Textbook outcome in patients with biliary duct injury during cholecystectomy.

BACKGROUND: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management. METHODS: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications. RESULTS: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001). CONCLUSION: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI.

Intraductal papillary neoplasm of the bile duct: The new frontier of biliary pathology.

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

Using the Comprehensive Complication Index to Rethink the ISGLS Criteria for Post-hepatectomy Liver Failure in an International Cohort of Major Hepatectomies.

OBJECTIVE: To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality. SUMMARY OF BACKGROUND DATA: PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. METHODS: Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. RESULTS: Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality. CONCLUSIONS: In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Indications, trends, and perioperative outcomes of minimally invasive and open liver surgery in non-obese and obese patients: An international multicentre propensity score matched retrospective cohort study of 9963 patients.

BACKGROUND: Despite the worldwide increase of both obesity and the use of minimally invasive liver surgery (MILS), evidence regarding the safety and eventual benefits of MILS in obese patients is scarce. The aim of this study was therefore to compare the outcomes of non-obese and obese patients (BMI 18.5-29.9 and BMI≥30, respectively) undergoing MILS and OLS, and to assess trends in MILS use among obese patients. METHODS: In this retrospective cohort study, patients operated at 20 hospitals in eight countries (2009-2019) were included and the characteristics and outcomes of non-obese and obese patients were compared. Thereafter, the outcomes of MILS and OLS were compared in both groups after propensity-score matching (PSM). Changes in the adoption of MILS during the study period were investigated. RESULTS: Overall, 9963 patients were included (MILS: n = 4687; OLS: n = 5276). Compared to non-obese patients (n = 7986), obese patients(n = 1977) were more often comorbid, less often received preoperative chemotherapy or had a history of previous hepatectomy, had longer operation durations and more intraoperative blood loss (IOBL), paralleling significantly higher rates of wound- and respiratory-related complications. After PSM, MILS, compared to OLS, was associated, among both non-obese and obese patients, with less IOBL (200 ml vs 320 ml, 200 ml vs 400 ml, respectively), lower rates of transfusions (6.6% vs 12.8%, 4.7% vs 14.7%), complications (26.1% vs 35%, 24.9% vs 34%), bile leaks(4% vs 7%, 1.8% vs 4.9%), liver failure (0.7% vs 2.3%, 0.2% vs 2.1%), and a shorter length of stay(5 vs 7 and 4 vs 7 days). A cautious implementation of MILS over time in obese patients (42.1%-53%, p < .001) was paralleled by stable severe morbidity (p = .433) and mortality (p = .423) rates, despite an accompanying gradual increase in surgical complexity. CONCLUSIONS: MILS is increasingly adopted and associated with perioperative benefits in both non-obese and obese patients.

Survival Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-2).

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan−Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p > 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p > 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach.

Indocyanine Green Fluorescence Navigation in Liver Surgery: A Systematic Review on Dose and Timing of Administration.

BACKGROUND: Indocyanine green (ICG) fluorescence has proven to be a high potential navigation tool during liver surgery; however, its optimal usage is still far from being standardized. METHODS: A systematic review was conducted on MEDLINE/PubMed for English articles that contained the information of dose and timing of ICG administration until February 2021. Successful rates of tumor detection and liver segmentation, as well as tumor/patient background and imaging settings were also reviewed. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Out of initial 311 articles, a total of 72 manuscripts were obtained. The quality assessment of the included studies revealed usually low; only 9 articles got qualified as high quality. Forty articles (55%) focused on open resections, whereas 32 articles (45%) on laparoscopic and robotic liver resections. Thirty-four articles (47%) described tumor detection ability, and 25 articles (35%) did liver segmentation ability, and the others (18%) did both abilities. Negative staining was reported (42%) more than positive staining (32%). For tumor detection, majority used the dose of 0.5 mg/kg within 14 days before the operation day, and an additional administration (0.02-0.5 mg/kg) in case of longer preoperative interval. Tumor detection rate was reported to be 87.4% (range, 43%-100%) with false positive rate reported to be 10.5% (range, 0%-31.3%). For negative staining method, the majority used 2.5 mg/body, ranging from 0.025 to 25 mg/body. For positive staining method, the majority used 0.25 mg/body, ranging from 0.025 to 12.5 mg/body. Successful segmentation rate was 88.0% (range, 53%-100%). CONCLUSION: The time point and dose of ICG administration strongly needs to be tailored case by case in daily practice, due to various tumor/patient backgrounds and imaging settings.

