title: Keeping it close: The role of a Campus COVID Support Team (CCST) in sustaining a safe and healthy university campus during COVID-19

abstract:
It has been over 24 months since the start of the COVID-19 pandemic forced university campuses to shut down and then reopen under new safety guidelines. Now as we move into the subsequent years of the pandemic, we can look back and evaluate what has worked, improvements to be made, and plans for providing a sustained response for a campus community. In this article we detail one campus response to the COVID-19 pandemic and directions being taken to ensure a sustained campus COVID support team (CCST) is in hand to ensure the health and safety of the university community. The CCST was created to serve as a one-stop-shop to help the university community navigate COVID-19 policies and procedures. The responsibilities of the CCST include conducting case investigations for any positive COVID-19 tests within the university community, contact tracing for authorized university affiliates, epidemiological surveillance and mitigation efforts, and communication through real-time analysis and dashboards. Continuous monitoring procedures demonstrated the CCST conducted all case investigations within the post-testing 24-hour window, thus keeping the university test-positivity rate below 3%. Quality improvement surveys demonstrated a high level of satisfaction with the CCST efforts and provided areas for improvement and sustainability. Having a public health faculty led CCST enabled the university to act swiftly when COVID-19 positive cases were emerging and deter widespread campus COVID-19 outbreaks. The CCST timeliness and connectivity to the campus has demonstrated benefits to the health and safety of the campus.

HighlightsO_LIUniversities are their own communities and having on campus COVID support teams can mitigate potential COVID-19 outbreaks.
C_LIO_LIHaving a public health driven Campus COVID Support Team that can conduct case investigations within 24 hours of a positive test result has demonstrated benefits to taking responsive measures.
C_LIO_LIContinuous quality improvement efforts including surveys of the Campus COVID Support Team should be implemented for any COVID service efforts.
C_LI


title: Acute exercise induces natural killer cell mobilization but not infiltration into prostate cancer tissue in humans

abstract: The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune responsive tumor entities.

category: sports medicine


title: A role for super-spreaders in carrying malaria parasites across the months-long dry season

abstract: In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some individuals who experience prolonged carriage of parasites and are thought to  seed infection in the next transmission season. We use a combination of mathematical simulations and data analysis to characterise dry season carriers and their role in the subsequent transmission season. Simulating the life-history of individuals experiencing repeated exposure to infection predicts that dry season carriage is more likely in the oldest, most exposed and most immune individuals. This hypothesis is supported by data from a longitudinal study in Mali that shows that carriers are significantly older, experience a higher biting rate at the beginning of the transmission season and develop clinical malaria later than non-carriers. Further, since the most exposed individuals in a community are most likely to be dry season carriers, we show that this is predicted to enable a more than 2-fold faster spread of parasites into the mosquito population at the start of the subsequent wet season.

category: infectious diseases


title: A 5-year review of incidence, presentation and management of Bartholin gland cysts and abscesses in a tertiary hospital, Yenagoa, South-South Nigeria

abstract:
BackgroundBartholin gland cysts and abscesses are common in women of reproductive age and declines after menopause. Organisms implicated in Bartholin abscess include, Neisseria gonorrhoeae, Chlamydia trachomatis, Escherichia coli, Staphylococcus aureus and Bacterioides spp.

AimTo determine the incidence, presentation and management of Bartholin gland cysts and abscesses at the Federal Medical Centre, Yenagoa, Bayelsa State, South-South Nigeria, over a five-year period.

Settings and DesignThis retrospective study was conducted in the Gynaecological Unit of the Federal Medical Centre, Yenagoa, Bayelsa State, South-South, Nigeria, between January 1, 2016 and December 31, 2020.

Materials and MethodsRelevant data were retrieved, entered into a pre-designed proforma, and analysed.

Statistical AnalysisStatistical Package for the Social Sciences version 25.0 was used for data analysis. Results were presented in frequencies and percentages for categorical variables.

ResultsThere were 2,478 gynaecological cases managed in our Centre; out of which there were 26 cases of Bartholin cyst and abscess, giving an incidence of 1.05%. Most of the women were [≤] 30 years (14, 53.8%), single (17, 65.4%), nulliparous (13, 50.0%), traders (11, 42.3%), with only primary/secondary education (18, 69.2%). The left Bartholin gland was the most frequently affected (17, 65.4%). A positive microbial culture was obtained in 84% of cases, with Staphylococcus aureus and Escherichia coli being the isolated organisms. Marsupialisation was the treatment modality in all the patients.

ConclusionWomen of reproductive age-group should be counselled on this condition and encouraged to keep good perineal hygiene and better sexual conduct so as to reduce the risk of Bartholin cysts and abscesses.

category: obstetrics and gynecology


title: Ultrasonic Artificial Intelligence Shows Statistically Equivalent Performance for Thyroid Nodule Diagnosis to Fine Needle Aspiration Cytopathology and BRAFV600E Mutation Analysis Combined

abstract:
ObjectiveTo investigate the difference between an artificial intelligence (AI) system, fine-needle aspiration (FNA) cytopathology, BRAFV600E mutation analysis and combined method of the latter two in thyroid nodule diagnosis.

MethodsUltrasound images of 490 thyroid nodules (378 patients) with postsurgical pathology or twice of consistent combined FNA examination outcomes with a half-year interval, which were considered as gold standard, were collected and analyzed. The diagnostic efficacies of an AI diagnostic system and FNA-based methods were evaluated in terms of sensitivity, specificity, accuracy,{kappa} coefficient compared to the gold standard.

ResultsThe malignancy threshold of 0.53 for an AI system was selected according to the optimization of Youden index based on a retrospective cohort of 346 nodules and then applied for a prospective cohort of 144 nodules. The combined method of FNA cytopathology according to Bethesda risk stratification system and BRAFV600E mutation analysis showed no significant difference in comparison with the AI diagnostic system in accuracy for both the retrospective and prospective cohort in our single center study. Besides, for the 33 indeterministic Bethesda system category III and IV nodules included in our study, the AI system showed no significant difference in comparison with the BRAFV600E mutation analysis.

ConclusionThe evaluated AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with and BRAFV600E mutation analysis. Given its advantages in ease of operation, time efficiency, and noninvasiveness for thyroid nodule screening as well as the wide availability of ultrasonography, it can be widely applied in all levels of hospitals and clinics to assist radiologists for thyroid nodule diagnosis and is expected to reduce the need for relatively invasive FNA biopsies and thereby reducing the associated risks and side effects as well as to shorten the diagnostic time.

category: oncology


title: Omicron infection induces low-level, narrow-range SARS-CoV-2 neutralizing activity

abstract:
BackgroundThe rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics.

MethodsConvalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants.

FindingsPrior vaccination or infection with the Alpha or to a lesser extent Delta strains conferred robust neutralizing titers against most variants, albeit more weakly against Beta and even more Omicron. In contrast, Omicron convalescent serums only displayed low level of neutralization activity against the cognate virus and were unable to neutralize other SARS-CoV-2 variants.

InterpretationModerately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination.

FundingEPFL COVID Fund; private foundation advised by CARIGEST SA; Private Foundation of the Geneva University Hospitals; General Directorate of Health of the canton of Geneva, the Swiss Federal Office of Public Health.


title: Automatized and combined HIV, HBV, HCV, and syphilis testing among illegal gold miners in French Guiana using a standardized dried blood device

abstract:
BackgroundBlood spotted onto filter paper can be easy collected outside healthcare facilities and shipped to central laboratory for serological testing. However, dried blood testing generally requests manual processing for elution. In this study, we used a standardized blood collection device combined with an automatized elution system to test illegal gold miners living in French Guiana for HIV, HBV, HCV and syphilis.

Material and MethodsWe included 378 participants in five resting sites of illegal gold mining. Serological status was determined by testing serum samples. Blood collected on the Ser-Col device (Labonovum), was eluted using an automated system (SCAUT Ser-Col automation, Blok System Supply) and an automatized analyzer (Alinity i, Abbott). Ser-Col results were compared to serum considered as the reference, and dried blood spot samples were processed manually.

ResultsTwo participants tested positive for HIV (0.5%), eight tested positive for hepatitis B surface antigen (HBsAg), four were weakly positive for anti-HCV antibodies (1%) but negative for HCV RNA, and 47 tested positive for syphilis (12.4%). We observed a full concordance of Ser-Col and DBS results for HIV diagnosis compared to serum results. Ser-Col and DBS samples tested positive in seven HBsAg carriers and negative for one participants having a low HBsAg level in serum (0.5 IU/mL). Three hundred and sixty-eight participants uninfected by HBV tested negative for HBsAg (99.5%). Two Ser-Col samples and two other DBS samples positive tested positive in HBV uninfected participants (false positive results with low S/CO indexes). All participants tested negative for HCV in Ser-Col and DBS samples, including in dried blood samples from the four participants tested low positive for HCV antibodies and HCV RNA negative in serum. The threshold of the treponemal assay was optimized for dried blood sample testing. Among syphilis seropositive participants, 35 (74.61%) tested positive for treponemal antibodies in Ser-Col and DBS samples. Among participants seronegative for syphilis, 326 (98.4%) and 325 (98.1%) tested negative in Ser-Col and DBS samples, respectively.

