 anesthesia, and one patient (3.2%) with subjective dry eye, all of which resolved at 9 months postoperatively. There were no recurrent CSF leaks resulting in a 100% success rate. Average follow-up was 13 months. CONCLUSION The MTPA reduces morbidity and greatly simplifies access to the lateral sphenoid sinus for the management of CSF leaks and meningoencephaloceles, without compromising exposure. This technique avoids the need for extensive PPF dissection and should be considered for the management of benign lesions involving the lateral sphenoid sinus. LEVEL OF EVIDENCE 4 Laryngoscope, 131:2224-2230, 2021.

Vancomycin plus piperacillin–tazobactam (VPT) is a commonly used antimicrobial regimen for septic patients. VPT is more nephrotoxic than other regimens such as vancomycin plus cefepime (VC) when given over several days. This risk of nephrotoxicity is less clear when VPT is given for initial empiric therapy in sepsis and de-escalated quickly based on evolving clinical information. The objective of this study was to assess nephrotoxicity among septic patients empirically treated with either VPT or VC at initial clinical presentation. We conducted a retrospective study of septic patients who received VPT or VC within 12 h of presentation to the emergency department. The primary outcomes were acute kidney injury (AKI) and renal recovery 72 h after presentation. For the total of 418 patients, 306 received VPT and 112 received VC. Rates of AKI at 72 h were 15.2% for VPT patients and 11.0% for VC patients [p = 0.44]. Among patients with AKI at presentation, 16.3% of VPT patients had AKI at 72 h compared to 8.9% of VC patients [p = 0.19]. Among those without AKI at presentation, 14.2% VPT patients and 16.7% VC patients had AKI at 72 h [p = 0.71]. Renal recovery rates for patients with AKI at presentation were 42.3% for VPT patients versus 40.3% for VC patients [p = 0.78]. In-hospital renal replacement therapy occurred in 6.2% VPT patients and 0.9% VC patients [p = 0.024]. Therefore, initial empiric therapy with VPT in sepsis may not confer increased risk of AKI when de-escalated appropriately.

Background Post-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects Objective/hypothesis To test the use of ECT to disrupt the reconsolidation of traumatic memories as a potential treatment for PTSD Methods Participants were adults from the civilian population and were referred for ECT treatment for severe depression with comorbid PTSD symptoms. Twenty-eight participants were randomly assigned to reactivation of a traumatic or non-traumatic memory using audio script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included a comparison of the change in heart rate while listening to the script Results Twenty-five female patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time Conclusions ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT with non-traumatic memory reactivation. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04027452 . Identifier NCT04027452.

Summary Background The vertical rectus abdominis myocutaneous (VRAM) flap is an established technique employed to reconstruct pelvic and perineal defects not amenable to primary closure. The aim of this study was to systematically review the morbidity of VRAM flap reconstruction following exenterative pelvic surgery. Materials and methods A systematic literature search was conducted by using Medline, EMBASE, and Cochrane databases. Abstracts of all studies published from inception to November 2019 were identified. Search terms used included ‘vertical rectus abdominis myocutaneous’, ‘vertical rectus abdominis musculocutaneous’ and ‘VRAM’. Only studies that described outcomes when a VRAM flap was used during exenterative pelvic surgery were included; case reports were excluded. The primary outcome measure was VRAM flap morbidity. Secondary outcome measures included donor site morbidity and hospital length of stay. Results Sixty-five studies with a total of 1827 patients were identified and included. Perineal reconstruction was most commonly performed following abdominal perineal excision of the rectum (APER) (n = 636 and 34.8%). Median patient age at surgery ranged from 38 to 78 years. Mean perineal flap morbidity was 27%, with a complete flap loss rate of 1.8% and a perineal hernia rate of 0.2%. Mean donor site morbidity was 15%, with an abdominal dehiscence rate of 5.5% and an incisional hernia rate of 3.3%. Conclusions While overall morbidity after VRAM flap reconstruction in pelvic visceral surgery is high; the risk of major complications remains low. These data are important when counselling patients for surgery.

Objectives Diabetes mellitus (DM) is a serious public health issue worldwide, and DM patients have higher risk of cardiovascular diseases (CVDs), which is the leading cause of DM-related deaths. China has the largest DM population, yet a robust model to predict CVDs in Chinese DM patients is still lacking. This systematic review is carried out to summarize existing models and identify potentially important predictors for CVDs in Chinese DM patients. Study design Systematic review. Methods Medline and Embase were searched for data from April 1st, 2011 to May 31st, 2018. A study was eligible if it developed CVD (defined as total CVD or any major cardiovascular component) risk prediction models or explored potential predictors of CVD specifically for Chinese people with type 2 DM. Standardized forms were utilized to extract information, appraise applicability, risk of bias, and availabilities. Results Five models and 29 studies focusing on potential predictors were identified. Models for a primary care setting, or to predict total CVD, are rare. A number of common predictors (e.g. age, sex, diabetes duration, smoking status, glycated hemoglobin (HbA1c), blood pressure, lipid profile, and treatment modalities) were observed in existing models, in which urine albumin:creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) are highly recommended for the Chinese population. Variability of blood pressure (BP) and HbA1c should be included in prediction model development as novel factors. Meanwhile, interactions between age, sex, and risk factors should also be considered. Conclusions A 10-year prediction model for CVD risk in Chinese type 2 DM patients is lacking and urgently needed. There is insufficient evidence to support the inclusion of other novel predictors in CVDs risk prediction functions for routine clinical use.

To revisit the population norms of health-related quality of life (HRQoL) and health utility for the Hong Kong general population, compare these scores over past health surveys, and assess the association of scores with non-communicable diseases (NCDs) and their risk factors. HRQoL data measured by the standard Short Form 12 Health Survey-version 2 (SF-12v2) were extracted from the surveys in 1998, 2003/2004, 2008/2009 and 2014/2015. SF-12v2 data were mapped to the Short-form 6-dimension (SF-6D) preference-based measure to generate the health utility scores. Population weighting based on the sex and age in the second quarter of 2015 was applied when generating population normative values. Linear regression models were fitted to assess the effect of the number of NCDs and modifiable lifestyle factors on HRQoL and health utility. The general population mean scores of SF-12v2 domains and SF-6D in 2014/15 were higher compared to past surveys. Linear increases in General Health, Vitality and Mental Health domains were observed from 1998 to 2014/15. More doctor-diagnosed NCDs, insufficient physical activity and fruit/vegetable consumption, poor sleep quality and insufficient or excessive amount of sleep (