Incidence and Clinical Impact of Bile Leakage after Laparoscopic and Open Liver Resection: An International Multicenter Propensity Score-Matched Study of 13,379 Patients.

BACKGROUND: Despite many developments, postoperative bile leakage (POBL) remains a relatively common postoperative complication after laparoscopic liver resection (LLR) and open liver resection (OLR). This study aimed to assess the incidence and clinical impact of POBL in patients undergoing LLR and OLR in a large international multicenter cohort using a propensity score-matched analysis. STUDY DESIGN: Patients undergoing LLR or OLR for all indications between January 2000 and October 2019 were retrospectively analyzed using a large, international, multicenter liver database including data from 15 tertiary referral centers. Primary outcome was clinically relevant POBL (CR-POBL), defined as Grade B/C POBL. RESULTS: Overall, 13,379 patients met the inclusion criteria and were included in the analysis (6,369 LLR and 7,010 OLR), with 6.0% POBL. After propensity score matching, a total of 3,563 LLR patients were matched to 3,563 OLR patients. In both groups, propensity score matching accounted for similar extent and types of resections. The incidence of CR-POBL was significantly lower in patients after LLR as compared with patients after OLR (2.6% vs 6.0%; p < 0.001). Among the subgroup of patients with CR-POBL, patients after LLR experienced less severe (non-POBL) postoperative complications (10.1% vs 20.9%; p = 0.028), a shorter hospital stay (12.5 vs 17 days; p = 0.001), and a lower 90-day/in-hospital mortality (0% vs 5.4%; p = 0.027) as compared with patients after OLR with CR-POBL. CONCLUSION: Patients after LLR seem to experience a lower rate of CR-POBL as compared with the open approach. Our findings suggest that in patients after LLR, the clinical impact of CR-POBL is less than after OLR.

Development and external validation of a prediction model for overall survival after resection of distal cholangiocarcinoma.

BACKGROUND: Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model for 3-year OS after pancreatoduodenectomy for dCCA. METHODS: The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009-2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008-2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy). RESULTS: Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01-1.03), pT (HR 1.43, 95% CI 1.07-1.90) and pN category (pN1: HR 1.78, 95% CI 1.37-2.32; pN2: HR 2.21, 95% CI 1.63-3.01), resection margin status (HR 1.79, 95% CI 1.39-2.29) and tumour differentiation (HR 2.02, 95% CI 1.62-2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%). CONCLUSIONS: The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from Western European countries on their prognosis, and may be used to stratify patients for clinical trials.

Comparison of Mental Health Symptom Changes from pre-COVID-19 to COVID-19 by Sex or Gender: A Systematic Review and Meta-analysis

ImportanceWomen and gender-diverse individuals have faced disproportionate socioeconomic burden during COVID-19. There have been reports that this has translated into greater negative changes in mental health, but this has been based on cross-sectional research that has not accounted for pre-COVID-19 differences. ObjectiveTo compare mental health symptom changes since pre-COVID-19 by sex or gender. Data SourcesMEDLINE, PsycINFO, CINAHL, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, medRxiv, and Open Science Framework (December 31, 2019 to August 30, 2021). Study SelectionEligible studies compared mental health symptom changes from pre-COVID-19 to COVID-19 by sex or gender. Data Extraction and SynthesisData was extracted by a single reviewer with validation by a second reviewer. Adequacy of study methods and reporting was assessed using an adapted version of the Joanna Briggs Institute Checklist for Prevalence Studies. A restricted maximum-likelihood random-effects meta-analyses was conducted. Main Outcomes and MeasuresAnxiety symptoms, depression symptoms, general mental health, and stress measured continuously or dichotomously. Results12 studies (10 unique cohorts) were included. All compared females or women to males or men; none included gender-diverse individuals. Continuous symptom change differences were not statistically significant for depression (standardized mean difference [SMD]= 0.12, 95% CI -0.09 to 0.33; 4 studies, 4,475 participants; I2=69.0%) and stress (SMD= - 0.10, 95% CI -0.21 to 0.01; 4 studies, 1,533 participants; I2=0.0%), but anxiety (SMD= 0.15, 95% CI 0.07 to 0.22; 4 studies, 4,344 participants; I2=3.0%) and general mental health (SMD= 0.15, 95% CI 0.12 to 0.18; 3 studies, 15,692 participants; I2=0.0%) worsened more among females or women than males or men during COVID-19. There were no significant differences in changes in proportion above a cut-off: anxiety (difference= -0.05, 95% CI -0.20 to 0.11; 1 study, 217 participants), depression (difference= 0.12, 95% CI -0.03 to 0.28; 1 study, 217 participants), general mental health (difference= -0.03, 95% CI -0.09 to 0.04; 3 studies, 18,985 participants; I2=94.0%), stress (difference= 0.04, 95% CI -0.10 to 0.17; 1 study, 217 participants). Conclusion and RelevanceMental health outcomes did not differ or were worse by amounts below thresholds for clinical significance for women compared to men. RegistrationPROSPERO (CRD42020179703). KEY MESSAGESO_ST_ABSQuestionC_ST_ABSDid mental health symptoms worsen more for females or women than males or men in COVID-19? FindingsWe reviewed almost 65,000 citations and identified 12 studies that provided data to directly compare mental health symptom changes from pre-COVID-19 to during COVID-19 for females or women versus males or men. Statistically significant, but small, sex- or gender-based differences were found in 2 of 8 mental health outcomes. MeaningMental health changes among females or women were not significantly different from males or men for most outcomes, and differences that were identified were small and less than minimally important difference thresholds.

