title: ASSOCIATION BETWEEN NUTRITIONAL STATE AND PHASE ANGLE IN SYMPTOMATIC AND ASYMPTOMATIC HTLV-1 INFECTED PATIENTS

abstract:
IntroductionThe nutritional status of symptomatic and asymptomatic human T-cell lymphotropic virus type 1 (HTLV-1) infected patients is understudied. The phase angle (PA) has been described in the scientific literature as a prognostic indicator of nutritional status, but this has not been sufficiently discussed in the literature. Therefore, neither the impact of the infection nor the diseases progression is sufficiently known regarding the nutritional status, body condition or composition.

ObjectiveTo compare the nutritional status of symptomatic and asymptomatic adult individuals infected by HTLV-1, using the PA and anthropometric measures as a prognostic indicator in the HTLV-1 infected population.

MethodologyThis was an observational, cross-sectional study with symptomatic and asymptomatic HTLV-1 patients followed up at the Neurology outpatient clinic of the Evandro Chagas National Institute of Infectious Diseases (INI-FIOCRUZ), Brazil, from September 2015 to September 2019. Anthropometric measures and indices (body weight, height, body mass index-BMI, mid-upper arm circumference-MUAC, triceps skinfold - TSF, and mid- arm muscle circumference-MUAC), and bioimpedance (phase angle-PA, percentage of lean mass-%LM, and percentage of fat mass-%FM) were checked to assess the nutritional status. Anthropometric variables were classified according to reference values and compared between groups (symptomatic and asymptomatic). Individuals were considered malnourished when at least one of the nutritional assessment results was outside the reference values. PA was correlated with the nutritional status, and groups of symptomatic and asymptomatic were compared to each other. The R-project(R) program version 3.0.2 was used to analyze the data. Differences were considered significant when the p-value was [≤] 0.05.

ResultsNinety-one patients were evaluated, 33 (36.3%) asymptomatic and 58 (63.7%) symptomatic. The majority were female (61.5%) and the median age was 60 (55-58) years. Symptomatic participants, compared to asymptomatic, had a lower proportion of overweight/obesity (51.7% vs 78.8%; p =0.0171), lower BMI (25.47 {+/-} 5.06 kg/m2 vs 30.08 {+/-} 5.61 kg/m2; p = <0.001), MUAC (29.56 {+/-} 5.13 cm vs 33.22 {+/-} 4.21 cm; p =0.0011), and %FM (30.75% vs 36.60%; p =0.0064), however, had a higher %LM (68.95% vs 63.40%; p =0.0299). All participants presented PA, however there was no difference between symptomatic (5.74{o} {+/-} 1.18) and asymptomatic (6.21{o} {+/-} 1.16).

ConclusionOverweight and obesity were prevalent, especially among asymptomatic participants. Symptomatic participants had lower BMI, MUAC and %FM. Mid-upper arm circumference was considered a good parameter for monitoring the nutritional status of people with HTLV, mainly in situations where weight measurement is not viable. PA was altered in both groups, therefore, it cannot be used as a disease progression indicator, but it does indicate that HTLV infection alone should be a risk of cellular membrane integrity damage. Studies using PA assessment in HTLV-1 carriers are needed.

AUTHORS SUMMARYHTLV is a disease very little explored, and in the scientific field of nutrition it is no different, we found few studies that associate this population and their nutritional status. In academic literature we can find the association of weight, height and BMI, rare studies with bioimpedance assessments.

Until this moment, no study has associated nutritional status with the phase angle, which is being used in several infectious diseases as a prognostic indicator of cell membrane integrity.

In this study, we note that even though the phase angle values are not significant, they show that, regardless of the symptoms, patients who are infected with the HTLV virus are already considered to have damage to the membrane integrity, which makes us emphasize the importance of new studies to a better understanding of factors related to weight gain and probable nutritional deficiencies.


title: Acupuncture with or without acupoint application for primary dysmenorrhea: protocol for a systematic review and meta-analysis

abstract:
IntroductionDysmenorrhea is the most common gynaecological symptom reported by women. Ninety percent of women presenting for primary care experience some menstrual pain. Population surveys suggest that, although prevalence rates vary considerably by geographic al location, complaints of dysmenorrhea are widespread in diverse populations. This study will evaluate the results of randomized controlled trials to determine the efficacy and safety of acupuncture with or without acupoint application for the treatment of dysmenorrhea.

MethodsEight databases, including China National Knowledge Infrastructure, Chinese Scientific Journal Database, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PubMed, Wanfang Database, and Web of Science, will be searched using English and Chinese search strategies. In addition, manual retrieval of research papers, conference papers, ongoing experiments, and internal reports, among others, will supplement electronic retrieval. All eligible studies published on or before December 12, 2021 will be selected. To enhance the effectiveness of the study, only clinical randomized controlled trials related to the use of acupuncture with or without acupoint application for the treatment of dysmenorrhea will be included.

AnalysisThe Visual Analog Scale will be the primary outcome measure, whereas the McGill pain questionnaire, SF-36 Scale, Self-Rating Anxiety, and Self-Rating Depression scale will be the secondary outcomes. Side effects and adverse events will be included as safety evaluations. To ensure the quality of the systematic evaluation, study selection, data extraction, and quality assessment will be independently performed by two authors, and a third author will resolve any disagreement.

Ethics and disseminationThis systematic review will evaluate the efficacy and safety of acupuncture with or without acupoint application for the treatment of dysmenorrhea. Since all included data will be obtained from published articles, it does not require ethical approval and will be published in a peer-reviewed journal.

INPLASY registration numberINPLASY202230051.

category: public and global health


title: Neutrophils in severe COVID-19 are characterized by a hyperactive immature state and maintained CXCR2 expression

abstract: Neutrophils are vital in defence against pathogens but excessive neutrophil activity can lead to tissue damage and promote acute respiratory distress syndrome (ARDS). COVID-19 is associated with systemic expansion of immature neutrophils but the functional consequences of this shift to immaturity are not understood. We used flow cytometry to investigate activity and phenotypic diversity of circulating neutrophils in COVID-19. First, we demonstrate hyperactivation of immature CD10- subpopulations in severe disease, with elevated degranulation of secondary granule markers. Partially activated immature neutrophils are detectable three months post symptom onset, indication long term myeloid dysregulation in convalescent COVID-19 patients. Second, we demonstrate that neutrophils from moderately ill patients downregulate the chemokine receptor CXCR2, while neutrophils from severely ill individuals failed to do so, suggesting altered ability for organ trafficking. CD10- and CXCR2hi neutrophil subpopulations were enriched in severe disease and may represent biomarkers for early identification of individuals at high risk of progressing to severe COVID-19.

category: allergy and immunology


title: Hyperactive immature state and differential CXCR2 expression of neutrophils in severe COVID-19


title: Adherence to 24h movement recommendations and health indicators in the ABCD study: Cross-sectional and longitudinal associations with cognition, psychosocial health, BMI and brain structure

abstract: Adherence to 24h movement guidelines of [≥]60min of physical activity, [≤]2h of screen time, and 9-11h of sleep has been shown to benefit cognition, physical and psychosocial health in children aged 5-13y. However, these findings are largely based on cross-sectional studies or small samples. Here we utilize data from the Adolescent Brain Cognitive Development (ABCD) study of 10000+ children aged 9-11y to examine whether adherence to 24h movement guidelines benefit cognition, BMI, psychosocial health and brain morphometric measures at baseline (T1) and 2 years later (T2). After adjustment for sociodemographic confounders in multivariable linear mixed models, we observed better cognitive scores, fewer behavioural problems, lower adiposity levels and greater gray matter volumes in children who met both sleep and screen time recommendations compared to those who met none. Longitudinal follow up further supports these findings; participants who met both recommendations at T1 and T2 evidenced better outcome measures than those who met none, even after controlling for T1 measures. These findings support consideration of integrated rather than isolated movement recommendations across the day for better cognitive, physical, psychosocial and brain health.

category: pediatrics


title: The brain mechanisms of self-identification & self-location in neurosurgical patients using virtual reality and lesion network mapping

abstract:
Background and ObjectivesThe identification of cognitive biomarkers in preoperative counselling and their monitoring during brain surgery is of growing interest for the safe conduction of resective intracranial procedures with potential impact on the patients personality. The conscious experience of identifying with the body (self-identification) and of where  I am in space(self-location) are central for bodily self-consciousness (BSC). In a virtual reality (VR) paradigm using multisensory feedback, illusory self-identification and self-location over a virtual body can be induced, by manipulating the synchrony of visuo-tactile inputs. To date, no studies applied lesion network mapping (LNM) to investigate networks underlying BSC components with VR.