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute treatment, there are no published studies of continuation MST for the prevention of relapse. Methods: Patients with TRD with a DSM-IV diagnosis of major depressive disorder or bipolar disorder who met response criteria after acute MST were offered continuation MST in a prospective, open-label trial between February 2012 and June 2019. They received 12 continuation MST sessions with decreasing frequency over the course of 6 months, with additional booster sessions if their depression symptoms started to worsen. The primary outcome was relapse of depression or psychiatric hospitalization. Secondary outcomes included relapse of suicidal ideation and neurocognitive outcomes. Results: Thirty participants completing at least one assessment during continuation MST were included in the analysis; 10 (33.3%) relapsed, with no significant differences in survival distributions between unipolar and bipolar groups (χ2 = 0.3, P = .58). Mean (SD) survival time was 18.6 (1.6) weeks. All 17 participants who achieved resolution of baseline suicidality after acute MST remained free of suicidality during the continuation phase. Except for improvement in verbal fluency, neurocognitive test scores did not change during continuation MST. Conclusions: During 6 months of continuation MST, two-thirds of participants sustained improvements in depressive symptoms without any adverse cognitive effects. Future studies of continuation MST are warranted, particularly in comparison to ECT. Trial Registration: ClinicalTrials.gov identifier: NCT01596608.

Aims The COVID-19 pandemic necessitated introduction of revised diagnostic pathways for assessing Urgent Suspected Cancer (USC) referrals. Combinations of FIT and MPCT were used to manage referrals and prioritise access to clinical services or invasive tests. The effectiveness of these pathways are evaluated in this study. Methods All consecutive patients referred from primary care on the USC pathway between 15th March – 15th June 2020 were included to reflect the effect of full lockdown measures. Data collected included demographics, presenting symptom(s), investigations and timelines and patient outcomes up to 90 days following initial referral. Results 816 patients across 8 sites in Wales were included in this initial analysis. 52.7% of patients were female with median age 69 (21 – 97) years. Of the 50.7% who had first-line clinical review, 70.5% were virtual consultations. 49.3% had primary investigations, with FIT in 31% of patients and MPCT in 18.3%. This was compliant with locally agreed pathways for 77.3% of referrals. COVID-response pathways achieved a 28.5% reduction in use of colonoscopy as first-line investigation and 84.3% of patients avoided face-to-face consultations altogether during this first wave of the pandemic. Overall, 5.6% of USC referrals were diagnosed with CRC. Median timescale from diagnosis to treatment for CRC was 82 (4 – 175) days. The NPV for FIT in this cohort was 99.5%. MPCT as the first modality had a NPV of 99%. Conclusion A modified investigation pathway maintained cancer diagnosis during the pandemic with improved resource utilisation to that used previously.

Background The COVID‐19 pandemic has been associated with excess mortality and reduced emergency department attendance. However, the effect of varying wave periods of COVID‐19 on in‐hospital mortality and length of stay (LOS) for non‐COVID disease for non‐COVID diseases remains unexplored. Methods We examined a territory‐wide observational cohort of 563,680 emergency admissions between January 1 and November 30, 2020, and 709,583 emergency admissions during the same 2019 period in Hong Kong, China. Differences in 28‐day in‐hospital mortality risk and LOS due to COVID‐19 were evaluated. Results The cumulative incidence of 28‐day in‐hospital mortality increased overall from 2.9% in 2019 to 3.6% in 2020 (adjusted hazard ratio [aHR] = 1.22, 95% CI 1.20 to 1.25). The aHR was higher among patients with lower respiratory tract infection (aHR: 1.30 95% CI 1.26 to 1.34), airway disease (aHR: 1.35 95% CI 1.22 to 1.49), and mental disorders (aHR: 1.26 95% CI 1.15 to 1.37). Mortality risk in the first‐ and third‐wave periods was significantly greater than that in the inter‐wave period (p‐interaction

EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health [MC_PC_19004], which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. UA, CM, AA-L, and AFF acknowledge funding from Chief Scientist Office Rapid Research in COVID-19 programme (COV/SAN/20/06) and Health Data Research UK (measuring and understanding multimorbidity using routine data in the UK—HDR-9006; CFC0110). SVK acknowledges funding from a NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and the Scottish Government's Chief Scientist Office (SPHSU17). SJS is funded by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z). Background The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020–21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals. Methods We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type. Findings Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine—841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (

Background Aneurysmal subarachnoid hemorrhage (aSAH) requires complex multidisciplinary care. After initial treatment (index hospital), readmission to a different hospital (nonindex) can compromise quality of care, resulting in increased morbidity. We aimed to evaluate factors associated with nonindex readmission and evaluate association of nonindex hospital readmission on outcomes in patients with ruptured aneurysm. Methods Readmissions within 90 days after aSAH treatment were identified in the 2010–2014 Nationwide Readmissions Database. Multivariable logistic regression identified patient and hospital characteristics associated with nonindex readmission. Separate multivariable models determined increased morbidity or risk of second readmission for nonindex readmissions. Results A total of 9254 patients who underwent treatment of ruptured aneurysms from 2010 to 2014 were identified. Of these, 1985 (21.5%) were readmitted within 90 days. Three hundred and fifty-five of these readmissions (17.9%) occurred to nonindex hospitals. Patients that were discharged to a skilled nursing or other facility (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.27–2.28]) had higher odds of nonindex readmission, whereas patients with private insurance were associated with lower odds of nonindex readmission (OR, 0.65; 95% CI, 0.46–0.92). Patients readmitted to a nonindex (vs. index) hospital were associated with increased likelihood of major complications (OR, 1.71; 95% CI, 1.18–2.48) and second readmissions (OR, 1.51; 95% CI, 1.17–1.96). Conclusions After treatment of a ruptured cerebral aneurysm, 17.9% of readmissions occurred at a nonindex hospital. These patients were at increased risk for major complications or subsequent readmissions, which may be because of care fragmentation. Interventions aimed at improving continuity of care may reduce higher morbidity associated with nonindex readmission.

The patient is a 54-year-old male, previously healthy, who was referred for chronic rhinosinusitis. He was previously treated by his primary care physician with intranasal steroids and antibiotics. He continued to complain of nasal congestion and cheek tenderness. A computed tomography (CT) scan was obtained that showed a unilateral left maxillary sinus mass with no bony erosion. On presentation, the patient was noted to have a unilateral mass protruding from the middle meatus. An in-clinic biopsy was consistent with sinonasal papilloma – inverted type (IP).