Comparison of Mental Health Symptoms prior to and during COVID-19: Evidence from a Living Systematic Review and Meta-analysis

ObjectivesThe rapid pace, high volume, and limited quality of mental health evidence that has been generated during COVID-19 poses a barrier to understanding mental health outcomes. We sought to summarize results from studies that compared mental health outcomes during COVID-19 to outcomes assessed prior to COVID-19 in the same cohort in the general population and in other groups for which data have been reported. DesignLiving systematic review. Data SourcesMEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), EMBASE (Ovid), Web of Science Core Collection: Citation Indexes, China National Knowledge Infrastructure, Wanfang, medRxiv (preprints), and Open Science Framework Preprints (preprint server aggregator). Eligibility criteria for selecting studiesFor this report, we included studies that compared general mental health, anxiety symptoms, or depression symptoms, assessed January 1, 2020 or later, to the same outcomes collected between January 1, 2018 and December 31, 2019. Any population was eligible. We required [≥] 90% of participants pre-COVID-19 and during COVID-19 to be the same or the use of statistical methods to address missing data. For population groups with continuous outcomes for at least two studies in an outcome domain, we conducted restricted maximum-likelihood random-effects meta-analyses. Worse COVID-19 mental health outcomes are reported as positive. Risk of bias of included studies was assessed using an adapted version of the Joanna Briggs Institute Checklist for Prevalence Studies. ResultsAs of April 11, 2022, we had reviewed 94,411 unique titles and abstracts and identified 137 unique eligible studies with data from 134 cohorts. Almost all studies were from high-income (105, 77%) or upper-middle income (28, 20%) countries. Among adult general population studies, we did not find changes in general mental health (standardized mean difference of change [SMDchange = 0.11, 95% CI -0.00 to 0.22) or anxiety symptoms (SMDchange = 0.05, 95% CI -0.04 to 0.13), but depression symptoms worsened minimally (SMDchange = 0.12, 95% CI 0.01 to 0.24). Among women or females, mental health symptoms worsened by minimal to small amounts in general mental health (SMDchange = 0.22, 95% CI 0.08 to 0.35), anxiety symptoms (SMDchange = 0.20, 95% CI 0.12 to 0.29), and depression symptoms (SMDchange = 0.22, 95% CI 0.05 to 0.40). Of 27 other analyses across outcome domains, among subgroups other than women or females, 5 analyses suggested minimal or small amounts of symptom worsening, and 2 suggested minimal or small symptom improvements. No other subgroup experienced statistically significant changes across outcome domains. In the 3 studies with data from March to April 2020 and later in 2020, symptoms either were unchanged from pre-COVID-19 at both time points or increased initially then returned to pre-COVID-19 levels. Heterogeneity measured by the I2 statistic was high (e.g., > 80%) for most analyses, and there was concerning risk of bias in most studies. ConclusionsHigh risk of bias in many studies and substantial heterogeneity suggest that point estimates should be interpreted cautiously. Nonetheless, there was general consistency across analyses in that most symptom change estimates were close to zero and not statistically significant, and changes that were identified were of minimal to small magnitudes. There were, however, small negative changes for women or females in all domains. It is possible that gaps in data have not allowed identification of changes in some vulnerable groups. Continued updating is needed as evidence accrues. Funding: Canadian Institutes of Health Research (CMS-171703; MS1-173070; GA4-177758; WI2-179944); McGill Interdisciplinary Initiative in Infection and Immunity Emergency COVID-19 Research Fund (R2-42). Registration: PROSPERO (CRD42020179703); registered on April 17, 2020.