ConclusionThe Ser-Col method allows automatized dried blood testing of HIV, HBV, HCV and syphilis with performances comparable to DBS. Automated approaches to test capillary blood transported on dried blood devices may facilitate large scale surveys and improve testing of populations living in remote areas for infectious diseases.


title: Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages

abstract: South Africas fourth COVID-19 wave was driven predominantly by three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern. We have now identified two new lineages, BA.4 and BA.5. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del, L452R, F486V and the wild type amino acid at Q493. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure with the TaqPath COVID-19 qPCR assay. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa from the first week of April 2022 onwards. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.07 - 0.09) and 0.12 (95% CI: 0.09 - 0.15) per day respectively over BA.2 in South Africa.


title: Real-World Progression-Free Survival as an Endpoint in Advanced Non-Small-Cell Lung Cancer: Replicating Atezolizumab and Docetaxel Arms of the OAK Trial Using Data Derived From Electronic Health Records

abstract:
BackgroundEvaluating cancer treatments in real-world data (RWD) requires informative endpoints. Due to non-standardized data collection in RWD, it is unclear if and when common oncology endpoints are approximately equivalent to their clinical trial analogues. This study used RWD to replicate both the atezolizumab and docetaxel arms of the OAK trial. Outcomes using progression-free survival (PFS) derived from abstracted physicians notes in RWD (rwPFS) were then compared against PFS outcomes derived according to Response Evaluation Criteria in Solid Tumors (RECIST) from the clinical trial (ctPFS).

MethodsAtezolizumab and docetaxel arms of the phase III OAK RCT (NCT02008227) were replicated in a US nationwide real-world database by applying selected OAK inclusion/exclusion criteria, followed by adjustment for baseline prognostic variables using propensity score-based methods. Multiple rwPFS definitions were characterized and a definition was chosen that was acceptable from both clinical and data analysis perspectives. Concordance of outcomes was assessed using Kaplan-Meier (KM) medians and hazard ratios (HRs).

ResultsOverall, 133 patients receiving atezolizumab and 479 patients receiving docetaxel were selected for the RWD cohort. After adjustment, prognostic variables were balanced between RCT arms and corresponding RWD cohorts. Comparing rwPFS against ctPFS outcomes in terms of KM median and HR showed better concordance for docetaxel (2.99 vs 3.52 months; HR, 0.99, 95% CI, 0.85-1.15) than for atezolizumab (3.71 vs 2.76 months; HR, 0.8, 95% CI 0.61-1.02). The latter improved when events labelled "pseudo-progression" were excluded from the RWD (im-rwPFS) and immune-modified RECIST PFS (im-ctPFS) was used in the RCT Atezolizumab data (4.24 vs 4.14 months; HR, 0.95, 95% CI, 0.70-1.25). These findings were robust across several sensitivity analyses.

ConclusionsWhile rwPFS and ctPFS were similar under docetaxel treatment, this was only the case for atezolizumab when immune-modified progression criteria were used, suggesting that similarity of RWD endpoints to their clinical trial analogues depends on drug category and possibly other factors. Replication of RCTs using RWD and comparison of outcomes can be used as a tool for characterizing RWD endpoints. Additional studies are needed to verify these findings and to better understand the conditions for approximate numerical equivalence of rwPFS and ctPFS endpoints.

category: epidemiology


title: GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease

abstract:
The association between glucocerebrosidase (GCase), encoded by GBA, and Parkinsons disease highlights the role of the lysosome in Parkinsons disease pathogenesis. Genome-wide association studies (GWAS) in Parkinsons disease have revealed multiple associated loci, including the GALC locus on chromosome 14. GALC encodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whether GALC is the gene driving the association in the chromosome 14 locus, and if so, by which mechanism.

We first aimed to examine whether variants in the GALC locus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinsons Progression Markers Initiative study, followed by a meta-analysis with a total of 1,123 Parkinsons disease patients and 576 controls with available data on GalCase activity. We further analyzed the effects of common GALC variants on expression and GalCase activity using colocalization methods. Mendelian randomization was used to study whether GalCase activity may be causal in Parkinsons disease. To study the role of rare GALC variants we analyzed sequencing data from a total of 5,028 Parkinsons disease patients and 5,422 controls. Additionally, we studied the functional impact of GALC knock-out on alpha-synuclein accumulation and on GCase activity in neuronal cell models and performed in silico structural analysis of common GALC variants associated with altered GalCase activity.

The top hit in Parkinsons disease GWAS in the GALC locus, rs979812, is associated with increased GalCase activity (b=1.2; se=0.06; p=5.10E-95). No other variants outside the GALC locus were associated with GalCase activity. Colocalization analysis demonstrated that rs979812 was also associated with increased GalCase expression. Mendelian randomization suggested that increased GalCase activity may be causally associated with Parkinsons disease (b=0.025, se=0.007, p=0.0008). We did not find an association between rare GALC variants and Parkinsons disease. GALC knockout using CRISPR-Cas9 did not lead to alpha-synuclein accumulation, further supporting that increased rather than reduced GalCase levels may be associated with Parkinsons disease. The structural analysis demonstrated that the common variant p.I562T may lead to improper maturation of GalCase affecting its activity.

Our results nominate GALC as the gene associated with Parkinsons disease in this locus and suggest that the association of variants in the GALC locus may be driven by their effect of increasing GalCase expression and activity. Whether altering GalCase activity could be considered as a therapeutic target should be further studied.

category: neurology


title: Dopamine D1 agonist effects in late-stage Parkinson's disease

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSCurrent pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinsons disease (LsPD) patients whose daily life depends primarily on caregivers and palliative care. Clinical metrics inadequately gauge efficacy in LsPD patients.

ObjectiveExplore if a D1/5 dopamine agonist will have efficacy in LsPD that will be detected most sensitively by caregivers in a phase I study.

MethodsA double-blind controlled phase Ia/b study compared the D1/5 agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. Throughout the study, caregivers were with the patients. Assessments included standard quantitative scales of motor function (MDS-UPDRS-III), alertness (Glasgow Coma and Stanford Sleepiness Scales), and cognition (Severe Impairment and Frontal Assessment Batteries) at baseline (Day 1) and thrice daily during drug testing (Days 2 and 3). Clinicians and caregivers completed clinical impression of change questionnaires, and caregivers participated in a qualitative exit interview. Blinded triangulation of quantitative and qualitative data was used to integrate findings.

ResultsNeither traditional scales, nor clinician impression of change, detected consistent differences between treatments in the five participants who completed the study. Conversely, the overall caregiver data strongly favored PF-06412562 over levodopa in four of five patients. The most meaningful improvements converged on motor, alertness, and engagement.

ConclusionD1/5 agonists may offer potential benefit for LsPD patients. Caregiver perspectives with mixed method analyses may overcome limitations in standard rater/clinician-based evaluations. Further studies are warranted and need to integrate caregiver input as an essential component of outcome evaluations.

Trial Registration#ClinicalTrials.gov: NCT03665454


title: Genome-wide investigation of maximum habitual alcohol intake (MaxAlc) in 247,755 European and African Ancestry U.S. Veterans informs the relationship between habitual alcohol consumption and alcohol use disorder.

abstract: Importance: Alcohol genome-wide association studies (GWAS) have generally focused on alcohol consumption and alcohol use disorder (AUD); few have examined habitual drinking behaviors like maximum habitual alcohol intake (MaxAlc). Objective: Identify MaxAlc loci and elucidate the genetic architecture across alcohol traits. Design: The MaxAlc GWAS was performed in Million Veteran Program (MVP) participants enrolled from January 10, 2011 to September 30, 2020. Ancestry-specific GWAS were conducted in European (EUR) (n=218,623) and African (AFR) (n=29,132) ancestry subjects, then meta-analyzed (N=247,755). Linkage-disequilibrium score regression (LDSC) was used to estimate SNP-heritability and genetic correlations (rg) with other alcohol and psychiatric traits. Genomic structural equation modeling (gSEM) was used to evaluate genetic relationships between MaxAlc and other alcohol traits. Mendelian randomization (MR) was used to examine causal relationships. MTAG (multi-trait analysis of GWAS) was used to analyze MaxAlc and problematic alcohol use (PAU) jointly. Setting: The study was performed in a sample of U.S military Veterans. Participants: Participants were 92.68% male and had mean age=65.92 (SD=11.70). 36.92% reported MaxAlc [≥] the binge-drinking threshold. Main Outcomes(s) and Measure(s): MaxAlc was defined from survey item: 'in a typical month, what is/was the largest number of drinks of alcohol you may have had in one day?' with ordinal responses from 0 [≥] 15 drinks. Results: The MaxAlc GWAS resulted in 15 genome-wide significant (GWS) loci. Top associations in EUR and AFR were with known functional variants ADH1B*rs1229984 (p=3.12x10-104) and rs2066702 (p=6.30x10-17), respectively. Multiple novel associations were found. The SNP-heritability was 6.65% (s.e.=0.41%) in EUR and 3.42% (s.e.=1.46%) in AFR. MaxAlc was positively correlated with PAU (rg=0.79; p=3.95x10-149) and AUD (rg=0.76; p=1.26x10-127), and had negative rg with 'alcohol usually taken with meals' (rg=-0.53; p=1.40x10-50). For psychiatric traits, MaxAlc had the strongest rg with suicide attempt (rg=0.40; p=3.02x10-21). gSEM supported a two-factor model with MaxAlc loading on a factor with PAU and AUD, and other alcohol consumption measures loading a separate factor. MR supported a small causal effect of MaxAlc on the liver enzyme gamma-glutamyltransferase ({beta}=0.012; p=2.66x10-10). MaxAlc MTAG resulted in 31 GWS loci. Conclusions and Relevance: MaxAlc closely aligns genetically with the etiology of problematic alcohol use traits.