ObjectiveTo explore the association between cardiometabolic dysregulation, an integral component of allostatic load, and health risk behaviours (HRBs) of the Hong Kong healthy adult population.DesignSecondary analysis of cross-sectional anonymous data.SettingData on sociodemographics, self-reported health status, HRBs and biomarkers were extracted from the Hong Kong Population Health Survey 2014/2015.ParticipantsOne thousand five hundred and fifty-one participants aged 18–64 years without self-reported diagnoses of hypertension, diabetes mellitus, hyperlipidaemia, cardiovascular disease, cognitive impairment or cancer.Primary outcome measuresCardiometabolic dysregulation index (CMDI), ranging from 0 to 6, was calculated by counting the number of biomarkers including systolic blood pressure, diastolic blood pressure, waist to hip ratio, glycated haemoglobin, total cholesterol to high-density lipoprotein cholesterol ratio, and triglycerides that were above the respective normal level suggested by international guidelines and literature. HRBs including smoking, dietary habits and sleeping hours were collected by self-report questionnaire. Alcohol consumption was assessed by the 10-item Alcohol Use Disorders Identification Test, while physical activity level was measured using the Global Physical Activity Questionnaire. A composite HRB score, ranging from 0 to 5, was calculated as the cumulative number of HRBs. The effect of HRB on CMDI was evaluated by negative binomial regression with adjustment for socioeconomic status, health awareness and comorbidities of the participants.ResultsThe mean CMDI of the studied population was 1.6; 29.5% had a CMDI of 0, whereas 1.5% had a CMDI of 6. Significant difference was observed in mean CMDI between gender and different age groups. Sleeping less than 6 hours (incidence rate ratio (IRR)=1.26, pConclusionSmoking, physical inactivity and inadequate sleep—an essential yet often overlooked health behaviour—were associated with higher CMDI in the Hong Kong healthy adult population.

Unintentional injuries are major causes of mortality and morbidity. Although generally perceived as accidents, it is possible to identify those at higher risk and implement appropriate prevention measures. This study aims to investigate the common causes of unintentional injuries and their associated risk factors among a large representative sample. Data of 12,022 individuals who completed the Hong Kong Population Health Survey 2014/15 were extracted. The primary outcome was the prevalence of having unintentional injury(-ies) in the previous 12 months that was severe enough to limit daily activities. Multivariable logistic regression analyses were conducted to identify associations between injuries and sociodemographic, clinical and lifestyle factors. 14.5% of respondents reported episode(s) of unintentional injury in the past 12 months in the population level. The main causes of top three most severe unintentional injuries were sprains (24.0%), falls (19.9%) and being hit/struck (19.6%). 13.2% injury episodes were work-related among the most severe episode. Factors independently associated with significantly higher risks of injury included currently employed, homemaker or student, born in Hong Kong (as compared with immigrants), doctor-diagnosed chronic conditions, harmful alcohol consumption, insufficient sleep, and disturbed sleep. To summarize, unintentional injuries are highly prevalent and associated with harmful drinking, insufficient sleep, and disturbed sleep, which are potential modifiable risk factors for prevention.

Background The long-term outcomes of first-line choice among anti-thyroid drug (ATD), radioactive iodine (RAI) and thyroidectomy for Graves' disease (GD) patients remain unclear. Objective To compare the long-term morbidity, mortality, relapse, and costs of GD patients receiving first-line treatment. Methods A population-based retrospective cohort of GD patients initiating first-line treatment with ATD, RAI, or thyroidectomy as a first-line primary treatment between 2006 and 2018 from Hong Kong Hospital Authority was analyzed. Risks of all-cause mortality, cardiovascular diseases (CVD), atrial fibrillation (AF), psychological disease, diabetes, and hypertension were estimated using Cox proportional hazards regression models. The 10-year healthcare costs, change of comorbidities, and risk of relapse were compared across treatments. Results Over a median follow-up of 90 months with 47,470 person-years, 6385 patients (ATD, 74.93%; RAI, 19.95%; thyroidectomy, 5.12%) who received first-line treatment for GD were analyzed. Compared with ATD group, patients who had undergone surgery had significantly lower risks of all-cause mortality (HR = 0.363, 95%CI = 0.332-0.396), CVD (HR = 0.216, 95%CI = 0.195-0.239), AF (HR = 0.103, 95%CI = 0.085-0.124), psychological disease (HR = 0.279, 95%CI = 0.258-0.301), diabetes (HR = 0.341, 95%CI = 0.305-0.381) and hypertension (HR = 0.673, 95%CI = 0.632-0.718). Meanwhile, RAI group was also associated with decreased risks of all-cause mortality (HR = 0.931, 95%CI = 0.882-0.982), CVD (HR = 0.784, 95%CI = 0.742-0.828), AF (HR = 0.622, 95%CI = 0.578-0.67) and psychological disease (HR = 0.895, 95%CI = 0.855-0.937). The relapse rate was 2.41% in surgery, 75.60% in ATD, and 19.53% in RAI group. The surgery group was observed with a significant lower CCI score than the other two groups at the tenth-year follow-up. The mean 10-year cumulative healthcare costs in ATD, RAI, and surgery group was US$23915, US$24260, and US$20202, respectively. Conclusions GD patients who received surgery as an initial treatment appeared to have lower chances of all-cause mortality, CVD, AF, psychological disease, diabetes and hypertension in the long-term when compared to those treated with ATD or RAI. The surgery group had the lowest relapse and direct healthcare costs among the three treatment modalities. This long-term cohort study suggested surgery may have a larger role to play as an initial treatment for GD patients.

INTRODUCTION: The hippocampus is thought to be involved in movement, but its precise role in movement execution and inhibition has not been well studied. Previous work with direct neural recordings has found beta-band (13–30 Hz) modulation in both movement execution and inhibition throughout the motor system, but the role of beta-band modulation in the hippocampus during movement inhibition is not well understood. Here we perform a Go/No-Go reaching task in ten patients with medically-refractory epilepsy to study human hippocampal beta-power changes during movement. MATERIALS AND METHODS: Ten epilepsy patients (5 female; ages 21–46) were implanted with intracranial depth electrodes for seizure monitoring and localization. Local field potentials were sampled at 2000 Hz during a Go/No-Go movement task. Comparison of beta band power between Go and No-Go conditions was conducted using Wilcoxon signed-rank hypothesis testing for each patient. Sub-analyses were conducted to assess differences in the anterior versus posterior contacts, ipsilateral versus contralateral contacts, and male versus female beta power values. RESULTS: Eight out of ten patients showed significant beta power decreases during the Go movement response (p < 0.05) compared to baseline. Eight out of ten patients also showed significant beta power increases in the No-Go condition, occurring in the absence of movement. No significant differences were noted between ipsilateral versus contralateral contacts, nor in anterior versus posterior hippocampal contacts. Female participants had a higher task success rate than males and had significantly greater beta-power increases in the No-Go condition (p < 0.001). CONCLUSION: These findings indicate that increases in hippocampal beta power are associated with movement inhibition. To our knowledge, this study is the first to report this phenomenon in the human hippocampus. The beta band may represent a state-change signal involved in motor processing. Future focus on the beta band in understanding human motor and impulse control will be vital.