Effects of COVID-19 Mental Health Interventions among Community-based Children, Adolescents, and Adults: A Living Systematic Review of Randomised Controlled Trials

BackgroundScalable interventions to address COVID-19 mental health are needed. Our objective was to assess effects of mental health interventions for community-based children, adolescents, and adults. MethodsWe searched 9 databases (2 Chinese-language) from December 31, 2019 to March 22, 2021. We included randomised controlled trials with non-hospitalised, non-quarantined participants of interventions to address COVID-19 mental health challenges. We synthesized results descriptively but did not pool quantitatively due to substantial heterogeneity of populations and interventions and concerns about risk of bias. FindingsWe identified 9 eligible trials, including 3 well-conducted, well-reported trials that tested interventions designed specifically for COVID-19 mental health challenges, plus 6 trials of standard interventions (e.g., individual or group therapy, expressive writing, mindfulness recordings) minimally adapted for COVID-19, all with risk of bias concerns. Among the 3 COVID-19-specific intervention trials, one (N = 670) found that a self-guided, internet-based cognitive-behavioural intervention targeting dysfunctional COVID-19 worry significantly reduced COVID-19 anxiety (standardized mean difference [SMD] 0.74, 95% CI 0.58 to 0.90) and depression symptoms (SMD 0.38, 95% CI 0.22 to 0.55) in Swedish general population participants. A lay-delivered telephone intervention for homebound older adults in the United States (N = 240) and a peer-moderated education and support intervention for people with a rare autoimmune condition from 12 countries (N = 172) significantly improved anxiety (SMD 0.35, 95% CI 0.09 to 0.60; SMD 0.31, 95% CI 0.03 to 0.58) and depressive symptoms (SMD 0.31, 95% CI 0.05 to 0.56; SMD 0.31, 95% CI 0.07 to 0.55) 6-weeks post-intervention, but these were not significant immediately post-intervention. No trials in children or adolescents were identified. InterpretationInternet-based programs for the general population and lay-or peer-delivered interventions for vulnerable groups may be effective, scalable options for public mental health in COVID-19. More well-conducted trials, including for children and adolescents, are needed. FundingCanadian Institutes of Health Research (CMS-171703; MS1-173070); McGill Interdisciplinary Initiative in Infection and Immunity Emergency COVID-19 Research Fund (R2-42). RegistrationPROSPERO (CRD42020179703); registered on April 17, 2020. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched for systematic reviews of randomised controlled trials of interventions to address mental health challenges in COVID-19. We used searches from our living systematic review, which were not limited by study design and reviewed citations through April 29, 2021 from MEDLINE, PsycINFO, CINAHL, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, medRxiv (preprints), and Open Science Framework Preprints (preprint server aggregator). We identified 4 systematic reviews of interventions for COVID-19 mental health with search dates between April and September 2020. None, however, included evidence from any completed randomised controlled trials on mental health interventions for community-based children, adolescents, or adults during COVID-19. Added value of this studyOur systematic review is the only living systematic review on COVID-19 community-based mental health interventions registered in PROSPERO and, to the best of our knowledge, the first systematic review to synthesize evidence on completed randomised controlled trials of COVID-19 mental health interventions. The sheer volume of evidence being published in COVID-19 poses a barrier to effective synthesis and policy response. We reviewed over 45,000 citations in any language and distilled this to 9 verified eligible community-based trials. Of these, there were 3 well-conducted trials of interventions designed specifically to be scalable to address challenges of public mental health in COVID-19. One trial showed that internet-based cognitive behavioural therapy in the Swedish general population (N = 670) reduced COVID-19 anxiety and symptoms of depression. Trials that tested a lay-delivered telephone support intervention for homebound older adults in the United States (N = 240) and a peer-moderated group intervention for people with a rare autoimmune condition from 12 countries (N = 172) also found that they improved mental health outcomes, although not all outcomes were statistically significant. Implications of all the available evidenceEffective, scalable, and feasibly delivered mental health interventions are needed for the general public and vulnerable groups as lockdown restrictions continue, even intermittently, and because COVID-19 mental health implications will likely persist beyond the pandemic. Although we identified only 3 high-quality trials, they demonstrated approaches that can be feasibly adopted to meet the needs of adults in the general public and vulnerable groups. The successful internet-based cognitive behavioural therapy intervention was made available to the Swedish general public free-of-charge following testing and suggests that online tools tailored for specific concerns in COVID-19 may represent an efficient way of addressing public mental health. Two lay-and peer-delivered interventions, consistent with pre-COVID-19 evidence, suggest that low-intensity, non-professionally delivered, support-oriented approaches can be leveraged among vulnerable groups. The absence of trials of interventions for children and adolescents underlines the need for evidence on scalable strategies for this population, including school-based approaches.

Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: A Systematic Review and Meta-analysis

BackgroundNasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs. MethodsWe systematically searched PubMed, Google Scholar, medRxiv, and bioRxiv (last retrieval October 1st, 2020) for comparative studies of alternative specimen types [saliva, oropharyngeal (OP), and nasal (NS) swabs] versus NP swabs for SARS-CoV-2 diagnosis using nucleic acid amplification testing (NAAT). A logistic-normal random-effects meta-analysis was performed to calculate % positive alternative-specimen, % positive NP, and % dual positives overall and in sub-groups. The QUADAS 2 tool was used to assess bias. ResultsFrom 1,253 unique citations, we identified 25 saliva, 11 NS, 6 OP, and 4 OP/NS studies meeting inclusion criteria. Three specimen types captured lower % positives [NS (0.82, 95% CI: 0.73-0.90), OP (0.84, 95% CI: 0.57-1.0), saliva (0.88, 95% CI: 0.81 - 0.93)] than NP swabs, while combined OP/NS matched NP performance (0.97, 95% CI: 0.90-1.0). Absence of RNA extraction (saliva) and utilization of a more sensitive NAAT (NS) substantially decreased alternative-specimen yield. ConclusionsNP swabs remain the gold standard for diagnosis of SARS-CoV-2, although alternative specimens are promising. Much remains unknown about the impact of variations in specimen collection, processing protocols, and population (pediatric vs. adult, late vs. early in disease course) and head-to head studies of sampling strategies are urgently needed.

Can we predict the severe course of COVID-19? A systematic review and meta-analysis of indicators of clinical outcome.

BackgroundCOVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. MethodsWe systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. ResultsOf 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). DiscussionThis comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making. SummaryIn this systematic review we meta-analyzed 88 articles for risk factors of ICU admission and mortality in COVID-19. We found age, cerebrovascular disease, CRP, LDH and cTnI are the most important risk-factors for ICU admission or mortality.

Evaluation of a home-based 7-day infection control strategy for healthcare workers following high-risk exposure to SARS-CoV-2: a cohort study

BackgroundEvidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to SARS-CoV-2. This study evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy. MethodsHCWs advised by their Infection Control or Occupational Health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May-September 2020. The strategy consisted of symptom-triggered nasopharyngeal SARS-CoV-2 RNA testing from day 0-6 post exposure, followed by standardized home-based nasopharyngeal swab and saliva testing on day 7. The NPV of this strategy was calculated for i) clinical COVID-19 diagnosis from day 8-14 post exposure, and for ii) asymptomatic SARS-CoV-2 detected by standardized nasopharyngeal swab and saliva specimens collected at days 9-10 and 14 post exposure. Interim results are reported in the context of a second wave threatening this essential workforce. ResultsAmong 30 HCWs enrolled to date (age 31{+/-}9 years, 24 [80.0%] female), 3 were diagnosed with COVID-19 by day 14 post exposure (secondary attack rate 10.0%), with all cases detected by the 7-day infection control strategy: NPV for subsequent clinical COVID-19 or asymptomatic SARS-CoV-2 detection by day 14 was 100.0% (95%CI: 93.1-100.0%). InterpretationAmong HCWs with high-risk exposure to SARS-CoV-2, a home-based 7-day infection control strategy may have a high NPV for subsequent COVID-19 and asymptomatic SARS-CoV-2 detection. While ongoing data collection and data sharing are needed to improve the precision of the estimated NPV, we report interim results to inform infection control strategies in light of a second wave threatening this essential workforce.