category: genetic and genomic medicine


title: SENSITIVITY ANALYSIS OF A TUBERCULOSIS (TB) MATHEMATICAL MODEL

abstract: In this work, we have constructed a Mathematical model for the transmission dynamics of tuberculosis TB. Feasibility and positivity of solutions of the model are determined and it is established that the model is well posed and that the solutions are all positive. The disease-free equilibrium (DFE) is also determined and the basic reproduction number R0 is computed. Sensitivity analysis of the basic reproduction number is conducted to find parameters of the model that are most sensitive and should be targeted by intervention strategies. It was therefore, observed through sensitivity analysis that TB induced death (d) has a high impact on R0 and varies inversely with R0. Graphical simulation of the model parameters was performed. It was observed that model parameters such as infection rate ({beta}), recruitment rate ({pi}) and rate of movement from latent to active TB () are directly proportional to the basic reproduction numberR0. Finally, it is observed that the basic reproduction number R0 is a decreasing function of the recovery rate ({gamma}) and natural death rate ().


title: Medical journeys of victims of exploitation and trafficking: a retrospective cohort study using a large multi-state dataset and new ICD-10 codes

abstract:
BackgroundTrafficking and exploitation for sex or labor affects millions of persons worldwide, but their use of the healthcare system is not characterized systematically. In 2018 new ICD-10 codes were implemented in the US for diagnosis of patients who were victims of trafficking or exploitation but todate no comprehensive study reported on their medical journeys. Our objective was to examine the extent to which newly implemented ICD-10 codes pertaining to human trafficking were being used in the healthcare system, and to characterize the care received by the victims.

Methods and FindingsDatabase search of a large US health insurer that contained approximately 43 million patients holding commercial or government-provided health insurance across the United States (US). For the dates 2018-09-01 to 2022-03-01, the dataset was found to contain 3,967 instances of the ICD-10 codes. In 31% of the cases, the codes were used as the principal or admitting diagnosis. Regression analysis of the codes found a 2% increase in the adoption of these codes. The codes were used by 1,532 distinct providers, the majority in non-hospital settings.

The data contained 2301 patients of which 1025 were treated for recent exploitation or trafficking, which corresponds to identification of 13 new patients each week. Of the latter patients, 90.1% were victims of sexual exploitation, and 9.9% victims of labor exploitation. The patients were predominantly female (81%), insured by Medicaid (60%) and the median age was 20 (interquartile range: 15-35). Healthcare utilization over 12 months after diagnosis of trafficking was $32,192 (standard deviation: $160,730) - much greater than average for Medicaid patients ($6,556 per year in 2019). The victims were characterized by a high prevalence of mental health conditions, high utilization of the emergency department, and these persisted after diagnosis of exploitation. Surprisingly, 57% of the victims were first diagnosed outside hospitals, primarily during office and psychiatric visits, and only 25% were first diagnosed during an emergency department visit.

ConclusionsThe new ICD-10 codes provide valuable insights into the profiles and medical journeys of victims of trafficking. However, adoption of the codes is not widespread, increasing by only 2% per year and the majority of the victims are likely still not diagnosed by the new codes. Greater adoption, when consistent with patient safety, may improve care coordination and outcomes.

category: pediatrics


title: The impact of post-traumatic stress disorder in pharmacological intervention outcomes for adults with bipolar disorder: a protocol for a systematic review and meta-analysis.

abstract:
BackgroundRecent data indicates high prevalence of post-traumatic stress disorder (PTSD) in bipolar disorder (BD). PTSD may play a role in poor treatment outcomes and quality of life for people with BD. Despite this, few studies have examined the pharmacological treatment interventions and outcomes for this comorbidity. This systematic review will bring together currently available evidence regarding the impact of comorbid PTSD on pharmacological treatment outcomes in adults with BD.

MethodsA systematic search of Embase, MEDLINE Complete, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be conducted to identify randomised and non-randomised studies of pharmacological interventions for adults with diagnosed bipolar disorder and PTSD. Data will be screened and extracted by two independent reviewers. Literature will be searched from the creation of the databases until April 1 2021. Risk of bias will be assessed using the Newcastle-Ottawa Scale and the Cochrane Collaborations Risk of Bias tool. A meta-analysis will be conducted if sufficient evidence is identified in the systematic review. The meta-analysis will employ a random-effects model and be evaluated using the I2 statistic.

DiscussionThis review and meta-analysis will be the first to systematically explore and integrate the available evidence on the impact of PTSD on pharmacological treatments and outcome in those with BD. The results and outcomes of this systematic review will provide directions for future research and be published in relevant scientific journals and presented at research conferences.

Systematic review registrationThe protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020182540).

category: psychiatry and clinical psychology


title: Bridging Structural MRI with Cognitive Function for Individual Level Classification of Early Psychosis via Deep Learning

abstract: Recent efforts have been made to apply machine learning and deep learning approaches to the automated classification of schizophrenia using structural magnetic resonance imaging (sMRI) at the individual level. However, these approaches are less accurate on early psychosis (EP) since there are mild structural brain changes at early stage. As cognitive impairments is one main feature in psychosis, in this study we apply a multi-task deep learning framework using sMRI with inclusion of cognitive assessment to facilitate the classification EP patients from healthy individuals. Unlike previous studies, we used sMRI as the direct input to perform EP classifications and cognitive estimations. The proposed model does not require time-consuming volumetric or surface based analysis and can provide additionally cognition predictions. Extensive experiments were conducted on a sMRI data set with a total of 77 subjects (38 EP patients and 39 healthy controls), and we achieved 74.9{+/-}4.3% five-fold cross-validated accuracy and an area under the curve of 71.1{+/-}4.1% on EP classification with the inclusion of cognitive estimations. We reveal the feasibility of automated cognitive estimation using sMRI by deep learning models, and also demonstrate the implicit adoption of cognitive measures as additional information to facilitate EP classifications from healthy controls.


title: Comparative analysis of the outcomes of COVID-19 between patients infected with SARS-CoV-2 Omicron and Delta variants: a retrospective cohort study

abstract:
BackgroundThe SARS-CoV-2 Omicron variant has replaced the previously dominant Delta variant because of high transmissibility. It is responsible for the current increase in the COVID-19 infectivity rate worldwide. However, studies on the impact of the Omicron variant on the severity of COVID-19 are still limited in developing countries. Here, we compared the outcomes of patients infected with SARS-CoV-2 Omicron and Delta variants and associated with prognostic factors, including age, sex, comorbidities, and smoking.

MethodsWe involved 352 patients, 139 with the Omicron variant and 213 with the Delta variant. The whole-genome sequences of SARS-CoV-2 were conducted using the Illumina MiSeq next-generation sequencer.

ResultsCt value and mean age of COVID-19 patients were not significantly different between both groups (Delta: 20.35 {+/-} 4.07 vs. Omicron: 20.62 {+/-} 3.75; p=0.540; and Delta: 36.52 {+/-} 21.24 vs. Omicron: 39.10 {+/-} 21.24; p=0.266, respectively). Patients infected with Omicron and Delta variants showed similar hospitalization (p=0.433) and mortality rates (p=0.565). Multivariate analysis showed that older age ([≥]65 years) had higher risk for hospitalization (OR=3.67 [95% CI=1.22-10.94]; p=0.019) and fatalities (OR=3.93 [95% CI=1.35-11.42]; p=0.012). In addition, patients with cardiovascular disease had higher risk for hospitalization (OR=5.27 [95% CI=1.07-25.97]; p=0.041), whereas patients with diabetes revealed higher risk for fatalities (OR=9.39 [95% CI=3.30-26.72]; p=<0.001).

ConclusionsOur study shows that patients infected with Omicron and Delta variants reveal similar clinical outcomes, including hospitalization and mortality. In addition, our findings further confirm that older age, cardiovascular disease, and diabetes are strong prognostic factors for the outcomes of COVID-19 patients.

category: public and global health


title: The efficacy of soap against schistosome cercariae: A systematic review

abstract:
BackgroundSchistosomiasis is a parasitic disease that is endemic in 78 countries and affects almost 240 million people worldwide. It has been acknowledged that an integrated approach that goes beyond drug treatment is needed to achieve control and eventual elimination of the disease. Improving hygiene has been encouraged by World Health Assembly, and one aspect of good hygiene is using soap during water-contact activities, such as bathing and doing laundry. This hygiene practice might directly reduce the skin exposure to cercariae at transmission sites. A qualitative systematic review was carried out to investigate the efficacy of soap against schistosome cercariae and to identify the knowledge gaps surrounding this topic.

MethodologySix online databases were searched between 5th and 8th July of 2021. Records returned from these databases were screened to remove duplicates, and the remaining records were classified by reading titles, abstracts, and full-texts to identify the included studies. The results were categorised into two groups based on two different protective mechanisms of soap (namely, damage to cercariae and protection of skin).

ConclusionsLimited research has been conducted on the efficacy of soap against schistosome cercariae and only 11 studies met the criteria to be included in this review. The review demonstrates that soap has the potential of protecting people against schistosome cercariae and there are two protective aspects: (1) soap affects cercariae adversely; (2) soap on the skin prevents cercariae from penetrating the skin. Both aspects of protection were influenced by many factors, but the differences in the reported experimental conditions, such as the cercarial endpoint measurement used and the cercaria numbers used per water sample, lead to low comparability between the previous studies. This review demonstrates that more evidence is needed to inform hygiene advice for people living in schistosomiasis endemic areas.