IntroductionPost-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects. We sought to exploit this phenomenon as a potential treatment for PTSD with a clinical trial of patients with PTSD receiving ECT.MethodsTwenty-eight participants with severe depression with comorbid PTSD referred for ECT treatment were randomly assigned to reactivation of a traumatic or non-traumatic memory using script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Assessments were completed by blinded raters. Secondary outcomes included a comparison of the change in heart rate while listening to the script.ResultsTwenty-five patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time.ConclusionsIn this RCT, ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT alone. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression.ClinicalTrials.govhttps://clinicaltrials.gov/ct2/show/NCT04027452Identifier: NCT04027452

Summary Introduction This study evaluates COVID-19 related patient risk, when undergoing management within one of the largest specialist centres in Europe, which rapidly implemented national COVID-19 safety guidelines. Method A prospective cohort study was undertaken in all patients who underwent surgical (n = 1429) or non-operative (n = 191) management during the UK COVID-19 pandemic peak (April–May 2020); all were evaluated for 30-day COVID-19 related death. A representative sample of elective/trauma/burns patients (surgery group, n = 729) were selected and also sub-analysed within a controlled cohort study design. Comparison was made to a random selection of non-operatively managed (non-operative group, n = 100) or waiting list (control group, n = 250) patients. These groups were prospectively followed-up and telephoned from the end of June (control group) or at 30 days post-first assessment (non-operative group)/post-operatively (surgery group). Results Complex general (9.2%, 136/1483) or regional (5.0%, 74/1483) anaesthesia cases represented 14.2% (210/1483) of operations undertaken. There were no 30-day post-operative (0/1429)/first assessment (0/191) COVID-19 related deaths. Neither the three sub-speciality plastic surgery, or non-operative groups, displayed increases in post-operative/first assessment symptoms in comparison to each other, or to control. The proportion of COVID-19 positive tests were: 7.1% (1/14) (non-operative), 5.9% (2/34) (burns) and 3.0% (3/99) (trauma); there were however no significant differences between these groups, the elective (0%, 0/54) and control (0%, 0/24) groups (p = 0.236). Conclusion We demonstrate that even heterogeneous sub-speciality patient groups, who required operative/non-operative management, did not incur an increased COVID-19 risk compared to each other or to control. These highly encouraging results were achieved with described, rapidly implemented service changes that were tailored to protect each patient group and staff.

Background Coronavirus disease (COVID-19) is a worldwide epidemic, and various countries have responded with different containment measures to reduce disease transmission, including stay-at-home orders, curfews, and lockdowns. Comparative studies have not yet been conducted to investigate the impact of these containment measures; these studies are needed to facilitate public health policy-making across countries. Objective The aim of this study was to describe and evaluate the impact of national containment measures and policies (stay-at-home orders, curfews, and lockdowns) on decelerating the increase in daily new cases of COVID-19 in 54 countries and 4 epicenters of the pandemic in different jurisdictions worldwide. Methods We reviewed the effective dates of the national containment measures (stay-at-home order, curfew, or lockdown) of 54 countries and 4 epicenters of the COVID-19 pandemic (Wuhan, New York State, Lombardy, and Madrid), and we searched cumulative numbers of confirmed COVID-19 cases and daily new cases provided by health authorities. Data were drawn from an open, crowdsourced, daily-updated COVID-19 data set provided by Our World in Data. We examined the trends in the percent increase in daily new cases from 7 days before to 30 days after the dates on which containment measures went into effect by continent, World Bank income classification, type of containment measures, effective date of containment measures, and number of confirmed cases on the effective date of the containment measures. Results We included 122,366 patients with confirmed COVID-19 infection from 54 countries and 24,071 patients from 4 epicenters on the effective dates on which stay-at-home orders, curfews, or lockdowns were implemented between January 23 and April 11, 2020. Stay-at-home, curfew, and lockdown measures commonly commenced in countries with approximately 30%, 20%, or 10% increases in daily new cases. All three measures were found to lower the percent increase in daily new cases to Conclusions Different national containment measures were associated with a decrease in daily new cases of confirmed COVID-19 infection. Stay-at-home orders, curfews, and lockdowns curbed the percent increase in daily new cases to

Chemo-resistant breast cancer is a major barrier to curative treatment for a significant number of women with breast cancer. Neoadjuvant chemotherapy (NACT) is standard first- line treatment for most women diagnosed with high-risk TNBC, HER2+, and locally advanced ER+ breast cancer. Current clinical prognostic tools evaluate four clinicopathological factors: Tumor size, LN status, pathological stage, and tumor molecular subtype. However, many similarly treated patients with identical residual cancer burden (RCB) following NACT experience distinctly different tumor relapse rates, clinical outcomes and survival. This problem is particularly apparent for incomplete responders with a high-risk RCB classification following NACT. Therefore, there is a pressing need to identify new prognostic and predictive biomarkers, and develop novel curative therapies to augment current standard of care (SOC) treatment regimens to save more lives. Here, we will discuss these unmet needs and clinical challenges that stand in the way of precision medicine and personalized cancer therapy.

Swallowing disorder is a health burden for the elderly in China. This study aimed to investigate the prevalence of dysphagia and to test the association between skeletal muscle strength and swallowing problems among community-dwelling older adults. A cross-sectional study. Community-dwelling Chinese elderly in China. 3361 adults aged 65 years or above were involved, among which 1740 (51.8%) were female, with average age of 72.64 (Standard deviation, SD=6.10) years old. Handgrip strength (HGS) was used to evaluate skeletal muscle strength. Dysphagia assessment was performed using the Eating Assessment Tool-10 (EAT-10) and the 30mL water swallow test (WST). Binary logistic regression was used to evaluate the relationship between skeletal muscle strength and dysphagia, and covariates as age, gender, material status, etc. were adjusted. The prevalence of dysphagia were 5.5% and 12.9%, screened by EAT-10 and 30mL WST respectively. Participants with dysphagia showed lower HGS (21.73 ± 9.20 vs. 25.66 ± 11.32, p

There is an urgent need for new therapeutic strategies to contain the spread of the novel coronavirus disease 2019 (COVID-19) and to curtail its most severe complications. Severely ill patients experience pathologic manifestations of acute respiratory distress syndrome (ARDS), and clinical reports demonstrate striking neutrophilia, elevated levels of multiple cytokines, and an exaggerated inflammatory response in fatal COVID-19. Mechanical respirator devices are the most widely applied therapy for ARDS in COVID-19, yet mechanical ventilation achieves strikingly poor survival. Many patients, who recover, experience impaired cognition or physical disability. In this review, we argue the need to develop therapies aimed at inhibiting neutrophil recruitment, activation, degranulation, and neutrophil extracellular trap (NET) release. Moreover, we suggest that currently available pharmacologic approaches should be tested as treatments for ARDS in COVID-19. In our view, targeting host-mediated immunopathology holds promise to alleviate progressive pathologic complications of ARDS and reduce morbidities and mortalities in severely ill patients with COVID-19.