MethodsFifteen neurosurgical patients with intra-axial and extra-axial brain lesions(8 pre-resection, 9 post-resection) performed the visuo-tactile VR paradigm. Patients subjectively rated their self-identification and self-location, after being exposed to synchronous or asynchronous visuo-tactile stimulations. We applied LNM analysis using functional data from 1015 healthy subjects and determined functional connectivity patterns related to each measure.

ResultsIn the post-surgery group, the self-identification network included the right inferior frontal, superior frontal and inferior temporal gyri. The self-location network encompassed the right parahippocampal gyrus, superior temporal gyrus, bilateral cerebellum and brainstem. No clusters survived for the pre-surgery group.

DiscussionOur LNM findings reveal the existence of two distinct networks for self-identification and self-location, including structures playing key roles in self-recognition or self-other distinction as well as in spatial navigation or memory processes, respectively. Such networks should be added to the portfolio of presurgical surveillance of functions related to the sense of self to improve future surgical outcomes.

What is already known on this topicThe development of extra- and intraoperative cognitive biomarkers is of importance for monitoring the personality of patients during cranial surgical procedures, as that may allow for individualized pre-operative counselling and intraoperative decision making. Such guidance may ultimately help to improve neuropsychological outcomes following brain surgery.

Bodily self-consciousness refers to a perceptual form of the sense of self, related to multisensory bodily inputs, which can be disrupted in neurological, psychiatric, or neurosurgical conditions.

What this study addsIn this study, we investigated networks associated with changes in two components bodily self-consciousness (self-identification, self-location) that we manipulated in real-time using multisensory stimulation and virtual reality in neurosurgical patients, who underwent resective surgery for brain tumors or lesions (gliomas, meningiomas, epileptic foci).

Our lesion network mapping findings reveal the existence of two distinct networks of bodily self-consciousness, including structures playing key roles in self-recognition or self-other distinction for self-identification, and in spatial navigation or memory processes for self-location.

How this study might affect research, practice or policyIdeally, such networks should be identified, and their individual anatomical allocation be integrated in the surgical plan, to make them potentially amenable for functional mapping and monitoring during resective brain surgery. Ultimately, that assessment of functions related to the sense of self and personality should help.

category: neurology


title: The contribution of white matter pathology, hypoperfusion, lesion load, and stroke recurrence to language deficits following acute subcortical left hemisphere stroke

abstract: Aphasia, the loss of language ability following damage to the brain, is among the most disabling and common consequences of stroke. Subcortical stroke, occurring in the basal ganglia, thalamus, and/or deep white matter can result in aphasia, often characterized by word fluency, motor speech output, or sentence generation impairments. The link between greater lesion volume and acute aphasia is well documented, but the independent contributions of lesion location, cortical hypoperfusion, prior stroke, and white matter degeneration (leukoaraiosis) remain unclear, particularly in subcortical aphasia. Thus, we aimed to disentangle the contributions of each factor on language impairments in left hemisphere acute subcortical stroke survivors. Eighty patients with acute left hemisphere subcortical stroke (less than 10 days post-onset) participated. We manually traced acute lesions on diffusion-weighted scans and prior lesions on T2-weighted scans. Leukoaraiosis was rated on T2-weighted scans using the Fazekas et al. (1987) scale. Fluid-attenuated inversion recovery (FLAIR) scans were evaluated for hyperintense vessels in each vascular territory, providing an indirect measure of hypoperfusion in lieu of perfusion-weighted imaging. Compared to subcortical stroke patients without aphasia, patients with aphasia had greater acute and total lesion volume, were older, and had significantly greater damage to the internal capsule (which did not survive controlling for total lesion volume). Patients with aphasia did not differ from non-aphasic patients by other demographic or stroke variables. Age was the only significant predictor of aphasia status in a logistic regression model. Further examination of three participants with severe language impairments suggests that their deficits result from impairment in domain-general, rather than linguistic, processes. Given the variability in language deficits and imaging markers associated with such deficits, it seems likely that subcortical aphasia is a heterogeneous clinical syndrome with distinct causes across individuals.


title: Prediction of Uterine Dehiscence via Machine Learning by Using Lower Uterine Segment Thickness and Clinical Features

abstract:
BackgroundWith the global increase of Cesarean section delivery rates, the long-term effects of Cesarean delivery have started to become more clear. One of the most prominent complications of Cesarean section in recurrent pregnancies is uterine rupture. Assessing the risk of uterine rupture or dehiscence is very important in order to prevent untimely operations and/or maternal and fetal complications.

ObjectiveOur study aims to assess whether machine learning can be used to predict uterine dehiscence or rupture by using patients ultrasonographic findings, clinical findings and demographic data as features. Hence, possible uterine rupture, as well as maternal and fetal complications pertinent to it, could be prevented.

Study DesignThe study was conducted on 317 patients with term (>37 weeks) singleton pregnancy. Demographics, body-mass indices, smoking and drinking habits, clinical features, past pregnancies, number and history of abortions, inter-delivery period, gestation week, number of previous Cesarean operations, fetal presentation, fetal weight, tocography data, trans-abdominal ultrasonographic measurement of lower uterine segment full thickness and myometrium thickness, lower uterine segment findings during Cesarean section were collected and analyzed using machine learning techniques. Logistic Regression, Multilayer Perceptron, Support Vector Machine, Random Forest and Naive Bayes algorithms were used for classification. The dataset was evaluated using 10-fold cross-validation. Correct Classification Rate, F-score, Matthews Correlation Coefficient, Precision-Recall Curve area and Receiver Operating Characteristics area were used as performance metrics.

ResultsAmong the machine learning techniques that has been tested in this study, Naive Bayes algorithm showed the best prediction performance. Among the various combinations of features used for prediction, the essential features of parity, gravida, tocographic contraction, dilation, d&c with the sonographic thickness of lower uterine segment myometrium yielded the best results. The runner-up performance was obtained with the sonographic full thickness of lower uterine segment added to the base features. The base features alone can classify patients with 90.5% accuracy, while adding the myometrium measurement increases the classification performance by 5.1% to 95.6%. Adding the full thickness measurement to the base features raises the classification performance by 4.8% to 95.3% in terms of Correct Classification Rate.

ConclusionNaive Bayes algorithm can correctly classify uterine rupture or dehiscence with a Correct Classification Rate of 0.953, an F-score of 0.952 and a Matthews Correlation Coefficient value of 0.641. This result can be interpreted such that by using clinical features and lower uterine segment ultrasonography findings, machine learning can be used to accurately predict uterine rupture or dehiscence.

Trial registrationClinical Research Ethics Committee of Ankara City Hospital, University of Health Sciences (Approval number: E2-20-108)

Date of registration: 27-01-2021

URL: https://ankarasehir.saglik.gov.tr/TR-348810/2-nolu-etik-kurul.html

e-mail: ankarash.etikkurul2@saglik.gov.tr

AJOG at a GlanceA. Why was this study conducted?This study was conducted to:

O_LIDetermine whether machine learning algorithms can be utilized to predict uterine dehiscence and assess the risk of uterine rupture
C_LIO_LIEvaluate the contribution of ultrasonographic measurement of lower uterine segment measurements to the prediction performance of the algorithms
C_LIO_LIFind out which machine learning technique performs the best for predicting uterine dehiscence.
C_LI

B. What are the key findings?O_LIMachine learning methods can be used to accurately predict uterine dehiscence (with up to 95.6% accuracy).
C_LIO_LIUsing lower uterine segment full thickness or myometrium thickness increases the accuracy of Naive Bayes algorithm by 4.8% and 5.1%, respectively.
C_LIO_LINaive Bayes algorithm yields the best prediction performance among the methods tried.
C_LI

C. What does this study add to what is already known?O_LIUltrasonographic lower uterine segment measurements can be used as features in machine learning to increase its prediction performance of uterine dehiscence and hence the risk of uterine rupture.
C_LI

category: obstetrics and gynecology


title: Prognostic factors for mortality, ICU and hospital admission due to SARS-CoV-2: A systematic review and meta-analysis of cohort studies in Europe

abstract:
BackgroundAs mortality from COVID-19 is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations.

MethodsWe performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to SARS-CoV-2, including death, hospitalisation, Intensive Care Unit (ICU) admission, and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11th June 2021 in Ovid Medline and Embase. Results are presented as Odds Ratios (ORs) with 95% confidence intervals (95%C.I.) and absolute risk differences (RD) in deaths per 1,000 COVID-19 patients.

FindingsWe included 88 cohort studies with age/gender adjusted data from 6,653,207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease, and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes, and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke, and liver disease.

InterpretationThe results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of non-pharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.