Author summarySchistosomiasis affects millions of people living in low- and middle-income countries lacking safe access to water, sanitation and hygiene (WASH). Schistosomiasis is mainly controlled by drug treatment with praziquantel, but people become infected again if they continue to come into contact with cercaria-contaminated water. Despite all the efforts that have been made, this disease remains a major public health problem in disease-endemic regions. The use of soap during water contact, as part of good hygiene practice, may be an effective complementary control method as it might reduce the penetration of schistosome cercariae into the skin, thereby reducing the likelihood of reinfection. We conducted a systematic review to summarise previous research into the efficacy of soap against schistosome cercariae, and to identify current knowledge gaps to inform future studies. The information gathered from this review can guide hygiene advice regarding soap use in endemic areas to reduce the spread of schistosomiasis.


title: The impact of relationship to cancer patient and extent of caregiving on adherence to cancer screening in a diverse inner-city community

abstract:
IntroductionThe number of individuals called upon to provide support for cancer patients within their personal networks is steadily increasing. Prior studies show that caregiver screening rates either decrease due to caregiving demands and associated fatalism or increase due to risk perception and healthcare involvement. However, there remains a gap in research in understanding how cancer screening relates to extent of caregiving and relationship to cancer patient, particularly non-family/spouse. This study aims to assess the impact of degrees of relationship to cancer patient(s) and extent of caregiving on adherence to breast, cervical, prostate, and colorectal cancer screening guidelines.

MethodsParticipants of Bronx, New York were recruited online or through community events to complete a set of core items adapted from the NCI Health Information National Trends Survey and other sources. Logistic regression analyses identified factors associated with variation in screening.

ResultsAnalyses were based on 1430 participants (73% female, mean age 50 years, 43% Hispanic). An unexpectedly large proportion had cancer within their families (72%) and/or provided some support to a cancer patient (79%). Four support patterns were found-none, emotional support only, less intensive, and more intensive support. Women who provided emotional support only were less likely to be screened for breast and cervical cancer. Among more active caregivers, cervical and prostate cancer screening were greater among those who provided more intensive support.

ConclusionsHaving family or friends with cancer is a normative experience that affects ones own preventive care. Those with a family member or spouse with cancer have increased personal screening. As involvement in cancer caregiving deepens, ones own screening rises. Caregivers that provided only emotional support are the exception, potentially because they have greater distance from the cancer experience. Findings suggest the potential value of tailoring interventions to address personal experiences with cancer caregiving.


title: Artificial Intelligence for context-aware surgical guidance in complex robot-assisted oncological procedures: an exploratory feasibility study

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSComplex oncological procedures pose various surgical challenges including dissection in distinct tissue planes and preservation of vulnerable anatomical structures throughout different surgical phases. In rectal surgery, a violation of dissection planes increases the risk of local recurrence and autonomous nerve damage resulting in incontinence and sexual dysfunction. While deep learning-based identification of target structures has been described in basic laparoscopic procedures, feasibility of artificial intelligence-based guidance has not yet been investigated in complex abdominal surgery.

MethodsA dataset of 57 robot-assisted rectal resection (RARR) videos was split into a pre-training dataset of 24 temporally non-annotated videos and a training dataset of 33 temporally annotated videos. Based on phase annotations and pixel-wise annotations of randomly selected image frames, convolutional neural networks were trained to distinguish surgical phases and phase-specifically segment anatomical structures and tissue planes. To evaluate model performance, F1 score, Intersection-over-Union (IoU), precision, recall, and specificity were determined.

ResultsWe demonstrate that both temporal (average F1 score for surgical phase recognition: 0.78) and spatial features of complex surgeries can be identified using machine learning-based image analysis. Based on analysis of a total of 8797 images with pixel-wise target structure segmentations, mean IoUs for segmentation of anatomical target structures range from 0.09 to 0.82 and from 0.05 to 0.32 for dissection planes and dissection lines throughout different phases of RARR in our analysis.

ConclusionsImage-based recognition is a promising technique for surgical guidance in complex surgical procedures. Future research should investigate clinical applicability, usability, and therapeutic impact of a respective guidance system.

category: surgery


title: Decoding natural gait cycle in Parkinson's disease from cortico-subthalamic field potentials

abstract: Human bipedal walking is a complex motor behavior that requires precisely timed alternating activity across multiple nodes of the supraspinal network. However, understanding the neural dynamics that underlie walking is limited. We investigated the cortical-subthalamic circuit dynamics of overground walking from three patients with Parkinsons disease without major gait impairments. All patients were implanted with chronic bilateral deep brain stimulation leads in the subthalamic nucleus (STN) and electrocorticography paddles overlying the primary motor (M1) and sensory (S1) cortices. Local field potentials were wirelessly streamed through implanted bidirectional pulse generators during overground walking and synchronized to external gait kinematics sensors. We found that the STN displays increased low frequency (4-12 Hz) spectral power between ipsilateral heel strike to contralateral leg swing. Furthermore, the STN shows increased theta frequency (4-8 Hz) coherence with M1 through the initiation and early phase of contralateral leg swing. Our findings support the hypothesis that oscillations from the basal ganglia and cortex direct out-of-phase, between brain hemispheres in accordance with the gait cycle. In addition, we identified patient-specific, gait-related biomarkers in both STN and cortical areas at discrete frequency bands. These field potentials support classification of left and right gait events. These putative biomarkers of the gait cycle may eventually be used as control signals to drive adaptive DBS to further improve gait dysfunction in patients with Parkinsons disease.


title: Relationship between common polymorphisms of NRAMP1 gene and pulmonary tuberculosis in Lorestan LUR population

abstract:
IntroductionTuberculosis (TB) is caused by Mycobacterium tuberculosis. In humans, a number of genes have been identified as susceptible to pulmonary tuberculosis. The relationship between NRAMP1 polymorphisms and pulmonary tuberculosis has been studied in different populations and has reported contradictory results. The aim of this study was to investigate the relationship between the common polymorphisms of NRAMP1 gene and the susceptibility to pulmonary tuberculosis in the LUR Population of Lorestan province of Iran.

Materials and MethodsIn this case control study, three common polymorphisms of NRAMP1 gene (3UTR, INT4 and D543N) were genotyped using PCR-RFLP technique in the LUR population of Lorestan province. In this study, 100 patients with pulmonary tuberculosis (PTB) were studied as case group and 100 healthy controls that matched for age and sex with the patient group, studied as control group. Statistical analysis was performed using SPSS 18 software.

ResultsIn the present study we observed that the GG genotype of D543N polymorphism was statistically significantly associated with increased susceptibility to TB (84% in the case group vs. 72% in the control group, %95CI=1.024-4.071, OR=2.042, P=0.0405). Also, G allele of D543N polymorphism was statistically significantly associated with increased susceptibility to pulmonary tuberculosis (90% in the case group vs. 81.5% in the control group, %95CI=1.140-3.663, OR=2.043, P=0.015). On the other hand, the frequency of allele A of D543N polymorphism was significantly lower in patients than in the control group (10% in the case group vs. 18.5% in the control group, %95CI=0.273-0.878, OR=0.489, P=0.015). Although genotypic and allelic frequency of 3UTR and INT4 polymorphisms between patients and controls showed no significant differences in the study population.

Discussion and conclusionOur observations showed that GG genotype and G allele of D543N polymorphism have a significant role in increasing the susceptibility to pulmonary tuberculosis in the LUR Population of Lorestan province. Also, allele A of D543N polymorphism has a significant effect on resistance to pulmonary tuberculosis in this population. Although there was no significant correlation between genotypes and alleles of 3UTR and INT4 polymorphisms with susceptibility to or resistance to pulmonary TB in this population. It is suggested that a larger sample size be used in future studies. It is also recommended to conduct this type of study on other ethnicities.


abstract:
TitleDescribing COVID-19 Patients During The First Two Months of Paxlovid (Nirmatrelvir/Ritonavir) Initiation in a Large HMO in Israel

ObjectiveThe objective of this feasibility study was to assess the number of patients that could be included in a future Real World Evidence study, which would be designed to explore the impact of Paxlovid (nirmatrelvir/ritonavir) on patient outcomes and healthcare resource utilization (HCRU). We also intend to assess the comparability of the patients who were treated with Paxlovid versus patients who did not receive the treatment, either because they declined any COVID-19 treatment or were diagnosed with COVID-19 prior to Paxlovid availability.

MethodsThis retrospective observational secondary data study used data from the Maccabi Healthcare Services database during the identification period of June 1, 2021, to February 28, 2022. The study population included patients with at least one positive SARS-CoV-2 RT-PCR test, or a formal rapid antigen test for SARS-CoV-2, during the identification period, the date of which also served as the COVID-19 diagnosis date. We then divided the study population into the following cohorts: Pre-Paxlovid Time Period and Paxlovid Time Period, which was further split into Paxlovid Treated and Paxlovid Untreated.

ResultsApplication of inclusion and exclusion criteria to the study population rendered 20,284 patients in the Pre-Paxlovid Time Period cohort and 5,542 in the Paxlovid Time Period cohort that were eligible to receive Paxlovid. This resulted in 3,714 in the Paxlovid Treated and 1,810 in the Paxlovid Untreated cohorts.

ConclusionsThis RWE feasibility study of patients with a positive test for COVID-19 between June 1, 2021 to February 28, 2022 illustrates potential comparability between cohorts, as described by their demographics and characteristics.


title: Clinical implementation of routine whole-genome sequencing for hospital infection control of multi-drug resistant pathogens

abstract:
BackgroundProspective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting.

Materials/methodsWe prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MSLT) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams.