Objectives: The Institute for Clinical and Economic Review (ICER) publishes reports on the clinical and economic value of drugs for US payers. Each report is subject to a public meeting by one of three independent expert committees (the California Technology Assessment Forum [CTAF], Midwest Comparative Effectiveness Public Advisory Council [CEPAC], and New England CEPAC) discusses the report and votes on the evidence presented. This research compares and contrasts outcomes by committee. Methods: All publicly available final ICER reports of pharmaceuticals (01/01/2014-12/31/2019) were screened and key data extracted. Results: 38 ICER reports of pharmaceuticals were identified (CTAF: 11; Midwest CEPAC: 12; New England CEPAC: 15), encompassing 110 drugs in 78 conditions/subgroups. Clinical ratings were provided for 277 drug comparisons (CTAF: 41; Midwest CEPAC: 46; New England CEPAC: 190). For the CTAF, Midwest CEPAC, New England CEPAC, respectively, 19 (46%), 23 (50%), and 33 (17%) drug comparisons achieved a rating of A, B, or B+; 3 (7%), 9 (20%), and 80 (42%) achieved a rating of C, C+, C-, or D; 19 (46%), 14 (30%), and 77 (41%) achieved a rating of P/I or I. Cost-utility assessments were undertaken for 117 treatment settings (CTAF: 35; Midwest CEPAC: 32; New England CEPAC: 50). At a willingness-to-pay threshold of $150,000/QALY, 11 therapies (31%) were deemed cost-effective/cost-saving by the CTAF, 9 (28%) by the Midwest CEPAC, and 21 (42%) by the New England CEPAC. Of the 51 votes for healthcare value, most drugs had a majority vote of low or intermediate value: CTAF: 9 (90%); Midwest CEPAC: 12 (86%); New England CEPAC: 22 (81%). Conclusions: There are generally few differences between ICER committee outcomes, although there are some variances, which are likely due to therapy area focus. Considering healthcare value, ICER committees are generally consistent in reporting that most drugs provide low to intermediate value.

Background Venous thromboembolism (VTE) is a common, high-mortality condition among surgical cancer patients. Comprehensive analyses of VTE among postoperative cancer patients are lacking. We sought to determine the association between readmission with VTE and primary cancer diagnosis in a nationwide database at 90- and 180-days after initial admission for cancer surgery. Methods Retrospective analyses of post-surgical cancer patients readmitted with VTE were conducted using data from the Nationwide Readmissions Database (NRD) (2010–2014). Multivariate logistic regression models adjusting for patient and hospital factors were used to determine 90- and 180-day readmission rates for VTE by cancer type. Patient factors associated with readmission were also examined. Results Among a sample of 535,992 cancer patients undergoing tumor resection, readmission with VTE occurred in 1.7% within 90-days and 2.3% within 180-days. Patients readmitted for VTE experienced a 7% mortality rate. Highest rates of VTE readmission at 180 days occurred in brain (6.7%), pancreatic (5.6%), and respiratory and intrathoracic cancers (4.4%). Using pancreatic cancer as reference, brain cancer had the highest odds of readmission at 180-days (OR 2.23, 95% CI [1.95–2.55]). Conclusion Readmission with VTE among surgical cancer patients occurred in 2.3% of patients within 180 days. Among cancer types, primary brain cancer was independently associated with readmission with VTE.

Clinical outcomes in the surgical management of severe traumatic brain injury (TBI) have been shown to vary across different hospital institutions. The effect of the safety-net burden on postoperative mortality, complication rates, and failure to rescue rates is unclear. We evaluated the relationship of the safety-net burden with outcomes in the treatment of patients with severe TBI undergoing neurosurgery.The hospitals were grouped according to their safety-net burden, defined as the proportion of Medicaid and uninsured patient charges for all hospitalizations during that time. Multivariate analyses were performed to examine significant associations with the degree of safety-net burden while controlling for potential confounders.Data from 20,989 encounters in 788 hospitals were included. Compared with low-burden hospitals (LBHs), high-burden hospitals (HBHs; odds ratio [OR], 1.48; 95% confidence interval [CI], 1.04-2.12; P = 0.03) had greater mortality rates. Major complications were more likely to occur at HBHs (OR, 1.44; 95% CI, 1.12-1.84; P0.01) compared with LBHs. The failure to rescue rates were similar among all safety-net burden hospital groups. Patients at HBHs also had an increased likelihood of an extended length of stay (OR, 1.92; 95% CI, 1.12-3.29; P = 0.02) and receiving a tracheostomy or gastrostomy (OR, 1.99; 95% CI, 1.36-2.89; P0.01) compared with patients at LBHs.The present study found that a greater hospital safety-net burden was independently associated with greater rates of mortality and major complications in the treatment of patients with severe TBI undergoing neurosurgery. Further research in evaluating the cause of disparities in mortality outcomes at high safety-burden hospitals is needed.

When individuals are on probation, they face challenges with securing employment and safe housing due to their criminal records, which may make food access problematic. Food insecurity is a construct used as a marker for food access that considers financial constraints and has been associated with poorer health and substance use. There is limited research on the extent of food insecurity and associated morbidities and substance use among adults on probation. We conducted a cross-sectional study in 2016, surveying 304 probationers in Rhode Island to determine whether food insecurity is associated with obesity, high blood pressure, depression, and substance use. Separate logistic regression models were used to determine the associations between food insecurity and obesity, high blood pressure, depression, and substance use. Food insecurity was experienced by 70% of our study population. The estimated prevalence of high blood pressure was significantly higher in our study sample compared to the general US population. Food insecurity was not associated with obesity, high blood pressure, or current drug use in this study sample. Food insecurity was independently associated with more than three times greater odds of being depressed (AOR 3.33, 95%CI 1.89, 5.86) and a nearly twofold greater odds of self-reporting a lower health status (AOR 1.91, 95%CI 1.18, 3.10) after adjusting for gender, race/ethnicity, age, income categories, and being homeless. Probationers were found to have a higher estimated prevalence of high blood pressure and food insecurity compared to the general population, which highlights the health disparities faced by this population. Our findings have important implications for future research and interventions to decrease the health burden not only on the individuals but their families and communities.