FundingEuropean Centre for Disease Prevention and Control (ECDC) under specific contract No. 10 ECD.11843 within Framework contract ECDC/2019/001 Lot 1B.

category: infectious diseases


title: Accuracy of COVID-19 self-tests with unsupervised nasal or nasal plus oropharyngeal self-sampling in symptomatic individuals in the Omicron period

abstract:
BackgroundPerformances of rapid antigen diagnostic tests (Ag-RDTs) with nasal self-sampling, and oropharyngeal plus nasal (OP-N) self-sampling, in the Omicron period are unknown.

MethodsProspective diagnostic accuracy study among 6,497 symptomatic individuals aged >16 years presenting for SARS-CoV-2 testing at three test-sites. Participants were sampled for RT-PCR (reference test) and received one Ag-RDT to perform unsupervised with either nasal self-sampling (during the emergence of Omicron, and after Omicron share was >90%, phase-1) or with OP-N self-sampling (in a subsequent phase-2; Omicron share >99%). The evaluated tests were Acon Flowflex (Flowflex; phase-1 only), MP Biomedicals (MPBio), and Siemens-Healthineers Clinitest (Clinitest).

FindingsDuring phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for Flowflex, 69.9% (65.1-74.4%) for MPBio, and 70.2% (65.6-74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points, respectively, when transitioning from 29% to >95% Omicron. During phase-2, 53% of MPBio, and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. Comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively).

InterpretatioSensitivities of three Ag-RDTs with nasal self-sampling decreased during Omicron emergence but was only statistically significant for Clinitest. Sensitivities were substantially influenced by the proportion of confirmatory testers. Addition of oropharyngeal to nasal self-sampling improved sensitivities of MPBio and Clinitest.

FundingDutch Ministry of Health, Welfare, and Sport.

Research into contextO_ST_ABSEvidence before this studyC_ST_ABSSARS-CoV-2 rapid antigen diagnostic tests (Ag-RDTs) require no or minimal equipment, provide a result within 15-30 minutes, and can be used in a range of settings including for self-testing at home. Self-testing may potentially lower the threshold to testing and allows individuals to obtain a test result quickly and at their own convenience, which could support the early detection of infectious cases and reduce community transmission. Real world evidence on the performance of unsupervised nasal and oropharyngeal plus nasal (OP-N) self-sampling in the Omicron variant period is needed to accurately inform end-users and policymakers. Therefore, we conducted a large prospective diagnostic accuracy study of three commercially available Ag-RDTs with self-sampling (the Acon Flowflex test, the MP Biomedicals test, and the Siemens-Healthineers Clinitest) during and after the emergence of Omicron using RT-PCR as the reference standard. Our aims were to evaluate whether the accuracies of Ag-RDTs with nasal self-sampling changed over time with the emergence of Omicron; and to determine whether addition of oropharyngeal to nasal self-sampling with the same swab yielded higher diagnostic accuracies.

What this study addsThe large comprehensive study was conducted in almost 6,500 participants with symptoms when presenting for routine SARS-CoV-2 testing at three public health service COVID-19 test-sites in the Netherlands. During the study, conducted between 21 December 2021 and 10 February 2022, the percentage of the Omicron variant in samples from the national SARS-CoV-2 pathogen surveillance increased from 29% in the first week to 99% in the last week of the study. The period during which the Omicron variant was dominant was divided into a nasal sampling phase (phase-1; Omicron present in >90% of surveillance samples) and an OP-N sampling phase (phase-2; Omicron share was >99%). In phase-1, 45% of Flowflex, 29% of MPBio, and 35% of Clinitest participants visited the test-site because of a positive self-test (confirmatory testers). Overall sensitivities with nasal self-sampling were 79.0% (95% CI: 74.7-82.8%) for the Flowflex, 69.9% (65.1-74.4%) for the MPBio, and 70.2% (65.6-74.5%) for the Clinitest Ag-RDT. Sensitivities were 94%, 84%, and 86%, respectively, for confirmatory testers, and 52%, 52%, and 50%, respectively, for those who had other reasons for getting tested. Sensitivities were 87.0% (79.7-92.4%), 83.1% (72.9-90.7%), and 80.0% (51.9-95.7%), respectively, in the first week, and decreased by 6.1 (p=0.16 by Chi-square test), 7.0 (p=0.60), and 12.8 (p=0.025) percentage points in the final week of the study. In Phase-2, 53% of MPBio and 44% of Clinitest participants were confirmatory testers. Overall sensitivities with OP-N self-sampling were 83.0% (78.8%-86.7%) for MPBio and 77.3% (72.9%-81.2%) for Clinitest. When comparing OP-N to nasal sampling, sensitivities were slightly higher in confirmatory testers (87.4% and 86.1%, respectively), and substantially higher in those testing for other reasons (69.3% and 59.9%).

Implications of all the available evidenceThe sensitivities of three commercially available Ag-RDTs performed with nasal self-sampling decreased during the emergence of Omicron, but this trend was only statistically significant for Clinitest. Addition of oropharyngeal to nasal self-sampling improved the sensitivity of the MPBio and Clinitest, most notably in individuals who visited the test-site for other reasons than to confirm a positive self-test. Based on these findings, the manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal sampling, and other manufacturers may consider evaluating this as well.


title: Inverse proportionality between height and duration of epidemic peaks not observed for the COVID-19 epidemic in Japan

abstract: The height of the epidemic peaks varied ten-fold, but the duration was almost constant independent of the peak height in the six times COVID-19 epidemics in Japan over the past two years. The observed relation between the peak height and duration contradicts the inverse proportionality, which is the essential conclusion derived from mathematical models for infectious diseases. We found that the peak height was inversely proportional to the number of rhinovirus patients. The literature has revealed the mechanism behind our found power of rhinovirus suppressing COVID-19. We discuss that the critical flaw of current mathematical models originates in the absence of the 0th power term of the number of infected people in the Kermack and McKendrick equation.


title: Prediction of CRT Response Using a Lead Placement Score Derived from 4DCT

abstract:
BackgroundCardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure; however, 30% of patients do not respond to the treatment. We sought to derive patient-specific left-ventricle (LV) maps of lead placement scores (LPS) that highlight target pacing lead sites for achieving a higher probability of CRT response.

MethodsEighty-two subjects recruited for the ImagingCRT trial were retrospectively analyzed. All 82 subjects had two contrast-enhanced full-cardiac cycle 4DCT scans: a baseline and a 6-month follow-up scan. CRT response was defined as a reduction in CT-derived end-systolic volume [≥]15%. Eight LV features derived from the baseline scans were used to train a support vector machine (SVM) via a bagging approach. An LPS map over the LV was created for each subject as a linear combination of the SVM feature weights and the subjects own feature vector. Performance for distinguishing responders was performed on the original 82 subjects.

ResultsFifty-two (63%) subjects were responders. Subjects with an LPS[≤]Q1 (lower-quartile) had a posttest probability of responding of 14% (3/21), while subjects with an LPS[≥] Q3 (upper-quartile) had a posttest probability of responding of 90% (19/21). Subjects with Q1<LPS<Q3 had a posttest probability of responding that was essentially unchanged from the pretest probability (75% vs 63%, p=0.2). An LPS threshold that maximized the geometric mean of true-negative and true-positive rates identified 26/30 of the non-responders. The AUC of the ROC curve for identifying responders with an LPS threshold was 87%.

ConclusionsAn LPS map was defined using 4DCT-derived features of LV mechanics. The LPS correlated with CRT response, reclassifying 25% of the subjects into low-probability of response, 25% into high-probability of response, and 50% unchanged. These encouraging results highlight the potential utility of 4DCT in guiding patient selection for CRT. The present findings need verification in larger independent data sets and prospective trials.