ResultsOver four years (April 2017 to July 2021) 2,660 isolates were sequenced. This included MDR gram-negative bacilli (n=293 CPE, n=1309 ESBL), MRSA (n=620) and VRE (n=433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the three target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In one hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy.

ConclusionsImplementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.

SummaryWe initiated a program of routine sequencing of multi-drug resistant organisms. A custom analysis pipeline was used to automate reporting by incorporating clinical meta-data with genomics to define clusters and support infection control interventions.


title: SOFA score performs worse than age for predicting mortality in patients with COVID-19

abstract:
The use of the Sequential Organ Failure Assessment (SOFA) score, originally developed to describe disease morbidity, is commonly used to predict in-hospital mortality. During the COVID-19 pandemic, many protocols for crisis standards of care used the SOFA score to select patients to be deprioritized due to a low likelihood of survival. A prior study found that age outperformed the SOFA score for mortality prediction in patients with COVID-19, but was limited to a small cohort of intensive care unit (ICU) patients and did not address whether their findings were unique to patients with COVID-19. Moreover, it is not known how well these measures perform across races.

In this retrospective study, we compare the performance of age and SOFA scores in predicting in-hospital mortality across two cohorts: a cohort of 2,648 consecutive adult patients diagnosed with COVID-19 who were admitted to a large academic health system in the northeastern United States over a 4-month period in 2020 and a cohort of 75,601 patients admitted to one of 335 ICUs in the eICU database between 2014 and 2015.

Among the COVID-19 cohort, age (area under receiver-operating characteristic curve (AU-ROC) 0.795, 95% CI 0.762, 0.828) had a significantly better discrimination than SOFA score (AU-ROC 0.679, 95% CI 0.638, 0.721) for mortality prediction. Conversely, age (AU-ROC 0.628 95% CI 0.608, 0.628) underperformed compared to SOFA score (AU-ROC 0.735, 95% CI 0.726, 0.745) in non-COVID-19 ICU patients in the eICU database. There was no difference between Black and White COVID-19 patients in performance of either age or SOFA Score. Our findings bring into question the utility of SOFA score-based resource allocation in COVID-19 crisis standards of care.

Author SummaryThe COVID-19 pandemic has prompted hospitals to develop protocols for allocating resources if the number of patients exceed their capacity in order to save as many lives as possible. Many of these protocols use the Sequential Organ Failure Assessment (SOFA) score to identify patients who are unlikely to survive and thus should be deprioritized for care. There are concerns that the SOFA score may not accurately predict mortality in patients with COVID-19 or perform better in one racial group over another. We asked whether a simple measure, patient age, could better predict mortality than SOFA score in a group of adult patients admitted to a large academic health system in 2020. To see if any findings are unique to patients with COVID-19, we performed the same analysis in a group of adult patients taken from the eICU database, a large publicly available dataset that was collected prior to the COVID-19 pandemic. We found that age was better than SOFA score at predicting patient mortality in patients with COVID-19, but not in patients without COVID. For COVID-19, neither age or SOFA score performed better in one racial group over another. Caution is needed when applying an established disease severity index model to a new illness.

category: intensive care and critical care medicine


title: Raising the bar for patient experience during care transitions in Canada: A repeated cross-sectional survey evaluating a patient-oriented discharge summary at Ontario hospitals

abstract:
BackgroundPatient experience when transitioning home from hospital is an important quality metric linked to improved patient outcomes. We evaluated the impact of a hospital-based care transition intervention, patient-oriented discharge summary (PODS), on patient experience across Ontario acute care hospitals.

MethodsWe used a repeated cross-sectional study design to compare yearly positive responses to four questions centered on discharge communication from the Canadian Patient Experience Survey (2016-2020) among three hospital cohorts with various levels of PODS implementation. Logistic regression using a binomial likelihood accounting for site level clustering was used to assess continuous linear time trends among cohorts and cohort differences during the post-implementation period. This research had oversight from a public advisory group of patient and caregiver partners from across the province.

Results512,288 responses were included with mean age 69 {+/-} 14 years (females) and 61 {+/-} 20 years (males). Compared to non-implementation hospitals, hospitals with full implementation (>50% discharges) reported higher odds for having discussed the help needed when leaving hospital (OR=1.18, 95% CI=1.02-1.37) and having received information in writing about what symptoms to look out for (OR=1.44, 95%=1.17-1.78) post-implementation. The linear time trend was also significant when comparing hospitals with full versus no implementation for having received information in writing about what symptoms to look out for (OR=1.05, 95% CI=1.01-1.09).

InterpretationPODS implementation was associated with higher odds of positive patient experience, particularly for discharge planning. Further efforts should center on discharge management, specifically: understanding of medications and what to do if worried once home.

category: health systems and quality improvement


title: Immunogenicity and reactogenicity of a third dose of BNT162b2 vaccine for COVID-19 after a primary regimen with BBIBP-CorV or BNT162b2 vaccines in Lima, Peru.

abstract:
BackgroundThe administration of a third (booster) dose of COVID-19 vaccines in Peru initially employed the BNT162b2 (Pfizer) mRNA vaccine. The national vaccination program started with healthcare workers (HCW) who received BBIBP-CorV (Sinopharm) vaccine as primary regimen and elderly people previously immunized with BNT162b2. This study evaluated the reactogenicity and immunogenicity of the "booster" dose in these two groups in Lima, Peru.

MethodsWe conducted a prospective cohort study, recruiting participants from November to December of 2021 in Lima, Peru. We evaluated immunogenicity and reactogenicity in HCW and elderly patients previously vaccinated with either two doses of BBIBP-CorV (heterologous regimen) or BTN162b2 (homologous regimen). Immunogenicity was measured by anti-SARS-CoV-2 IgG antibody levels immediately before boosting dose and 14 days later. IgG geometric means (GM) and medians were obtained, and modeled using ANCOVA and quantile regressions.

ResultsThe GM of IgG levels increased significantly after boosting: from 28.5{+/-}5.0 AU/mL up to 486.6{+/-}1.2 AU/mL (p<0.001) which corresponds to a 17-fold increase. The heterologous vaccine regimen produced higher GM of post-booster anti-SARS-CoV-2 IgG levels, eliciting a 13% fold increase in the geometric mean ratio (95%CI: 1.02-1.27) and a median difference of 92.3 AU/ml (95%CI: 24.9-159.7). Both were safe and well tolerated. Previous COVID-19 infection was also associated with higher pre and post-booster IgG GM levels.

ConclusionAlthough both boosting regimens were highly immunogenic, two doses of BBIBP-CorV boosted with BTN162b2 produced a stronger IgG antibody response than the homologous BNT162b2 regimen in the Peruvian population. Additionally, both regimens were mildly reactogenic and well-tolerated.


title: Impact of shaggy aorta on intraoperative cerebral embolism during carotid artery stenting

abstract:
BackgroundCareful selection of patients for carotid stenting is necessary. We suggest that patients with a shaggy aorta syndrome may have a higher risk of perioperative embolic complications.

MethodsThe study is a subanalysis of the SIBERIA Trial. We included 72 patients undergoing transfemoral carotid artery stenting. All patients had an MRI DWI and a clinical neurological examination two days before and on the second and 30th days after the intervention.

Results46 patients had shaggy aorta syndrome. Intraoperative embolisms were recorded in 82.6% and 46.1% of patients with and without shaggy aorta syndrome, respectively (p=0.001). New asymptomatic ischemic brain lesions in the postoperative period occurred in 78.3% and in 26.9% of patients with and without shaggy aorta syndrome, respectively (p=0.000). 3 (6.5%) cases of stroke within 30 days after the procedure were observed only in patients with shaggy aorta syndrome. Shaggy aorta syndrome (OR 5.54 [1.83:16.7], p=0.001) and aortic arch ulceration (OR 6.67 [1.19: 37.3], p = 0.02) were independently associated with cerebral embolism. Shaggy aorta syndrome (OR 9.77 [3.14-30.37], p=0.000) and aortic arch ulceration (OR 12.9 [2.3: 72.8], p = 0.003) were independently associated with ipsilateral new asymptomatic ischemic brain lesions.