Comparison of Mental Health Symptoms Prior to and During COVID-19 among Patients with Systemic Sclerosis from Four Countries: A Scleroderma Patient-centered Intervention Network (SPIN) Cohort Study

BackgroundNo studies have reported comparisons of mental health symptoms prior to and during COVID-19 in vulnerable populations. Objectives were to compare anxiety and depression symptoms among people with a pre-existing medical condition, the autoimmune disease systemic sclerosis (SSc; scleroderma), including continuous change scores, proportion with change [≥] 1 minimal clinically important difference (MCID), and factors associated with changes, including country. MethodsPre-COVID-19 Scleroderma Patient-centered Intervention Network Cohort data were linked to COVID-19 data collected April 9 to April 27, 2020. Anxiety symptoms were assessed with the PROMIS Anxiety 4a v1.0 scale (MCID = 4 points) and depression symptoms with the Patient Health Questionnaire-8 (MCID = 3 points). Multiple linear and logistic regression were used to assess factors associated with continuous change and change[≥] 1 MCID. FindingsAmong 435 participants (Canada = 98; France = 159; United Kingdom = 50; United States = 128), mean anxiety symptoms increased 4.9 points (95% confidence interval [CI] 4.0 to 5.7). Depression symptom change was negligible (0.3 points; 95% CI -0.7 to 0.2). Compared to France, adjusted scores from the United States and United Kingdom were 3.8 points (95% CI 1.7 to 5.9) and 2.9 points higher (95% CI 0.0 to 5.7); scores for Canada were not significantly different. Odds of increasing by [≥] 1 MCID were twice as high for the United Kingdom (2.0, 95% CI 1.0 to 4.2) and United States (1.9, 95% CI 1.1 to 3.2). Participants who used mental health services pre-COVID had adjusted increases 3.7 points (95% CI 1.7 to 5.7) less than other participants. InterpretationAnxiety symptoms, but not depression symptoms, increased dramatically during COVID-19 among people with a pre-existing medical condition. Increase was larger in the United Kingdom and United States than in Canada and France but substantially less for people with pre-COVID-19 mental health treatment. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe referred to a living systematic review that is evaluating mental health changes from pre-COVID-19 to COVID-19 by searching 7 databases, including 2 Chinese language databases, plus preprint servers, with daily updates (https://www.depressd.ca/covid-19-mental-health). As of June 13, 2020, only 5 studies had compared mental health symptoms prior to and during COVID-19. In 4 studies of university students, there were small increases in depression or general mental health symptoms but minimal or no increases in anxiety symptoms. A general population study from the United Kingdom reported a small increase in general mental health symptoms but did not differentiate between types of symptoms. No studies have reported changes from pre-COVID-19 among people vulnerable due to pre-existing medical conditions. No studies have compared mental health changes between countries, despite major differences in pandemic responses. Added value of this studyWe evaluated changes in anxiety and depression symptoms among 435 participants with the autoimmune condition systemic sclerosis and compared results from Canada, France, the United Kingdom, and the United States. To our knowledge, this is the first study to compare mental health symptoms prior to and during COVID-19 in any vulnerable population. These are the first data to document the substantial degree to which anxiety symptoms have increased and the minimal changes in depression symptoms among vulnerable individuals. It is also the first study to examine the association of symptom changes with country of residence and to identify that people receiving pre-COVID-19 mental health services may be more resilient and experience less substantial symptom increases than others. Implications of all the available evidenceAlthough this was an observational study, it provided evidence that vulnerable people with a pre-existing medical condition have experienced substantially increased anxiety symptoms and that these increases appear to be associated with where people live and, possibly, different experiences of the COVID-19 pandemic across countries. By comparing with evidence from university samples, which found that depression symptoms were more prominent, these data underline the need for accessible interventions tailored to specific needs of different populations. They also suggest that mental health treatments may help people to develop skills or create resilience, which may reduce vulnerability to major stressors such as COVID-19.