Clinical PerspectiveCardiac resynchronization therapy (CRT) is a proven treatment for patients with heart failure and dyssynchrony; however, approximately 30% of patients do not respond to the treatment. Additionally, the relatively high non-responder rate poses difficulties for the optimal utilization of medical resources; thus, more accurate patient stratification for CRT remains an unmet need. Despite significant efforts focused on using imaging to guide CRT, the results thus far have been ambiguous. Poor reproducibility of echocardiography coupled with the complexity of cardiac magnetic resonance have likely contributed to the poor overall adoption of these methods for pre-CRT assessment. In this work, we describe a metric called the lead placement score (LPS) that combines multiple 4DCT-derived features of left-ventricular (LV) mechanics into a single number for each possible pacing lead location on the LV; the features included in the LPS map have previously been shown to correlate with CRT response. Using a machine learning classifier, a model was constructed with these features and then used to derive the LPS map for each individual subject. The LPS was found to correlate with the probability of a subject responding to CRT. 4DCT is widely available and provides high-resolution images of the full cardiac cycle. Additionally, recent technological advancements have also dramatically reduced the radiation dose from 4DCT scans. The advantages of 4DCT coupled with the promising results reported in this study, highlight the potential utility of 4DCT in the planning of CRT.

category: cardiovascular medicine


title: COVID-19 Vaccine Effectiveness against the Omicron BA.2 variant in England

abstract: The BA.1 sub-lineage of the Omicron (B.1.1.529) variant, first detected in the UK in mid-November 2021, rapidly became the dominant strain partly due to reduced vaccine effectiveness. An increase in a second Omicron sub-lineage BA.2 was observed in early January 2022. In this study we use a test-negative case control study design to estimate vaccine effectiveness against symptomatic disease with BA.1 and BA.2 after one or two doses of BNT162b2, ChAdOx1-S or mRNA-1273, and after booster doses of BNT162b2 or mRNA-1273 during a period of co-circulation. Overall, there was no evidence that vaccine effectiveness against symptomatic disease is reduced following infection with the BA.2 sub-lineage as compared to BA.1. Furthermore, similar rates of waning were observed after the second and booster dose for each sub-lineage. These data provide reassuring evidence of the effectiveness of the vaccines currently in use against symptomatic disease caused by BA.2.

category: epidemiology


title: Systematic review and meta-analysis of yellow fever vaccine in elderly population

abstract: We conducted a systematic review and meta-analysis to assess the risk of serious adverse events in the elderly after yellow fever vaccination compared to the non-elderly population. We searched multiple databases and grey literature and selected research without language and publication date restriction. Studies were analysed in a descriptive way, meta-analysed and expressed in terms of prevalence ratio and risk ratio with a 95% confidence interval, depending on the degree of heterogeneity found. A total of 18 studies were included, of which 10 were meta-analysed. Results obtained through the meta-analysis showed that the risk of serious adverse events after yellow fever vaccination is three times higher for elderlies when compared to non-elderly population and even five times higher for persons >70 years of age. Also, in relation adverse event type a greater risk was for viscerotropic disease associated with yellow fever vaccine up to six times higher when compared to the population under 60 years. The evidence found in this review supports that the vaccine indication in individuals over 60 years of age should be based on a careful analysis of the individual benefit-risk assessment. Results found suggest a higher risk of SAE for individuals over 70 years, especially for viscerotropic and neurotropic disease associated with YFV contraindicating the use of the YFV in this age group.


title: Estimated Incidence of Respiratory Hospitalizations Attributable to RSV Infections across Age and Socioeconomic Groups

abstract:
BackgroundSurveillance for respiratory syncytial virus (RSV) likely captures just a fraction of the burden of disease. Understanding the burden of hospitalizations and disparities between populations can help to inform upcoming RSV vaccine programs and to improve surveillance.

MethodsWe obtained monthly age-, ZIP code- and cause-specific hospitalizations in New York, New Jersey, and Washington from the US State Inpatient Databases (2005-2014). We estimated the incidence of respiratory hospitalizations attributable to RSV by age and by socioeconomic status using regression models. We compared the estimated incidence and the recorded incidence (based on ICD9-CM) of RSV hospitalizations to estimate the under-recorded rate in the different sub-populations.

ResultsThe estimated annual incidence of respiratory hospitalizations due to RSV was highest among infants <1 year of age with low socioeconomic status, (2700 per 100,000 people, 95% CrI [2600, 2900]) and were considerable in older adults that are [≥]65 years of age across socioeconomic status, ranging from 130 to 970 per 100,000 people. The incidence of hospitalization recorded as being due to RSV represented a significant undercount, particularly in adults. Only <5% of the estimated RSV hospitalizations were captured for the older adults that are [≥]65 years of age.

ConclusionsRSV causes a considerable burden of hospitalization in young children and in older adults in the U.S, with variation by socioeconomic group. Estimates of the incidence of hospitalizations due to RSV in older adults based on the recorded diagnoses likely represent an underestimate.

Key messagesO_ST_ABSWhat is already known on this topic?C_ST_ABSPrevious study suggested that the incidence of hospitalization for bronchiolitis (often caused by RSV) in infants varies greatly between communities of different socioeconomic levels. However, it is unclear whether these differences are associated with the admission criteria or the risk of RSV infection.

What this study adds?The estimated annual incidence of respiratory hospitalizations due to RSV in infants residing in low socioeconomic areas was about twice as high as the incidence in infants residing in high socioeconomic areas. In older adults, a small fraction of the hospitalizations estimated to be caused by RSV were recorded as such in the inpatient database.

How this study might affect research, practice or policy?With several vaccines and extended half-life monoclonal antibodies against RSV under active development, these estimates can help anticipate the impact of RSV prevention strategies in populations of different demographic characteristics.


title: Risk factors for SARS-CoV-2 transmission in student residences: a case-ascertained study in Leuven, Belgium from October 2020 until May 2021

abstract:
BackgroundStudent residences are at high risk for rapid COVID-transmission due to crowding and frequent close contact.

AimWe aimed to investigate the overall secondary attack rates (SAR) in student residences and to discern risk factors for higher transmission in order to improve the evidence base for screening efforts and preventive measures.

MethodsIn this retrospective case-ascertained study, we analysed data from student residences screened in Leuven, Belgium between October 2020 and May 2021, following detection of a COVID-19 case in the residence. We investigated the impact on the SAR in the living units screened of delay-time until follow-up, shared use of kitchen or sanitary facilities, presence of an external infection source and occurrence of social gatherings attended by the index case.

ResultsWe included 200 residence units, representing 2326 screened residents, of which 68 units showed secondary transmission. The overall SAR was estimated at 0.0813 (95%CI 0.0705-0.0936). Both sharing sanitary facilities (p=0.04) and social gatherings attended by the index case (p=0.033) significantly impacted SAR, which increased from 3% to 13% when both risk factors were present compared to absent.

ConclusionsWe identify risk factors which should be considered when selecting students for screening during an outbreak of COVID-19 in student residences to improve comprehensiveness and proportionality of testing. The identified risk factors improve the evidence base for preventive measures aimed at limiting social gatherings and improving ventilation of shared spaces in outbreak-prone settings. Lastly, they should be considered when designing student accommodation and other shared households.


title: Development of a Model for Differentiating PDAC from Benign Pancreatic Conditions: A Prospective Case-control Study

abstract:
Background & aimsPancreatic ductal adenocarcinoma (PDAC) continues to be a devastating disease with late diagnosis and poor overall survival, complicated by clinical presentations similar to benign pancreatic diseases. We aimed to analyse clinical parameters with the goal of developing a prediction model for differentiating suspected PDAC from benign pancreatic conditions.

Methods and resultsWe used a prospectively recruited cohort of patients with pancreatic disease (n=762) enrolled at the Barts Pancreas Tissue Bank between January 1, 2008 and September 21, 2021 to perform a case-control study examining the association of PDAC (n=340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Using a machine learning approach, candidate PDAC risk-prediction algorithms were trained on 75% of the cohort, using a subset of the predictor variables identified from a preliminary observational association study. Models were assessed on the remaining 25%. Multiple imputed datasets were used for both training and validation to accommodate for unknown data.

Age (over 55), weight loss in hypertensive patients, recent symptom of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low lymphocyte count and low serum sodium were the most important features when separating putative PDAC cases from less severe pancreatic conditions. A simple logistic regression model had the best performance with an area under the curve (AUC) of 0.88. Setting a probability threshold of 0.17 guided by the maximum F2 score, a sensitivity of 95.6% was reached in the full cohort which could lead to early detection of around 84% of the PDAC patients.

ConclusionThe resultant prediction model significantly outperformed the current UK guidelines for suspected pancreatic cancer referral and could improve detection rates of PDAC in the community. After further work this approach could lead to an easy to understand, utilisable risk score to be applied in the primary and secondary care setting for referring patients to specialist hepato-pancreatico-biliary services.

category: gastroenterology


title: Effectiveness of shared medical appointments delivered in primary care for improving health outcomes in patients with long-term conditions: a systematic review of randomised controlled trials

abstract:
BackgroundShared medical appointments (SMAs) have the potential to address interlinked challenges of limited capacity in primary healthcare and rising prevalence of patients with multiple long-term conditions (LTCs). This review aimed to examine the effectiveness of SMAs compared to one-to-one appointments in primary care at improving health outcomes and reducing demand on healthcare services.

MethodsWe searched for randomised controlled trials (RCTs) of SMAs involving patients with LTCs in primary care across six databases from 2013 and added eligible papers identified from previous relevant reviews. Data were extracted and outcomes narratively synthesised, meta-analysis was undertaken where possible.