Background: Olaparib (Lynparza®) is a PARP inhibitor that alters the repair of single-strand DNA breaks. Durvalumab (Imfinzi®) is a monoclonal antibody against programmed cell death ligand 1 (anti-PD-L1) that promotes antitumor immune responses. MEDIOLA (NCT02734004) is a Ph I/II open-label, multicenter study enrolling patients (pts) across several tumor types (small-cell lung cancer, gastric cancer, germline BRCA-mutated [gBRCAm] BC, or platinum sensitive relapsed gBRCAm ovarian cancer). 34 pts with gBRCAm BC received olaparib 300 mg po bid for a 4-wk run-in, followed by olaparib 300 mg po bid and durvalumab 1.5 g IV q4 wks. Encouraging preliminary results support an expansion cohort in a BRCAm popn. Evidence suggests that mutations in other homologous recombination repair (HRR) genes may confer a BRCA-like phenotype, warranting an expansion of the study population beyond BRCAm. Inhibition of vascular endothelial growth factor (VEGF) has been reported to enhance the efficacy of chemotherapy in TNBC. In addition, VEGF inhibition potentiates PARP inhibitor activity, particularly in pts who do not carry BRCAm. Combinations of immune checkpoint inhibitors and bevacizumab, an anti-VEGF-A antibody, have shown promising results in other tumor types. Thus, MEDIOLA will additionally explore the efficacy and safety of olaparib + durvalumab in combination with bevacizumab in TNBC pts. Trial design: Pts in the additional MBC cohorts will receive combination olaparib and durvalumab with no olaparib run-in. Pts in the TNBC cohort will also receive concurrent bevacizumab 10 mg/kg q 2 wks. Tumor assessments will be performed at baseline and every 8 wks thereafter. Eligibility criteria: Pts with histologically confirmed, locally advanced or metastatic HER2-neg BC, who are PARP-inhibitor and immunotherapy naïve. Prior anthracycline and/or taxane therapy in early or MBC is required. Prior platinum therapy is allowed, if there was no disease progression while receiving treatment and at least 12 mths has elapsed since the last dose. Pts will undergo BRCA and HRR mutation testing and will be assigned to a cohort based on their mutation status, as illustrated in Table 1. Specific aims: Cohort-specific primary efficacy endpoint targets were calculated aiming for superiority to standard of care treatment (Table 1). Other primary outcomes are safety and tolerability. Secondary endpoints are PK, DCR at 24 wks, objective response rate, duration of response, progression-free survival and overall survival. Exploratory endpoints include the analysis of tumor-infiltrating lymphocytes and PD-L1 expression. Statistical methods: The expansion cohort will have a single-stage statistical design. Bayesian predictive probability design will be used for the analysis of the HRRm and TNBC triplet cohorts. Accrual: Accrual targets are shown in Table 1. First subject will be enrolled in Nov 2018. New MEDIOLA BC cohortsCohort nameTarget accrualDrugsPopnPrimary endpointBreast BRCAm expansion80Olap+DurvHER2-neg, tBRCAmORR 70%Breast HRRm cohort29Olap+DurvHER2-neg, non BRCAm, HRRm-posDCR at 16 wks 80%TNBC triplet cohort30Olap+Durv+BevTNBC, non BRCAm, non HRRmDCR at 16 wks 80%Bev, bevacizumab; durv, durvalumab; olap, olaparib Citation Format: Domchek SM, Postel-Vinay S, Im S-A, Hee Park Y, Delord J-P, Italiano A, Alexandre J, You B, Bastian S, Krebs MG, Waqar S, Lanasa M, Angell HK, Tang M, Gresty C, Opincar L, Herbolsheimer P, Kaufman B. MEDIOLA: An open-label, phase I/II basket study of olaparib (PARP inhibitor) and durvalumab (anti-PD-L1 antibody)–Additional breast cancer cohorts [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-05-03.

Aims To compare cardio-renal outcomes and incurred direct medical costs of patients initiating sodium glucose cotransporter-2 inhibitors (SGLT2i) versus glucagon-like peptide-1 receptor agonists (GLP-1RA). Methods A population-based cohort of patients with type 2 diabetes was identified from Hong Kong Hospital Authority. Patients who were free from cardiovascular and end-stage renal diseases at baseline, and newly treated with SGLT2i (n = 2,541) or GLP-1RA (n = 303), were included. Risks of developing cardio-renal complications, incurred direct medical costs, and changes in clinical parameters were assessed between groups. Results Over a median follow-up of 12.5 months in SGLT2i group and 25.5 months in GLP-1RA group, SGLT2i users were associated with significantly lower risk of heart failure compared with those on GLP-1RA [hazard ratio = 0.183, 95 %CI = (0.045, 0.745)]. 1-year change in clinical parameters also favored use of SGLT2i over GLP-1RA, where the former was associated with a larger reduction in fasting glucose level [difference-in-difference = −0.87 mmol/L, 95 %CI = (−1.42, −0.33), p = 0.002]. The two groups had comparable direct medical costs after 1-year of follow-up. Conclusion Patients initiating SGLT2i experienced a significantly lower risk of heart failure than those on GLP-1RA, alongside better glycemic control through a larger reduction in fasting glucose level over one-year follow-up, while direct medical cost incurred was comparable to that of GLP-1RA.

Objective This study aims to investigate the clinical effects of benzodiazepines or anticonvulsant use during a course of electroconvulsive therapy (ECT). Method A case report study of a patient who received ECT with and without concomitant flurazepam and pregabalin is presented. The literature on the use of benzodiazepines and anticonvulsants during ECT is reviewed. Results A woman with treatment resistant depression received a course of ECT while taking flurazepam and pregabalin, but seizures were of short duration and symptomatic improvement was minimal. After discontinuation of flurazepam and pregabalin, a course of right unilateral ultrabrief ECT was associated with adequate seizures and remission of depression and suicidal ideation. Our literature review suggests that benzodiazepines decrease seizure duration, but most evidence shows no association with increased seizure threshold. One prospective RCT and 3 large retrospective studies found that benzodiazepines compromise the efficacy of unilateral but not bilateral ECT. Regarding anticonvulsants, several studies had varied and contradictory results on their effect on seizure duration and seizure threshold. Of the 2 large retrospective studies and 3 RCTs, only 1 retrospective study showed that anticonvulsants decrease the efficacy of ECT. Conclusions Judicious assessment of all medications used in combination with ECT is recommended. Overall, published studies suggest that benzodiazepines and anticonvulsants impact the clinical outcomes of ECT less than what would be expected given their pharmacologic effects. However, there are significant gaps in the literature, including a lack of study on suprathreshold stimulation of right unilateral ECT and the possibility of a greater effect with higher medication doses.