ConclusionsShaggy aorta syndrome and aortic arch ulceration significantly increase the odds of intraoperative embolism and new asymptomatic ischemic brain lesions. Carotid endarterectomy or transcervical carotid stent should be selected in the presence of aortic ulceration.

category: cardiovascular medicine


title: An Early Return-to-Work Program for COVID-19 Close Contacts in Healthcare During the Omicron Wave in Japan

abstract: During the coronavirus disease 2019 (COVID-19) pandemic, maintaining adequate staffing in healthcare facilities is important to provide a safe work environment for healthcare workers (HCWs). Japans early return-to-work (RTW) program may be a rational strategy at a time when there is an increased demand for the services of HCWs. We assessed whether the early RTW program for HCWs who have been in close contact with a COVID-19 case in our hospital was justified. Close contacts were identified according to the guidance of the World Health Organization. Between January and March 2022, 256 HCWs were identified as close contacts (median age, 35 years; 192 female). Thirty-seven (14%) secondary attack cases of COVID-19 were detected. Among 141 HCWs who applied to the early RTW program, nurses and doctors comprised about three-quarters of participants, with a higher participation rate by doctors (78%) than nurses (59%). Eighteen HCWs tested positive for COVID-19 by the sixth day after starting the early RTW program. No COVID-19 infection clusters were reported during the observation period. These findings suggest that the early RTW program for COVID-19 close contacts was a reasonable strategy for HCWs during the Omicron wave.


title: The global randomization test: A Mendelian randomization falsification test for the exclusion restriction assumption

abstract: Mendelian randomization may give biased causal estimates if the instrument affects the outcome not solely via the exposure of interest (violating the exclusion restriction assumption). We demonstrate use of a global randomization test as a falsification test for the exclusion restriction assumption. Using simulations, we explored the statistical power of the randomization test to detect an association between a genetic instrument and a covariate set due to a) selection bias or b) horizontal pleiotropy, compared to three approaches examining associations with individual covariates: i) Bonferroni correction for the number of covariates, and ii) correction for the effective number of independent covariates and iii) an r2 permutation-based approach. We conducted proof-of-principle analyses in UK Biobank, using CRP as the exposure and coronary heart disease (CHD) as the outcome. In simulations, power of the randomization test was higher than the other approaches for detecting selection bias when the correlation between the covariates was low (R2< 0.1), and at least as powerful as the other approaches across all simulated horizontal pleiotropy scenarios. In our applied example, we found strong evidence of selection bias using all approaches (e.g., global randomization test p<0.002). We identified 51 of the 58 CRP genetic variants as horizontally pleiotropic, and estimated effects of CRP on CHD attenuated somewhat to the null when excluding these from the genetic risk score (OR=0.956 [95% CI: 0.918, 0.996] versus 0.970 [95% CI: 0.900, 1.046] per 1-unit higher log CRP levels). The global randomization test can be a useful addition to the MR researcher s toolkit.


title: Psychological interventions for adult PTSD: A network and pairwise meta-analysis of short and long-term efficacy, acceptability and trial quality

abstract: While dozens of randomized controlled trials (RCTs) have examined psychological interventions for adult posttraumatic stress disorder (PTSD), no network meta-analysis has comprehensively integrated their results for all interventions and both short and long-term efficacy. We conducted systematic searches in bibliographical databases to identify RCTs comparing the efficacy (standardized mean differences in PTSD severity, SMDs) and acceptability (relative risk of all-cause dropout, RR) of trauma-focused cognitive behaviour therapy (TF-CBT), Eye Movement Desensitization and Reprocessing (EMDR), other trauma-focused psychological interventions (other-TF-PIs) and non-trauma-focused psychological interventions (non-TF-PIs) compared to each other or to passive or active control conditions. Hundred-fifty RCTs met inclusion criteria comprising 11,282, 4,443 and 3,167 patients at post-treatment assessment, [≤] 5 months follow-up and > 5 months follow-up, respectively. By far the most data exist for TF-CBT. We performed random effects network meta-analyses (efficacy) and pairwise meta-analyses (acceptability). All therapies produced large effects compared to passive control conditions (SMDs [≥] 0.80) at post-treatment. Compared to active control conditions, TF-CBT and EMDR were moderately more effective (SMDs [≥] 0.50 < 0.80), and other-TF-PIs and non-TF-PIs were slightly more effective (SMDs [≥] 0.20 < 0.50). Interventions did not differ in their short-term efficacy, yet TF-CBT was more effective than non-TF-PIs (SMD = 0.14). Results remained robust in sensitivity and outlier-adjusted analyses. Similar results were found for long-term efficacy. Interventions also did not differ in terms of their acceptability, except for TF-CBT being associated with a slightly increased risk of dropout compared to non-TF-PIs (RR=1.34; 95% CI: 1.05-1.70). Interventions with and without trauma focus appear effective and acceptable in the treatment of adult PTSD with most certainty for TF-CBT, which, however, appears somewhat less acceptable than non-TF-PIs.


title: Characteristics of patients with positional OSA according to ethnicity and the identification of a novel phenotype - Lateral Positional Patients (Lateral PP): A MESA study

abstract:
Study ObjectivesTo investigate the characteristics of Obstructive Sleep Apnea (OSA) positional patients (PP) phenotypes among different ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA) dataset. Moreover, we hypothesized the existence of a new OSA PP phenotype we coined "Lateral PP", for whom the lateral apneas hypopnea index (AHI) is at least double the supine AHI.

MethodsFrom 2,273 adults with sleep information, we analyzed data of 1,323 subjects that slept more than 4 hours and had at least 30 minutes of sleep in both the supine and the non-supine positions. Demographics and clinical information were compared for the different PP, and ethnic groups.

Results861 (65.1%) patients had OSA and 35 (4.1%) were Lateral PP. Lateral PP patients were mainly females (62.9%), obese (31.4 median body mass index), had mild to moderate OSA (94.3%), and mostly were non-Chinese American (97.1%). Among all OSA patients, 550 (63.9%) were Supine PP, and 17.7% were supine-isolated OSA (siOSA). Supine PP and Lateral PP were present in 73.1% and 1.0% of Chinese Americans, 61.0% and 3.4% of Hispanics, 68.3% and 4.7% of White-Caucasian, and 56.2% and 5.2% of Black-African American OSA patients.

ConclusionChinese-American have the highest prevalence of Supine PP, whereas Black-African American patients lean towards less Supine PP and higher Lateral PP. Lateral PP appears as a novel OSA phenotype. However, it was found for a small group of OSA patients and thus its presence should be further validated.

Brief SummaryWe studied prevalence of obstructive sleep apnea (OSA) positional phenotypes among Black African-American, Caucasian, Hispanic, and Chinese American patients and described their demographic and polysomnographic characteristics. Despite similar levels of OSA severity in the four ethnic groups, Chinese American had a higher prevalence of Supine PP, whereas Black-African American patients were significantly less Supine PP, as compared to other ethnic groups.

In addition, we identify a novel OSA PP phenotype we named "Lateral positional patients (Lateral-PP)". These OSA patients had apnea and hypopnea events mainly in the lateral position. This was a small group of OSA patients (4.1%) that were mainly obese, female, with mild-moderate OSA, and more prevalent in Black-African American.

category: respiratory medicine


title: Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments

abstract:
We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir.

From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community; 47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis; 2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy.

Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, p=0.016.

In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes; its clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.

category: nephrology


title: Magnetic Resonance Imaging Radiomics-Based Model to Identify the Pathological Features and Lymph Node Metastasis in Rectal Cancer

abstract:
BackgroundPathological features and lymph node staging plays an important role in treatment decision-making. Yet, the preoperative accurate prediction of pathological features and lymph node metastasis (LNM) is challenging.

ObjectiveWe aimed to investigate the value of MRI-based radiomics in predicting the pathological features and lymph node metastasis in rectal cancer.

MethodsIn this prospective study, a total of 37 patients diagnosed with histologically confirmed rectal cancer who underwent pelvic 3.0T magnetic resonance imaging (MRI) were enrolled. MRI images of both the primary tumor alongside the lymph nodes and specimens were performed with a node-to-node match and labeling. The correlation analysis, least absolute shrinkage, and selection operator (LASSO) logistic regression (LR), backward stepwise LR were mainly used for radiomics feature selection and modeling. The univariate and multivariate backward stepwise LR were used for preoperative clinical predictors selection and modeling.

ResultsA total of 487 lymph nodes including 39 metastatic lymph nodes and 11 tumor deposits were harvested from 37 patients. The texture features of the primary tumors could successfully predict tumor differentiation using a well-established model (area under the curve (AUC) = 0.798). Sixty-nine matched lymph nodes were randomly divided into a training cohort (n = 39) and a validation cohort (n = 30).

Three independent risk factors were obtained from 56 texture parameters closely related to LNM. A prediction model was then successfully developed, which provided AUC values of 0.846 and 0.733 in the training and test cohort, respectively. Further, tumor deposits produced a higher radiomics score (Rad-score) compared with LNM (P = 0.042).

ConclusionThe study provides two non-invasive and quantitative methods, which respectively predict the tumor differentiation and regional LNM for rectal cancer preoperatively. Ultimately, these are favorable when producing treatment protocols for rectal cancer patients.


title: Mendelian Randomization Analysis of the Relationship Between Native American Ancestry and Gallbladder Cancer Risk

abstract:
BackgroundA strong association between the proportion of Native American ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest Native American people in Chile. We set out to investigate the causal association between Native American Mapuche ancestry and GBC risk, and the possible mediating effects of gallstone disease and body mass index (BMI) on this association.

MethodsMarkers of Mapuche ancestry were selected based on the informativeness for assignment measure and then used as instrumental variables in two-sample mendelian randomization (MR) analyses and complementary sensitivity analyses.

ResultWe found evidence of a causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% for every 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.6x10-5). Mapuche ancestry was also causally linked to gallstone disease (IVW risk increase of 3.6% per 1% increase in Mapuche proportion, 95% CI 3.1% to 4.0%, p = 1.0x10-59), suggesting a mediating effect of gallstones in the relationship between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative causal effect on BMI (IVW estimate -0.006 kg/m2 per 1% increase in Mapuche proportion, 95% CI -0.009 to -0.003, p = 4.4x10-5).