ResultsTwenty-three unique trials were included. SMA models varied in terms of components, mode of delivery and target population. Most trials recruited patients with a single LTC, mostly commonly diabetes (n=13), although eight trials selected patients with multiple LTCs. There was substantial heterogeneity in outcome measures which we categorised into health outcomes (biomedical indicators, psychological and well-being measures), behavioural outcomes, and resource use. Meta-analysis showed that participants in SMA groups had lower diastolic blood pressure than those in usual care (d=-0.123, 95%CI = -0.22, -0.03, k=8). No statistically significant differences were found across other outcomes. Where individual studies showed significant differences (patient self-efficacy), these trended in favour of SMAs. Compared with usual care, SMAs had no significant effect on healthcare service use.

ConclusionsSMAs were at least as effective as usual care in terms of health outcomes and did not lead to increased healthcare service use in the short-term. They show some potential in improving self-efficacy which may boost self-care. To strengthen the evidence base, future studies should target standardised behavioural and health outcomes and clearly report SMA components so key behavioural ingredients can be identified. Similarly, transparent approaches to measuring costs would improve comparability between studies.

PROSPEROCRD42020173084

category: primary care research


title: Geospatial analysis reveals distinct hotspots of severe mental illness

abstract:
BackgroundThe identification of geographic variation in incidence can be an important step in the delineation of disease risk factors, but has mostly been undertaken in upper-income countries. Here, we use Electronic Health Records (EHR) from a middle-income country, Colombia, to characterize geographic variation in major mental disorders.

MethodWe leveraged geolocated EHRs of 16,295 patients at a psychiatric hospital serving the entire state of Caldas, all of whom received a primary diagnosis of bipolar disorder, schizophrenia, or major depressive disorder at their first visit. To identify the relationship between travel time and incidence of mental illness we used a zero-inflated negative binomial regression model. We used spatial scan statistics to identify clusters of patients, stratified by diagnosis and severity: mild (outpatients) or severe (inpatients).

ResultsWe observed a significant association between incidence and travel time for outpatients (N = 11,077, relative risk (RR) = 0.80, 95% confidence interval (0.71, 0.89)), but not inpatients (N = 5,218). We found seven clusters of severe mental illness: the cluster with the most extreme overrepresentation of bipolar disorder (RR = 5.83, p < 0.001) has an average annual incidence of 8.7 inpatients per 10,000 residents, among the highest frequencies worldwide.

ConclusionsThe hospital database reflects the geographic distribution of severe, but not mild, mental illness within Caldas. Each hotspot is a candidate location for further research to identify genetic or environmental risk factors for severe mental illness. Our analyses highlight how existing infrastructure from middle-income countries can be extraordinary resources for population studies.

category: psychiatry and clinical psychology


title: Relative Effectiveness of Four Doses Compared to Three Dose of the BNT162b2 Vaccine in Israel

abstract:
ObjectivesThe rapid spread of the Omicron variant (B.1.1.529) alongside evidence of a relatively rapid waning of the third dose prompted Israel to administer a fourth dose of the BNT162b2 vaccine on January 2022. Thus far, sufficient real-world evidence demonstrating the effectiveness of a fourth dose against infection and severe COVID-19 are lacking. This study examined the short-term effectiveness of a fourth dose compared to three doses over the span of 10 weeks.

DesignA retrospective test-negative case-control study, performing both a matched analysis and an unmatched multiple-tests analysis.

SettingNationally centralized database of Maccabi Healthcare Services (MHS), an Israeli national health fund that covers 2.5 million people.

ParticipantsThe study population included 97,499 MHS members aged 60 or older who were eligible to receive a fourth vaccine dose and performed at least one PCR test during the study period. Of them, 27,876 received the fourth dose and 69,623 received only three doses.

Main outcomes and measuresAnalyses focused on the period from January 10, 2022 (7 days after the fourth dose was first administered to eligible individuals) to March 13, 2022, an Omicron-dominant period in Israel. We evaluated two SARS-CoV-2-related outcomes: (1) breakthrough infection, defined as a positive PCR test performed 7 or more days after inoculation with the BNT162b2 vaccine; and (2) breakthrough infection resulting in a severe disease, defined as COVID-19-related hospitalization or COVID-19 associated mortality.

ResultsA fourth dose provided considerable additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, vaccine effectiveness against infection varied over time, peaking during the third week with a VE of 64% (95% CI: 62.0%-65.9%) and declining to 29.2% (95% CI: 17.7%-39.1%) by the end of the 10-week follow-up period. Unlike VE against infection, the relative effectiveness of a fourth dose against severe COVID-19 was maintained at high level (>73%) throughout the 9-week follow-up period. Importantly, severe disease was a relatively rare event, occurring in <1% of both fourth dose and third dose only recipients.

ConclusionsA fourth dose of the BNT162b2 vaccine provided considerable additional protection against both SARS-CoV-2 infection and severe disease relative to three doses of the vaccine. However, effectiveness of the fourth dose against infection wanes sooner than that of the third dose.


title: The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) patient-reported outcome measure for Long Covid or Post-COVID syndrome

abstract:
BackgroundThe C19-YRS was the first validated scale reported in the literature for patient assessment and monitoring in Long Covid or Post-COVID syndrome. The 22-item scale contains four subscales measuring symptom severity, functional disability, overall health and additional symptoms.

ObjectivesThis study aimed to modify and refine the scale based on psychometric properties, emerging evidence on additional Long Covid symptoms, and feedback from a working group of patients and healthcare professionals.

MethodsData were collected from 370 patients who completed the C19-YRS scale in a community Long COVID service. The psychometric properties of the Symptom Severity and Functional Disability subscales were assessed using a Rasch Measurement Theory framework, where all individual scale items were assessed for model fit, local dependency, response category functioning and differential item functioning (DIF) by age group and sex. Additionally, the subscales were assessed for targeting, reliability and unidimensionality. The overall health subscale is a single item, and the additional symptoms subscale is not intended to be summed, therefore neither is appropriate for Rasch analyses. Psychometric results and implications were relayed back to the working group for discussion, alongside clinical evidence of emerging and relevant symptoms not covered by the original C19-YRS.

ResultsRasch analysis revealed promising psychometric properties of the symptom severity and functional disability subscales, with both displaying good targeting and reliability, although some individual measurement anomalies were noted. The original 0-10 item response category structure did not operate as intended for both the subscales. Post-hoc rescoring suggested that a 4-point response category structure would be more appropriate for both the subscales, and this aligned with patient feedback. This scoring change was implemented, alongside changes in the item composition of the symptom severity and additional symptoms subscales. The functional disability item set, and the overall health single-item subscale remained unchanged.

ConclusionA modified version of the C19-YRS was developed based on a combination of psychometric evidence, clinical relevance of the content and feedback from the working group (comprising patients and healthcare professionals). Future studies including NIHR funded LOCOMOTION study will undertake large-scale, multi-centre validation of the modified C19-YRS.

category: rehabilitation medicine and physical therapy


title: Production of anti-spike antibodies in response to COVID vaccine in lymphoma patients

abstract: Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. There is limited data on the efficacy of the COVID vaccines in lymphoma patients, and to suggest the optimal timing of vaccination to elicit immunity in patients receiving immunochemotherapy. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody titer following the primary COVID vaccination series. The primary series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fishers exact test, and unadjusted and adjusted logistic regression models were used for univariate (UVA) and multivariate (MVA) analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitts, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); and 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p=0.04). Lymphoma patients are capable of mounting a humoral response to the COVID mRNA vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

category: oncology


title: International Travel-Related Control Measures to contain The Covid-19 Pandemic: An update to a Cochrane Rapid Review

abstract:
BackgroundCOVID-19 has proven to be more difficult to manage for many reasons including its high infectivity rate. One of the potential ways to limit its spread is by controlling international travel. The objective of this systematic review is to identify, critically-appraise and summarize evidence on international travel-related control measures.

MethodsThis review is based on the Cochrane review: International travel-related control measures to contain the COVID-19 pandemic and followed the same methods. In brief, we searched for clinical and modelling studies in general health and COVID-19-specific bibliographic databases. The primary outcome categories were (i) cases avoided, (ii) a shift in epidemic development and, (iii) cases detected. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome.

ResultsWe assessed 66 full-text articles that met with our inclusion criteria. Seventeen new studies (modelling = 9, observational = 8) were identified in the updated search. Most studies were of critical to moderate risk of bias. The added studies did not change the main conclusions of the Cochrane review nor the quality of the evidence (very low to low certainty). However, it did add to the evidence base for most outcomes.

ConclusionsWeak evidence supports the use of international travel-related control measures to limit the spread of COVID-19 via air travel. Real-world studies are required to support these conclusions.


title: Intubation and Inhospital mortality in trauma patients with Glasgow Coma Scale Score eight or less. A multicenter cohort study.

abstract:
BackgroundMost trauma societies recommend intubation of trauma patients with Glasgow coma scale (GCS) [≤] 8, without robust evidence supporting it.