The tumour necrosis factor-α (TNF-α) promoter -308 A/G polymorphism plays an important role in the aetiology of systemic lupus erythematosus (SLE). Several studies have estimated the association between TNF-α -308 A/G and SLE risk. However, results were inconsistent. A case-control study was carried out to explore the association between TNF-α -308 A/G and the SLE risk in a Chinese Han population. Meta-analysis combining present with previous studies was conducted to further explore the association. Our case-control study included 556 patients with SLE along with 570 matched healthy controls. TNF-α -308 A allele was significantly increased in patients with SLE compared with controls (OR = 2.184, 95% CI: 1.718-2.778, P

Background There is growing interest in the potential of neuromodulation options in treatment-resistant obsessive-compulsive disorder (OCD). Magnetic seizure therapy (MST), is a new treatment intervention in which generalized seizures are induced with transcranial magnetic stimulation. We conducted a pilot study to assess the efficacy and cognitive effects of MST in patients with treatment-resistant OCD. Methods In an open-label pilot study, participants with treatment-resistant OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores of ≥16 were treated with up to 24 acute treatments. The primary clinical outcomes were clinical response (Y-BOCS score reduction ≥30%) and remission (final Y-BOCS score ≤8). A neurocognitive battery, the Quick Inventory for Depressive Symptoms-Self Report (QIDS-SR), the Beck Scale for Suicidal Ideation (SSI), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were also completed as secondary measures. Results Ten participants with OCD who had not responded to medications or psychotherapy enrolled in the study and seven completed an adequate trial (defined as ≥8 treatments). MST was associated with minimal cognitive effects except for some decrease in autobiographical memory and no serious adverse effects. Only one participant met the predefined criteria for response, and none for remission. The baseline and endpoint Y-BOCS scores were not statistically different. Conclusion Overall, MST was not beneficial in a small group of patients with treatment-resistant OCD. At this time, other studies of MST for OCD are not warranted until different coil placements targeting other brain circuits can be proposed.

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration NCT01596608; clinicaltrials.gov

Background: The risks of all-cause mortality, cardiovascular diseases (CVD), end-stage renal diseases (ESRD), and severe hypoglycaemia (SH) among obese patients with T2DM initiating novel glucose-lowering medications (SGLT2i and GLP-1RA) and those undergoing bariatric surgery were unknown. Methods: This was a population-wide retrospective cohort study. Data were collected from the Hong Kong Hospital Authority database from 2006 to 2017. Generalized matching weights of propensity score was applied to balance out baseline covariates of obese patients with T2DM who underwent bariatric surgery, or initiated SGLT2i or GLP-1RA. Hazard ratios (HRs) for CVD, ESRD, and mortality from any causes were assessed among three groups using Cox proportional hazard models. Findings: Over a median follow-up period of 14 months with 2916·25 person-years, incidence of CVD was the highest in SGLT2i group (7·156/100 person-years). Incidences of ESRD and all-cause mortality were the highest in bariatric surgery group (0·453 and 2·316/100 person-years). SGLT2i users had not significantly lower risk of all-cause mortality (HR=0·343, 95%CI=0·089-1·326, p=0·121), CVD (HR=1·125, 95%CI=0·576-2·198, p=0·729), ESRD (HR=0·480, 95%CI=0·109-2·107, p=0·331) and SH (HR=2·654, 95%CI=0·713-9·871, p=0·145) than bariatric surgery candidates. When comparing with bariatric surgery, GLP-1RA was not associated with significant reduction in risks of all-cause mortality (HR=0·350, 95%CI=0·117-1·045, p=0·060), CVD (HR=0·722, 95%CI=0·327-1·596, p=0·421), ESRD (0·251, 95%CI=0·034-1·836, p=0·173) and SH (1·923, 95%CI=0·418-8·853, p=0·401) events. Patients undergoing bariatric surgery had significantly greater improvement in BMI (-6·879kg/m2 , -0·787kg/m2 , -1·160kg/m2 , p

Objective: To conduct a systematic review and meta-analysis on the comorbidities, symptoms, clinical characteristics and treatment of COVID-19 patients.Method: Epidemiological studies published in 2020 (from January-March) on the clinical presentation, laboratory findings and treatments of COVID-19 patients were identified from PubMed/MEDLINE and Embase databases. Studies published in English by 27th March, 2020 with original data were included. A random-effects model was used to aggregate estimates across eligible studies and produce meta-analytic estimates. Primary outcomes included comorbidities of COVID-19 patients, their symptoms presented on hospital admission, laboratory results and radiological outcomes, and pharmacological and in-patient treatments.Results: 77 studies were included in this meta-analysis, accounting for a total of 11,028 COVID- 19 patients in multiple countries. The most common comorbidities were hypertension (18.1%, 95%CI: 15.4-20.8%). The most frequently identified symptoms were fever (72.4%, 95%CI: 67.2-77.7%) and cough (55.5%, 95%CI: 50.7-60.3%). For pharmacological treatment, 63.9% (95%CI: 52.5-75.3%), 62.4% (95%CI: 47.9-76.8%) and 29.7% (95%CI: 21.8-37.6%) of patients were given antibiotics, antiviral, and corticosteroid, respectively. Notably, 62.6% (95%CI: 39.9- 85.4%) and 20.2% (95%CI: 14.6-25.9%) of in-patients received oxygen therapy and non- invasive mechanical ventilation, respectively.Conclusions: This meta-analysis informed healthcare providers about the timely status of characteristics and treatments of COVID-19 patients across different countries.PROSPERO Registration Number: CRD42020176589

Background and objective Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment. Methods A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs5Hz ) and reactance (Xrs5Hz ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion-convection-dependent (Sacin) and convection-dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily. Results Treatment improved ACQ5 (P = 0.0002), FEV1 (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs5Hz (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs5Hz (rs = 0.52, P = 0.03) and Rrs5Hz (rs = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs5Hz (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC-AUC = 0.91, P = 0.007). Conclusion Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs5Hz and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up-titration in uncontrolled asthmatic patients.

Alcohol is the most widely abused substance in Namibia and is associated with poor adherence and retention in care among people on antiretroviral therapy (ART). Electronic screening and brief interventions (eSBI) are effective in reducing alcohol consumption in various contexts. We used a mixed methods approach to develop, implement, and evaluate the introduction of an eSBI in two ART clinics in Namibia. Of the 787 participants, 45% reported some alcohol use in the past 12 months and 25% reported hazardous drinking levels. Hazardous drinkers were more likely to be male, separated/widowed/divorced, have a monthly household income > $1000 NAD, and report less than excellent ART adherence. Based on qualitative feedback from participants and providers, ART patients using the eSBI for the first time found it to be a positive and beneficial experience. However, we identified several programmatic considerations that could improve the experience and yield in future implementation studies.

Acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) are rare pustular skin disorders with systemic involvement. IL-17A/F is a proinflammatory cytokine involved in various neutrophilic inflammatory disorders. Here we show that IL-17A/F is highly expressed by innate immune cells such as neutrophils and mast cells in both AGEP and GPP.

Fueled by the burgeoning opioid epidemic, valve surgeries for substance use disorder-related infective endocarditis (SUD-IE) are increasing. The impact of substance use disorder on postvalve replacement morbidity needs further investigation.We queried The Society of Thoracic Surgeons Adult Cardiac Surgery Database for all valve surgeries for infective endocarditis at Tufts Medical Center (2002-2016) and collected demographic and disease-related data, including timing of mortality subclassified as short-term (6 months including operative), midterm (6 months to 5 years), and extended-term (5 years). Patients with documentation of illicit drug use before the operation were considered to have SUD-IE. Deaths were confirmed through review of medical record and matching with the Massachusetts Vital Statistics Database. We performed univariate and multivariate proportional hazard regressions examining the impact of substance use disorder mortality in people who received a valve replacement.In the cohort of 228 patients, 80 (35%) had SUD-IE. Eight-six people (38%) died, and overall mortality was higher in people with SUD-IE compared with non-SUD-IE (48% vs 32%, P = .025). SUD-IE was associated with a higher risk of overall mortality (adjusted hazard ratio, 2.41; 95% confidence interval, 1.38-4.20; P = .002). Although the difference between short-term or extended-term mortality was not significant, SUD-IE was associated with increased frequency of midterm mortality (53% vs 31%, P = .003).Our data reflect high rates of postvalve surgery morbidity and mortality in people with SUD-IE at a tertiary care center. The midterm postoperative period is a vulnerable period for people with SUD-IE worthy of further investigation.

Aim Current guideline recommends insulin as fourth-line glucose-lowering medications. However, treatment effects of sodium glucose co-transporter-2 inhibitors (SGLT2i) on the risk of complications are uncertain. This study examines risks of all-cause mortality, cardiovascular diseases (CVD) and end-stage renal diseases (ESRD) in type 2 diabetes mellitus (T2DM) patients on triple oral glucose-lowering medications initiating SGLT2i, insulin or other oral medications. Methods A population-based retrospective cohort of patients with T2DM between 2006–2017 was extracted from Hong Kong Hospital Authority database. Patients who were initiated a fourth-line therapy with SGLT2i, insulin or other oral medications were included. Hazard ratios (HRs) for all-cause mortality, CVD and ESRD were assessed using Cox proportional hazard models. Results Over a median follow-up period of 18.5 months with 63,122 person-years, SGLT2i and insulin group had the lowest and highest incidence rate of all-cause mortality, CVD and ESRD (1.06, 0.65 and 0.61 vs 4.25, 5.58 and 4.39/100 person-years), respectively. Initiating SGLT2i as fourth-line medication had more benefits on CVD, in particular coronary heart disease and stroke. Insulin users had higher risks of CVD (HR = 8.04, 95%CI = 3.06–21.12) than SGLT2i users. SGLT2i was associated with insignificant reduction in ESRD (HR = 4.62, 95%CI = 0.73–29.09) and all-cause mortality (HR = 3.06, 95%CI = 0.75–12.45), and HF (HR = 2.99, 95%CI = 0.37–24.42) among patients without established HF. Conclusion Among T2DM patients initiating fourth-line therapy, SGLT2i users had significant benefits in lowering risk of CVD, and potential benefits in lowering risks of ESRD and all-cause mortality. SGLT2i was the preferred fourth-line glucose-lowering medication least likely to be associated with complication risks.

Background Metastatic breast cancer exhibits diverse and rapidly evolving intra- and inter-tumor heterogeneity. Patients with similar clinical presentations often display distinct tumor responses to standard of care (SOC) therapies. Genome landscape studies indicate that EGFR/HER2/RAS “pathway” activation is highly prevalent in malignant breast cancers. The identification of therapy-responsive and prognostic biomarkers is paramount important to stratify patients and guide therapies in clinical oncology and personalized medicine. Methods In this study, we analyzed matched pairs of tumor specimens collected from 182 patients who received neoadjuvant systemic therapies (NST). Statistical analyses were conducted to determine whether EGFR/HER2/RAS pathway biomarkers and clinicopathological predictors, alone and in combination, are prognostic in breast cancer. Findings SIAH and EGFR outperform ER, PR, HER2 and Ki67 as two logical, sensitive and prognostic biomarkers in metastatic breast cancer. We found that increased SIAH and EGFR expression correlated with advanced pathological stage and aggressive molecular subtypes. Both SIAH expression post-NST and NST-induced changes in EGFR expression in invasive mammary tumors are associated with tumor regression and increased survival, whereas ER, PR, and HER2 were not. These results suggest that SIAH and EGFR are two prognostic biomarkers in breast cancer with lymph node metastases. Interpretation The discovery of incorporating tumor heterogeneity-independent and growth-sensitive RAS pathway biomarkers, SIAH and EGFR, whose altered expression can be used to estimate therapeutic efficacy, detect emergence of resistant clones, forecast tumor regression, differentiate among partial responders, and predict patient survival in the neoadjuvant setting, has a clear clinical implication in personalizing breast cancer therapy. Funding This work was supported by the Dorothy G. Hoefer Foundation for Breast Cancer Research (A.H. Tang); Center for Innovative Technology (CIT)-Commonwealth Research Commercialization Fund (CRCF) (MF14S-009-LS to A.H. Tang), and National Cancer Institute (CA140550 to A.H. Tang)., Graphical abstract Image 1, Highlights • EGFR/RAS pathway activation is prevalent in breast cancer with poor prognosis. • The two RAS pathway biomarkers, SIAH and EGFR, are prognostic in breast cancer. • The RAS pathway biomarkers can be used to stratify patients and guide therapies. • The RAS pathway biomarkers can be used to identify resistant tumor clones post NST. • SIAH and EGFR outperform ER, PR, HER2 and Ki67 in predicting patient survival. The prognostic power of SIAH/EGFR is comparable to that of clinical predictors Early stage breast cancer is amenable to standard of care therapies with excellent long-tern survival. Locally advanced and metastatic breast cancer has a much worse prognosis despite intense systemic and locoregional therapies. This disparity in prognosis underlines the acute need to identify resistant breast cancer cells, and administer and select effective therapies to eradicate resistant mammary tumors. We report that the activation of the EGFR/RAS/SIAH pathway can be used to identify resistant tumor clones and differentiate effective from ineffective therapies, and therefore predict tumor relapse and patient survival in human breast cancer during first-line neoadjuvant systemic therapy in clinic.