ConclusionsThe results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between Mapuche ancestry and GBC risk previously noted in observational studies appears to be causal, primary and secondary prevention strategies that take into account the individual proportion of Mapuche ancestry could be particularly efficient.


title: Genotyping and population structure of the China Kadoorie Biobank

abstract: China Kadoorie Biobank is a population-based prospective cohort of >512,000 adults recruited in 2004-2008 from 10 geographically diverse regions across China. Detailed data from questionnaire and physical measurements were collected at baseline, with additional measurements at three resurveys involving approximately 5% of surviving participants. Incident disease events are captured through electronic linkage to death and disease registries and to the national health insurance system. Genome-wide genotyping has been conducted for >100,000 participants using custom-designed Axiom(R) arrays. Analysis of these data reveals extensive relatedness within the CKB cohort, signatures of recent consanguinity, and principal component signatures reflecting large-scale population movements from recent Chinese history. In addition to numerous CKB studies of candidate drug targets and disease risk factors, CKB has made substantial contributions to many international genetics consortia. Collected biosamples are now being used for high-throughput  omics assays which, together with planned whole genome sequencing, will continue to enhance the scientific value of this biobank.


title: SARS-CoV-2 outbreaks in secondary school settings in the Netherlands during fall 2020; silent circulation

abstract:
BackgroundIn fall 2020 when schools in the Netherlands operated under a limited set of COVID-19 measures, we conducted outbreaks studies in four secondary schools to gain insight in the level of school transmission and the role of SARS-CoV-2 transmission via air and surfaces.

MethodsOutbreak studies were performed between 11 November and 15 December 2020 when the wild-type variant of SARS-CoV-2 was dominant. Clusters of SARS-CoV-2 infections within schools were identified through a prospective school surveillance study. All school contacts of cluster cases, irrespective of symptoms, were invited for PCR testing twice within 48 hrs and 4-7 days later. Combined NTS and saliva samples were collected at each time point along with data on recent exposure and symptoms. Surface and active air samples were collected in the school environment. All samples were PCR-tested and sequenced when possible.

ResultsOut of 263 sampled school contacts, 24 tested SARS-CoV-2 positive (secondary attack rate 9.1%), of which 62% remained asymptomatic and 42% had a weakly positive test result. Phylogenetic analysis on 12 subjects from 2 schools indicated a cluster of 8 and 2 secondary cases, respectively, but also other distinct strains within outbreaks. Of 51 collected air and 53 surface samples, none were SARS-CoV-2 positive.

ConclusionOur study confirmed within school SARS-CoV-2 transmission and substantial silent circulation, but also multiple introductions in some cases. Absence of air or surface contamination suggests environmental contamination is not widespread during school outbreaks.


title: The changing epidemiology of shigellosis in Australia, 2001-2019

abstract:
Shigellosis is an increasing cause of gastroenteritis in Australia, including prolonged outbreaks in remote Aboriginal and Torres Strait Islander (hereafter "First Nations") communities and among men who have sex with men (MSM) in major cities. To determine associations between Shigella species and demographic and geographic factors we used negative binomial regression to analyse national case notifications of shigellosis from 2001 to 2019.

S. sonnei and S. flexneri accounted for 42% and 29% of cases, respectively. Nationally, notification rates increased from 2001 to 2019 with yearly incidence rate ratios of 1.04 (95% CI 1.02-1.07) for S. boydii, 1.05 (95% CI 1.04-1.06) for S. sonnei and 1.04 (95% CI 1.04-1.06) for S. flexneri. Children aged 0-4 years had the highest burden of infection for S. flexneri, S. sonnei and S. boydii; and males had a higher notification rate for S. sonnei (incidence rate ratio 1.24, 95% CI 1.15-1.33), reflecting transmission among MSM. First Nations Australians were disproportionately affected by shigellosis, with the notification rate in this population peaking in 2018 at 92.1 cases per 100,000. The findings of this study provide important insights into the epidemiological characteristics of shigellosis in Australia, and can be used to inform targeted public health prevention and control strategies.


title: Mortality during inpatient admissions for Takotsubo cardiomyopathy: can mortality be predicted with a scoring system?

abstract:
IntroductionThis study aims to identify which comorbidities and demographic characteristics increase the inpatient mortality rate of patients with TCM and to establish a simple scoring system to help identify those at high risk for mortality.

MethodsA retrospective cross-sectional study using the Nationwide Inpatient Sample was conducted. Admissions with and without inpatient mortality were then compared. Univariate analyses were conducted to compare admission characteristics with and without inpatient mortality. A logistic regression analysis was conducted with inpatient mortality as the dependent variability and various admission characteristics as the independent variables in order to develop a model to predict inpatient mortality. The model was then used to calculate a score, the TCM mortality score, for each admission. A receiver operator curve analysis was conducted to determine the sensitivity, specificity, negative predictive value, and positive predictive value of the TCM mortality score in prediction of inpatient mortality.

ResultsA total of 19,454 admissions were included in the final analyses. Inpatient mortality was greater in patients that were older, males, Hispanics or Asian Pacific Islanders, and those with Medicare/Medicaid. In regards to comorbidities, inpatient mortality was greater in those with heart failure, arrhythmia, and acute kidney injury. Those with mortality were also more likely to have had an intra-aortic balloon pump or having had to be placed on extracorporeal membrane oxygenation. A mortality score was found to be 4.4 in the mortality group as compared to 1.6 for those in the non-mortality group.

ConclusionInpatient mortality with Takotsubo cardiomyopathy is approximately 4.0% and those presenting with certain demographic characteristics and comorbidities are at an increased risk for mortality. A simple scoring system can help identify those at high risk for mortality.


title: Validation of a Multi-Ancestry Polygenic Risk Score and Age-Specific Risks of Prostate Cancer: A Meta-analysis Within Diverse Populations

abstract:
BackgroundWe recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program (MVP) and additional independent studies.

MethodsWithin each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population.

ResultsThe PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8,794 cases, 55,657 controls), and Hispanic (1,082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer OR was increased 3.8-fold in European ancestry men (95% CI=3.62-3.96), 2.8-fold in African ancestry men (95% CI=2.59-3.03), and 3.2-fold in Hispanic men (95% CI=2.64-3.92). The PRS did not discriminate risk of aggressive versus non-aggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: [≤]55 years, OR=7.11; 55-60 years, OR=4.26; >70 years, OR=2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk [~]10 years younger than men in the 40-60% PRS category.

ConclusionsOur findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine if the PRS could be used for risk-stratified screening and early detection.

FundingThis work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.


title: Population-based Oral Cancer Service Screening Disrupted by COVID-19 Pandemic: Observational and Simulation Study

abstract:
BackgroundIt is important for understanding the impact of COVID-19 pandemic on the missing opportunity for the early detection of oral cancer. This study aimed to assess the impact of COVID-19 pandemic on the existing population-based oral cancer (OC) service screening program in Taiwan.

MethodsBefore and after COVID-19 pandemic design was used to assess the impact of COVID-19 on the reduction of screening rate, referral rate, and the effectiveness of this OC service screening. Data and analysis after pandemic covered non-VOC period in 2020 and VOC period in 2021 compared to the historical control before pandemic in 2019.

ResultsThe screening rate decreased substantially from 26.6% before COVID-19 in 2019 to 16.7% in 2020 and 15.3% in 2021 after pandemic. The reduction of screening rate varied with months, being the most remarkable decline in March (RR=0.61, 95% CI (0.60-0.62)) and June (RR=0.09, 95% CI (0.09-0.10)) in 2021 compared with January. The referral rate was stable at 81.5% in 2020 but it was reduced to 73.1% in 2021. The reduction of screening and referral rate led to the attenuation of effectiveness of advance cancer and mortality attenuated by 4% and 5%, respectively.

ConclusionCOVID-19 pandemic disrupted the screening and the referral rate and further led to statistically significant reduction in effectiveness for preventing advanced cancer and death. Appropriate prioritized strategies must be adopted to ameliorate malignant transformation and tumor upstaging due to deference from participation in the screening.

FundingThis study was financially supported by Health Promotion Administration of the Ministry of Health and Welfare of Taiwan (A1091116).


title: Immunogenicity of BNT162b2 Vaccine Booster Dose in Patients with Inflammatory Bowel Disease Receiving Infliximab Combination Therapy: A Prospective Observational Study

abstract:
IntroductionFew data exist regarding the immunogenicity of third dose of BNT162b2 relative to second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy.

MethodsThis is prospective single center observational study conducted between January 1st, 2022 until February 28th, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine and have received two or three-dose of BNT162b2 vaccine. Patients were excluded if they were infected or had symptoms of SARS-CoV-2 previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40-45 weeks from the first dose of BNT162b2 in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated.

Results162 patients with IBD and receiving infliximab combination therapy were recruited and the number of patients in each group was 81. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/mL (43, 192)] compared to patients who received the third booster dose [207 BAU/mL (181, 234)] (p = 0.003). Neutralizing antibody levels were also lower after the second dose [80 BAU/mL (21, 95)] compared to patients who received the third booster dose [96 BAU/mL (93, 99)] (p = <0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was higher (96.3%) than those in second dose group (90%)(p = 0.026). Percentage of patients who received third (booster) dose and achieved positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was lower (88.9%) in patients who received second dose only (p=0.009).

ConclusionMost patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40-45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received 2 doses only compared to patients who received a third dose.

category: gastroenterology


title: Attention Deficit Hyperactivity Disorder Symptoms and Brain Morphology: Examining Confounding Bias

abstract:
BackgroundAssociations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for IQ, which is typically corrected for but plays an unclear role (aim 2).

MethodsParticipants were 10-year-old children from the Adolescent Brain Cognitive Development (N=7,961) and Generation R (N=2,531) studies. Cortical area and volume were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.

ResultsADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes were further reduced when including IQ (aim 2), however, we argue that adjustments could have introduced bias (e.g., by conditioning on a collider).

ConclusionsCareful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.

FundingAuthors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.


title: Solid fuel use in relation to dementia risk in middle-aged and older adults: A prospective cohort study

abstract:
ObjectivesIt remains unknown whether household air pollution is associated with dementia risk. This study examined the associations between solid fuel use for cooking and heating (the main source of household air pollution) and dementia risk.