MethodsWe examined the association between intubation and inhopital 30 day mortality in trauma patients arriving with GCS [≤] 8. The data were obtained using the Towards Improved Trauma Care Outcomes (TITCO) registry in India cohort. We compared the outcomes of patients with GCS [≤] 8 who were intubated within one hour after arrival with those who were intubated later or not at all, using multiple analytical approaches to evaluate the consistency of the findings. We also examined the association in multiple subgroups to identify any variability of the effect.

ResultsOf 3476 patients who arrived with a GCS [≤] 8, 1671 (48.1%) were intubated within an hour and 1805 (51.9%) were intubated later or not intubated at all. Overall, 1957 (56.3%) patients died in whole cohort. A total of 947 (56.7%) patients died in intubation group and 1010 (56%) died in non intubation group. In the main analysis, there was no significant association between intubation within an hour and mortality(OR=1.18,[CI,0.76-1.84], p value = 0.467). This result was consistent across multiple sensitivity analysis.

ConclusionIn this observational study of trauma patients with GCS [≤] 8, who present to tertiary care hospitals, intubation within one hour after arrival was not associated with increased or decreased risk of inhospital mortality compared to intubation after one hour or no intubation. Further studies are needed to precisely evaluate the benefit of intubation and thus supporting the recommendations.

category: emergency medicine


title: Vaccine Adverse Event Reporting System (VAERS): Evaluation of 31 Years of Reports and Pandemics' Impact

abstract:
BackgroundVaccine adverse event reporting system (VAERS) was established in the United States (U.S.) as an early warning system with a main purpose of collecting postmarketing adverse events following immunizations (AEFIs) reports to monitor the vaccine safety and to mitigate the risks from vaccines. During the coronavirus diseases 2019 (COVID-19) pandemic, VAERS got more attention as its important role in monitoring the safety of the vaccines. Thus, the aim of this study was to investigate VAERS patterns, reported AEFIs, adverse events of special interest (AESIs), impact of different pandemics since its inception, and surveillance rate of serious vs nonserious AEFIs.

MethodsThis was an observational study using VARES data from 2/7/1990 to 12/11/2021. Patterns of reports over years were first described, followed by a comparison of reports statistics per year. Furthermore, a comparison of incidents (death, ER visits, etc.) statistics over years, in addition to statistics of each vaccine were calculated. Moreover, each incidents statistics for each vaccine were calculated and top vaccines were reported. Finally, survival analysis utilizing cox regression was done, in addition to AESIs distribution stratified by age groups and gender. All analyses were conducted using R (Version 1.4.1717) and Excel for Microsoft 365.

ResultsThere were 1,396,280 domestic and 346,210 non-domestic reports during 1990-2021, including 228 vaccines. For both domestic and non-domestic reports, year of 2021 had the highest reporting rate (48.52% and 70.33%), in addition a notable changes in AEFIs patterns were recorded during 1991, 1998, 2000, 2006, 2009, 2011, and 2017. AEFIs were as follow: deaths (1.00% and 4.08%), ER or doctor visits (13.37% and 2.27%), hospitalizations (5.84% and 27.78%), lethal threat (1.42% and 4.38%), and disabilities (1.4% and 7.96%). Pyrexia was the top reported symptom during the past 31 years, except for 2021 where headache was the top one. COVID-19 vaccines namely Moderna, Pfizer-Biontech, and Janssen were the top 3 reported vaccines with headache, pyrexia, and fatigue as the top associated AEFIs. Followed by Zoster, Seasonal Influenza, Pneumococcal, and Human papillomavirus vaccines. Myocarditis or Pericarditis were the top reported AESIs (26.95% and 25.84%). Male (HR:1.15, 1.14 - 1.16) for domestic (HR:1.23, 1.22 -1.25) for nondomestic have a higher probability of having serious AEFIs. In addition, age group [≤] 5 years old in domestic and >84 years old in nondomestic have a higher probability of having AEFIs compared to other age groups.

ConclusionsThe large data available in VARES make it a useful tool for detecting and monitoring vaccine AEFIs. However, its usability relies on understating the limitations of this surveillance system, the impact of governmental regulations, availability of vaccines, and public health recommendations on the reporting rate.


title: Assessing Direct and Spillover Effects of Intervention Packages in Network-Randomized Studies

abstract: Intervention packages may result in a greater public health impact than single interventions. Understanding the separate impact of each component in the overall package effectiveness can improve intervention delivery. We propose an approach to evaluate the effects of a time-varying intervention package in a single study. In some network-randomized studies, only a subset of participants in exposed networks receive the intervention themselves. The spillover effect contrasts potential outcomes of persons not exposed themselves under intervention in the network versus no intervention in a control network. We estimated effects of components of the intervention package in HIV Prevention Trials Network 037, a Phase III network-randomized HIV prevention trial among people who inject drugs and their risk networks using Marginal Structural Models to adjust for time-varying confounding. The index participant in an intervention network received a peer education intervention initially at baseline, then boosters at 6 and 12 months. All participants were followed to ascertain HIV risk behaviors. There were 560 participants with at least one follow-up visit, 48% of whom randomized to the intervention, and 1,598 participant-visits were observed. The spillover effect of the boosters in the presence of initial peer education training was a 39% rate reduction (95% confidence interval (CI) = -57%, -13%). These methods will be useful for evaluation of intervention packages in studies with network features.


title: Informal Sector Employment and the Health Outcomes of Older Workers in India

abstract: A large proportion of the older population in India constitutes an undeniable share of workforce after the retirement age. This stresses the need to understand the implications of working at older ages on health outcomes. The main objective of this study is to examine the variations in health outcomes by formal/informal sector of employment of older workers using the Longitudinal Ageing Study in India. Using binary logistic regression models with interaction terms, the results of this study affirm that type of work does play a significant role in determining health outcomes even after controlling socio-economic, demographic, life-style behaviour, and work characteristics. The risk of Poor Cognitive Functioning (PCF) is high among informal workers, while formal workers suffer greatly from Chronic Health Conditions (CHC) and Functional Limitations (FL). The presence of CHC among informal workers is more damaging because it elevates their FL, whereas for formal workers presence of FL is unfavourable because it deteriorates their cognitive functioning. Therefore, present study underscores the relevance of policies focusing on providing health and healthcare benefits by respective economic activity and socio-economic position of older workers.


title: Stairway visual contrast enhancement to reduce fall-related events

abstract:
Falls on stairs occur frequently and pose a significant health and financial risk. Laboratory research has found that fall frequency can be reduced through contrast enhancement of the stairs by applying vinyl striping to the first and last steps faces, and all the steps top edges. Here we sought to determine if such step contrast enhancement can reduce the probability of fall-related events such as loss of balance, slips, trips, and falls in public university staircases. Cameras were used to capture stair users ascent and descent on contrast enhanced ( striped) and control stairways. Observed age group, observed gender, traverse direction (ascent, descent), fall-related events, and walking speed (m/s) were recorded. Fall-related events were reduced for the striped stairway compared to the control stairway (odds ratio = 2.87, average marginal effect = 0.002, p = .023) when controlling for observed gender, age category, and traverse direction. These results suggest contrast enhancement of first and last steps face and all steps edges may reduce fall- related events in public settings. Adding contrast enhancement to public stairways is a simple and cost-effective way to reduce the loss of balance, slips, and trips that could lead to catastrophic falls on stairs as well as the health and financial burden associated with such falls.

PRECISContrast enhancement of stairway features may be a simple and cost-effective way to reduce falls on stairs. We show that monochrome striping on the first and last steps faces and black stripes on steps top edges reduce the probability of fall-related events in public stairways.


title: COVID-19 outcomes associated with clinical and demographic characteristics in patients hospitalized with severe and critical disease in Peshawar

abstract:
BackgroundAs a novel disease, understanding the relationship between the clinical and demographic characteristics of coronavirus disease 2019 (COVID-19) patients and their outcome is critical. We investigated this relationship in hospitalized patients in a tertiary healthcare setting.

Aims/objectivesTo study COVID-19 severity and outcomes in relation to clinical and demographic characteristics of in admitted patients

MethodologyIn this cross-sectional study, medical records for 1087 COVID-19 patients were reviewed to extract symptoms, comorbidities, demographic characteristics, and outcomes data. Statistical analyses included the post-stratification chi-square test, independent sample t-test, multivariate logistic regression, and time-to-event analysis.

ResultsThe majority of the study participants were >50 years old (67%) and male (59%) and had the following symptoms: fever (96%), cough (95%), shortness of breath (73%), loss of taste (77%), and loss of smell (77%). Regarding worst outcome, multivariate regression analysis showed that these characteristics were statistically significant: shortness of breath (adjusted odds ratio [aOR] 31.3; 95% CI, 11.87-82.53; p < 0.001), intensive care unit (ICU) admission (aOR 28.3; 95% CI,9.0-89.6; p < 0.001), diabetes mellitus (aOR 5.1; 95% CI;3.2-8.2; p < 0.001), ischemic heart disease (aOR 3.4; 95% CI,1.6-7; p = 0.001), nausea and vomiting (aOR 3.3; 95% CI, 1.7-6.6; p = 0.001), and prolonged hospital stay (aOR 1.04; 95% CI, 1.02-1.08; p = 0.001), while patients with rhinorrhea were significantly protected (aOR 0.3; 95% CI, 0.2-0.5; p < 0.001). A Kaplan-Meier curve showed that the symptoms of shortness of breath, ICU admission, fever, nausea and vomiting, and diarrhea increased the risk of mortality.

ConclusionIncreasing age, certain comorbidities and symptoms, and direct admission to the ICU increased the risk of worse outcomes. Further research is needed to determine risk factors that may increase disease severity and devise a proper risk-scoring system to initiate timely management.

category: respiratory medicine


title: Birth history is associated with whole-blood and T-cell methylation patterns in relapse onset multiple sclerosis

abstract:
BackgroundPregnancy in women with multiple sclerosis (MS) is associated with a reduction of long-term disability progression. The mechanism that drives this effect is unknown, but converging evidence suggests a role for epigenetic mechanisms altering immune and/or central nervous system function.

ObjectivesWe aimed to identify whole blood and immune cell-specific DNA methylation patterns associated with parity in relapse-onset multiple sclerosis.

MethodsWe compared whole-blood methylation patterns between 96 matched pairs of nulligravida and parous females with MS (n=192). Parity was defined as at least one term or pre-term birth, and nulligravida was defined as no prior pregnancies. Methylation was measured with Illumina EPIC arrays, and data was pre-processed and statistically analysed using the ChAMP package. Cell-type proportions were estimated using the EpiDISH package, and cell-specific analysis conducted using linear regression. Gene-set enrichment analysis (GSEA) was performed with ToppGene API and GOmeth. Methylation age was calculated with the methyAge package. Methylation age acceleration (MAA) was calculated by regressing methylation age on chronological age. FDR<0.05 was used to assess significance.

ResultsThe median time from last pregnancy to blood collection was 16.66 years (range = 1.45 - 44.42 years). We identified 903 differentially methylated positions (DMPs) in whole blood; 365 were hypomethylated and 528 were hypermethylated in parous women. We further identified two differentially methylated regions (DMRs) in CRYGN on Chromosome 7 and an intergenic region on Chromosome 15. There were four and eight cell type specific DMPs in CD4+ and CD8+ cells, respectively. Differentially methylated genes were enriched in neuronal plasticity pathways. Parity was associated with reduced MAA by a mean of 1.44 to 2.27 years using the PhenoAge (p = 0.002) and GrimAge (p = 0.005) algorithms.

ConclusionWhole-blood methylation patterns are associated with birth history in females with relapse-onset multiple sclerosis. We found enrichment of differentially methylated genes encoding neuronal processes and reduced MAA in parous women. These methylation changes could mediate the long-term benefit of pregnancy for disease progression in multiple sclerosis.


title: Environmental risks and occupational health hazards of bidi workers and their communities in India: protocol for systematic scoping review

abstract:
BackgroundTobacco consumption is a leading preventable cause of disease and premature deaths. In India bidis are the most common form of smoking tobacco product. Bidi manufacturing is an agro-forest based cottage industry and is generally rolled at home. These workers are exposed to nicotine, tar and other particles through skin leading to occupational health risks in not only themselves but also in their families and communities. There are concerns on environmental risks of bidi manufacturing in home too.

AimTo assess the environmental risks and occupational health hazards of bidi workers and their communities in India.

MethodWe will conduct a scoping review to identify, map and analyse evidence around environmental risks and occupational health hazards in bidi workers and their families and communities. We will search in seven electronic databases (PubMed, EMBASE+EMBASE Classic, CINAHL, Environment complete-EBSCO, GreenFILE-EBSCO, Web of Science and WHO-IRIS). Screening will be done independently by at least two reviewers, with disagreements resolve by consensus. We will extract data for the included studies using a standardised data extraction in an independent fashion, with disagreements resolved by consensus. We will conduct a narrative synthesis.

category: occupational and environmental health


title: Effects of genetic liability to Alzheimers disease on circulating metabolites across the life course

abstract:
ObjectiveAlzheimers disease (AD) has several known genetic determinants, yet the mechanisms through which they lead to disease onset remain poorly understood. This study aims to estimate the effects of genetic liability to AD on plasma metabolites measured at seven different stages across the life course.

MethodsGenetic and metabolomic data from 5,648 offspring from the Avon Longitudinal Study of Parents and Children birth cohort were used. Linear regression models examined the association between higher AD liability, as measured by a genetic risk score (GRS), and plasma metabolites measured at 8, 16, 18 and 25 years of age. Two hundred twenty-nine metabolites were studied, most relating to lipid/lipoprotein traits. Two-sample Mendelian randomization was performed using summary statistics from age-stratified genome-wide association studies (GWAS) of the same metabolites for 118,466 participants from the UK Biobank, to examine the persistence of any AD liability effects into late adulthood.

ResultsThe GRS including the APOE4 isoform demonstrated the strongest positive associations for cholesterol-related traits per doubling of genetic liability to AD, e.g., for low-density lipoprotein cholesterol (LDL-C) at age 25yrs (0.12 SD; 95% CI 0.09, 0.14), with similar magnitudes of association across age groups in ALSPAC. In the UK Biobank, the effect of AD liability decreased with age tertile for several lipid traits (e.g., LDL-C, youngest: 0.15 SD; 95% CI 0.07, 0.23, intermediate: 0.13 SD; 95% CI 0.07, 0.20, oldest: 0.10 SD; 95% CI 0.05, 0.16). Across both cohorts, the effect of AD liability on high-density lipoprotein cholesterol (HDL-C) attenuated as age increased. Fatty acid metabolites also demonstrated positive associations in both cohorts, though smaller in magnitude compared with lipid traits. Sensitivity analyses indicated that these effects were driven by the APOE4 isoform.

ConclusionsThese results support a profound influence of the APOE4 isoform on circulating lipids and fatty acids from early life to later adulthood. Such lipid and fatty acid traits may be implicated in early AD pathogenesis and warrant further investigation as potential targets for preventing the onset of AD.

category: genetic and genomic medicine


title: A mixed methods study of community-based health insurance enrollment trends and underlying challenges in two districts of northeast Ethiopia: a proxy for its sustainability

abstract:
BackgroundCommunity-based health insurance initiatives in low- and middle-income countries are plagued by persistently low coverage due to their voluntary orientation. In Ethiopia, the schemes membership growth has not been well investigated so far. This study sought to examine the schemes enrollment trend over a five-year period, and to explore the various challenges that underpin membership growth from the perspectives of various key stakeholders.

MethodsThe study employed a mixed methods case study in two districts of northeast Ethiopia: Tehulederie and Kallu. Quantitative data was collected by reviewing the databases of schemes. Key informant interviews and in-depth interviews were conducted face-to-face with 19 key stakeholders and nine community members, respectively. Study participants were purposely selected using the maximum variation technique. Interviews were audio recorded, transcribed verbatim, and translated into English. Thematic analysis was employed with both deductive and inductive coding approaches.

ResultsEnrollment in the two districts has shown an inconsistent trend over the study period (2017 to 2021). The scheme in Tehulederie has a relatively better enrollment trend, particularly in terms of membership retention, which could be due to the strong foundation laid by a rigorous public awareness campaign and technical support during the pilot phase. The challenges contributing to the observed level of performance have been summarized under four main themes that include quality of health care, claims reimbursement for insurance holders, governance practices, and community awareness and acceptability.

ConclusionsThe scheme experienced negative growth ratios in both districts with inconsistent trends, showing that the scheme is not functionally viable. It will regress unless relevant stakeholders at all levels of government demonstrate political will and commitment to its implementation, as well as advocate for the community. Interventions should target on the highlighted challenges in order to boost membership growth and ensure the viability of the community-based health insurance.

category: health economics


title: Strengthening health service delivery and governance through institutionalizing "Urban Health Atlas" - a geo-referenced Information Communication and Technology tool: lessons learned from an implementation research in three cities in Bangladesh

abstract:
IntroductionUrban health governance in Bangladesh is complex as multiple actors are involved and no comprehensive data are currently available on infrastructure, services, or performance either in public and private sectors of the healthcare system. The Urban Health Atlas (UHA) - a novel and interactive geo-referenced, web-based visualization tool was developed in Bangladesh to provide geospatial and service information to decision makers involved in urban health service planning and governance. Our objective was to study the opportunities for institutionalization of the UHA into government health systems responsible for urban healthcare delivery and document the facilitators and barriers to its uptake.