MethodsThis analysis included data on 11,352 participants (aged 45+ years) from the 2011 wave of China Health and Retirement Longitudinal Study, with follow-up to 2018. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM) and then standardized for analysis. Household fuel types of cooking and heating were categorized as solid (e.g., coal, crop residue) and clean (e.g., central heating, solar). Multivariable analyses were performed using generalized estimating equations. Moreover, we examined the joint associations of solid fuel use for cooking and heating with the BDRM score.

ResultsWe found an independent and significant association of solid (vs. clean) fuel use for cooking and heating with a higher BDRM score after adjusting for potential confounders (e.g., {beta} = 0.14 for solid fuel for cooking; 95% CI: 0.12, 0.17). Participants who used solid (vs. clean) fuel for both cooking and heating had the highest BDRM score ({beta} = 0.20; 95%CI: 0.16, 0.23). Subgroup analysis suggested stronger associations in participants living in rural areas.

ConclusionsSolid fuel use for cooking and heating was independently associated with increased dementia risk in Chinese middle-aged and older adults, particularly among those living in rural areas. Our findings call for more efforts to facilitate universal access to clean energy for dementia prevention.


title: Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2D6/CYP2C19 genes play a role? A UK population-based study.

abstract:
BackgroundDyslipidaemia is an important risk factor for cardiovascular morbidity in people with severe mental illness and which contributes to premature mortality in this population. The link between antipsychotics and dyslipidaemia is well-established, whilst evidence on antidepressants is mixed.

AimsTo investigate (1) if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants, and (2) if CYP2D6 and CYP2C19 genetic variation plays a role.

MethodsReview of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein (L/HDL-C) cholesterol and triglycerides derived from blood samples. CYP2D6 and CYP2C19 metabolic phenotypes were assigned from genetic data. Linear regression investigated study aims.

ResultsOf 469,739 participants, 36,043 took antidepressants and 3,255 antipsychotics. Significant associations were found between use of amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine, and venlafaxine with worse levels of each lipid parameter (i.e., higher total cholesterol, LDL-C, and triglycerides and lower HDL-C). Venlafaxine was associated with the worst lipid profile (total cholesterol, mean difference: 0{middle dot}21 mmol/L, 95% confidence interval [CI]: 0{middle dot}17 to 0{middle dot}26, p<0{middle dot}001). Antipsychotic use was associated with lower HDL-C and higher triglycerides (0{middle dot}31 mmol/L, 95% CI 0{middle dot}28 to 0{middle dot}35, p<0{middle dot}001). In participants taking sertraline, the CYP2C19 intermediate metaboliser phenotype was associated with higher HDL-C (0{middle dot}05 mmol/L 95% CI: 0{middle dot}01 to 0{middle dot}09, p=0{middle dot}007) and lower triglycerides (-0{middle dot}17 mmol/L 95% CI: -0{middle dot}29 to -0{middle dot}05, p=0{middle dot}007).

ConclusionsAntidepressants are significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring of lipids. Further research should investigate why the CYP2C19 intermediate metaboliser phenotype may be protective for HDL-C and triglycerides in people taking sertraline.


title: Accident and emergency (AE) attendance in England following infection with SARS-CoV-2 Omicron or Delta

abstract:
The SARS-CoV-2 Omicron variant is increasing in prevalence around the world. Accurate estimation of disease severity associated with Omicron is critical for pandemic planning. We found lower risk of accident and emergency (AE) attendance following SARS-CoV-2 infection with Omicron compared to Delta (HR: 0.39 (95% CI: 0.30 - 0.51; P<.0001). For AE attendances that lead to hospital admission, Omicron was associated with an 85% lower hazard compared with Delta (HR: 0.14 (95% CI: 0.09 - 0.24; P<.0001)).

Conflicts of InterestsNothing to declare.

Funding statementThis work was supported by the Medical Research Council MR/V015737/1. TPP provided technical expertise and infrastructure within their data centre pro bono in the context of a national emergency. Rosalind Eggo is funded by HDR UK (grant: MR/S003975/1), MRC (grant: MC_PC 19065), NIHR (grant: NIHR200908).


title: Effect of Digoxin on Interstage Outcomes following Stage I Palliation for Functionally Univentricular Hearts: A Systematic Review and Meta-Analysis

abstract:
ObjectivesThe goal of this systematic review and meta-analysis is to investigate the effects of digoxin on outcomes following stage I palliation for functionally univentricular hearts.

Data SourcesWe conducted electronic searches of PubMed, Ovid and Cochrane.

Study SelectionInclusion criteria included publication dates 1970-2018, children with functionally univentricular hearts between stage I and stage II palliation who received digoxin were compared to those who did not.

Data ExtractionWe identified 148 unique citations; 5 full-text articles were included in the final review. Data from 4 studies was pooled for meta-analysis.

Data SynthesisA total of 4 studies with 1,498 patients were included in the final analyses. Patient enrollment occurred between 2003 and 2013. A majority of patients were born full-term and approximately 25% were diagnosed with a syndrome. The most common cardiac diagnosis was hypoplastic left heart syndrome (70%). The most common initial surgical palliation was the Norwood procedure with a right ventricle to pulmonary artery conduit. The total amount of deaths was 121 (12 digoxin group versus 109 no digoxin group). The interstage mortality was reduced in the digoxin group [OR 0.25(95% CI 0.14 to 0.47)]. There was no statistically significant difference in the presence of arrhythmias or other complications.

ConclusionsThis systematic review and meta-analysis suggests that digoxin significantly decreases interstage period mortality with a concurrent significant decrease in weight for age. The odds of arrhythmia or other complications are not significantly different with digoxin based on current data.


title: Speed and accuracy of whole-genome nanopore sequencing for differential Neisseria gonorrhoeae strain detection in samples collected prospectively from a sexual health clinic

abstract:
BackgroundAntimicrobial resistance (AMR) in Neisseria gonorrhoeae is a continuing global health challenge. Limitations to current national surveillance systems for reporting AMR trends, alongside reduction in culture-based diagnostics and susceptibility testing, has led to an increasing need for rapid diagnostics and identification of circulating N. gonorrhoeae strains. We investigated nanopore based sequencing time and depth needed to accurately identify closely related N. gonorrhoeae isolates, compared to Illumina MiSeq sequencing.

MethodsN. gonorrhoeae strains prospectively collected from a London Sexual Health clinic were sequenced on both Illumina MiSeq and Oxford Nanopore Technologies (ONT) MinION platforms. Accuracy was determined by comparing variant calls at 68 nucleotide positions representing 37 pre-characterised resistance associated markers in N. gonorrhoeae. Accuracy at varying MinION sequencing depths were determined through retrospective analysis of time-stamped reads.

ResultsOf the 22 MinION-MiSeq sequence pairs that reached sufficient depth of coverage for comparison, overall agreement of variant call positions passing quality control criteria was 185/185 (95% CI: 98.0-100.0), 502/503 (95% CI: 98.9-99.9) and 564/565 (95% CI: 99.0-100.0) at 10x, 30x and 40x MinION depth, respectively. Isolates found to be genetically closely related by MiSeq, that is within one yearly evolutionary distance of [≤]5 single nucleotide polymorphisms, were accurately identified as such via MinION.

ConclusionNanopore based sequencing shows utility for use as a rapid surveillance tool to correctly detect closely related N. gonorrhoeae strains, with just 10x sequencing depth, taking a median sequencing time of 29 minutes. This highlights its potential utility for tracking local gonorrhoea transmission and AMR markers.

category: sexual and reproductive health


title: Longitudinal analyses of depression and anxiety highlight greater prevalence during COVID-19 lockdowns in the Dutch general population and a continuing increase in suicidal ideation in young adults

abstract:
ObjectiveThe pandemic of the coronavirus disease 2019 (COVID-19) has led to an increased burden on mental health. This study therefore investigated the development of major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidal ideation in the Netherlands during the first fifteen months of the pandemic and three nation-wide lockdowns.

MethodsParticipants of the Lifelines Cohort Study -a Dutch population-based sample-reported current symptoms of MDD and GAD, including suicidal ideation, according to DSM-IV criteria using a digital structured questionnaire. Between March 2020 and June 2021, 36,106 participants (aged 18-96) filled out a total of 629,811 questionnaires across 23 time points. Trajectories over time were estimated using generalized additive models and analyzed in relation to age, sex, and lifetime history of MDD/GAD to identify groups at risk.

ResultsWe found non-linear trajectories for MDD and GAD with a higher number of symptoms and prevalence rates during periods of lockdown. The point prevalence of MDD and GAD peaked during the third hard lockdown at 2.88% (95% CI: 2.71%-3.06%) and 2.92% (95% CI: 2.76%-3.08%), respectively, in March 2021. Women, younger adults, and participants with a history of MDD/GAD reported significantly more symptoms. For suicidal ideation, we found a linear increase over time in younger participants which continued even after the lockdowns ended. For example, 4.63% (95% CI: 3.09%-6.96%) of 20-year-old participants reported suicidal ideation at our last measured time point in June 2021, which represents a 4.14x increase since the start of the pandemic.

ConclusionsOur study showed greater prevalence of MDD and GAD during COVID-19 lockdowns suggesting that the pandemic and government enacted restrictions impacted mental health in the population. We furthermore found a continuing increase in suicidal ideation in young adults. This warrants for alertness in clinical practice and prioritization of mental health in public health policy.