MethodsThis mixed-methods implementation research was carried out during 2017-2019 in three cities in Bangladesh: Dhaka, Dinajpur and Jashore. During the intervention period, six hands-on trainings on UHA were provided to 67 urban health managers across three study sites. Both in-depth and key informant interviews were conducted to understand user experience and document stakeholder perceptions of institutionalizing UHA.

ResultsCapacity building on UHA enhanced understanding of health managers around its utility for service delivery planning, decision making and oversight. Uptake of UHA was challenged by inadequate ICT infrastructure, shortage of human resources and general lack of ICT skill among the managers. Motivating key decision makers and stakeholders about the potential of UHA and engaging them from the inception helped the institutionalization process.

ConclusionWhile uptake of UHA by government health managers appears possible with dedicated capacity building initiatives, its use and regular update are challenged by multiple factors at the implementation level. A clear understanding of context, actors and system readiness is foundational in determining whether the institutionalization of health ICTs is timely, realistic or relevant.

category: health systems and quality improvement


title: Booster dose of BNT162b2 in a CoronaVac primary vaccination protocol improves neutralization of SARS-CoV-2 Omicron variant

abstract: The emergence of the new SARS-CoV-2 Omicron variant, which is known to accumulate a huge number of mutations when compared to other variants, brought to light the concern about vaccine escape, especially from the neutralization by antibodies induced by vaccination. In this scenario, we evaluated the impact on antibody neutralization induction, against Omicron variant, by a booster dose of BNT162b2 mRNA vaccine after the CoronaVac primary vaccination scheme. The percentage of seroconverted individuals 30 and 60 days after CoronaVac scheme was 17% and 10%, respectively. After booster dose administration, the seroconvertion rate increased to 76.6%. The neutralization mean titer against Omicron in the CoronaVac protocol decreased over time, but after the booster dose, the mean titer increased 43.1 times, indicating a positive impact of this vaccine combination in the serological immune response.


title: Vaccine Effectiveness Against Hospitalization Among Adolescent and Pediatric SARS-CoV-2 Cases in Ontario, Canada

abstract:
BackgroundVaccines to prevent SARS-CoV-2 infection and severe outcomes were approved in 2021 for adolescent and subsequently pediatric populations. With the emergence of variants of concern, it is important to continue to assess vaccine effectiveness against both infection and severe disease manifestations.

MethodsUsing an age and time-matched nested case-control design, we estimated the vaccine effectiveness of SARS-CoV-2 vaccination at preventing hospitalization among adolescent and pediatric patients infected with SARS-CoV-2. We linked SARS-CoV-2 cases ages 4 to 17 years in Ontarios reportable diseases database to SARS-CoV-2 vaccination records. We included 1,441 incident SARS-CoV-2 cases occurring between May 28, 2021 and January 10, 2022. We used multivariable logistic regression to estimate the effectiveness of one and two mRNA vaccine doses against hospitalization among adolescent and pediatric SARS-CoV-2 cases. We quantified and mitigated the impact of unmeasured confounding by calculating an E-value and by applying instrumental variable methods.

ResultsWe included n=131 hospitalized SARS-CoV-2 cases and n=1,310 non-hospitalized SARS-CoV-2 cases. One vaccine dose was shown to be 37% effective against hospitalization among SARS-CoV-2 cases (adjusted odds ratio [aOR] = 0.63 [95% CI: 0.33, 1.13]). In contrast, two doses were 59% (aOR = 0.41 [95% CI: 0.21, 0.77]) effective at preventing hospitalization among SARS-CoV-2 cases.

ConclusionsEven with immune evasion by SARS-CoV-2 variants, two vaccine doses continue to provide protection against hospitalization among adolescent and pediatric patients, even when the vaccines do not prevent infection. SARS-CoV-2 vaccines remain a safe and effective intervention to prevent severe outcomes.


title: Impact of Vaccination, Prior Infection, and Therapy on Delta and Omicron Variants

abstract: We studied 249,070 patients who were tested for SARS-CoV-2 in the Cleveland Clinic Health System between October 1, 2021 and January 31, 2022. We found that vaccination, especially with recent boosting, was more effective than prior infection and monoclonal antibody therapy against both the delta and omicron variants. Vaccination and prior infection were much less effective against infection with the omicron variant than with the delta variant, but the opposite was true of death after infection. Boosting greatly increased the effectiveness of the two mRNA vaccines against both infection and death, although its effects waned markedly after 6 months. In addition, monoclonal antibody therapy was notably less effective at preventing death from the omicron variant than from the delta variant. Finally, the relatively low mortality of the omicron variant was due to both the reduced lethality of this variant and the increased population immunity acquired from booster vaccination and previous infection.


title: Species-specific bacterial detector for fast pathogen diagnosis of severe pneumonia patients in the intensive care unit

abstract: Rapid diagnosis of pathogens is the cornerstone of appropriate therapy and is also a great challenge to be overcome. Although NGS and some other PCR-based pathogen detection methods were applied to improve the speed and accuracy of clinical diagnosis, it was still a long way from the clinical needs of rapid and accurate diagnostic therapy in the intensive care unit (ICU). In this study, we aimed at developing a new rapid diagnostic tool, Species-Specific Bacterial Detector (SSBD), to evaluate the existence and quantification of 10 most usual pathogenic bacteria in ICU in 4 hours. Briefly, the species-specific genome fragments of each bacterium were identified by our algorithm using 1791 microbe genomes from 232 species and then used to combine with CRISPR/Cas12 to establish diagnosis tools. Based on the tests of 77 samples, SSBD demonstrated 100% sensitivity and 87% specificity compared with conventional culture test (CCT). Later on, an interventional random-grouped study was applied to evaluate the clinical benefits of SSBD. Briefly, SSBD demonstrated more accurate and faster diagnosis results and led to earlier antibiotics adjustment than CCT. Based on the results acquired by SSBD, cultivation results could deviate from the real pathogenic situation with polymicrobial infections. In addition, nosocomial infections were found widely in ICU, which should deserve more attention.

category: intensive care and critical care medicine


title: Association of genetically-predicted lipid traits and lipid-modifying targets with the risk of heart failure

abstract:
AimsTo assess the association of lipid traits and lipid-modification via licensed or investigational targets with heart failure (HF) risk using 2-sample Mendelian randomization (MR) study.

Methods and resultsGenetic variants obtained from genome-wide association studies (GWASs) in UK Biobank as instrumental variables to investigate the association of lipid traits (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (ApoB) and apolipoprotein AI (ApoAI)) and lipid-modifying effect of eight licensed or investigational drug targets with HF risk by using the inverse-variance weighted method. In this study, we observed that genetically-predicted levels of LDL-C, TG, LDL-C and ApoB were significantly related to HF risk, which were mainly mediated by CHD. Further MR analyses identified PCSK9, CETP and LPL, but not HMGCR, as potential targets to prevent HF. The genetic proxy of LDL-C and ApoB increase modified by PCSK9 showed similar evidence in increasing risk of HF (PLDL-C=1.27*10-4; PApoB=1.94*10-4); CETP played a role in HF risk via modifying all investigational lipid traits with the strongest evidence though ApoB (P=5.87*10-6); LPL exerted effects on HF via modifying most lipid traits with the strongest evidence observed via modifying TG (P=3.73*10-12).

ConclusionsThis 2-sample MR study provided genetic evidence of the associations between lipid traits and HF risk, which were mostly mediated by CHD. Besides, drug target MR studies indicated that PCSK9 inhibition, CETP inhibition and LPL activation, but not statins, were effective in reducing HF risk.


title: Understanding the role of mask-wearing during COVID-19 on the island of Ireland

abstract:
BackgroundNon-pharmaceutical interventions (NPI) play a key role in managing epidemics, yet it is challenging to evaluate their impacts on disease spread and outcomes.

MethodsTo estimate the effect of a mask-wearing intervention to mitigate the spread of SARS-CoV-2 on the island of Ireland, we focused on the potential for interindividual infectious contact over time as the outcome. This is difficult to measure directly; in a companion paper we estimated it using a multi-strain epidemiological model. We used data on mask-wearing and mobility in both Northern Ireland (NI) and the Republic of Ireland (ROI) to predict independently the estimated infectious contact over time. We made counterfactual predictions of infectious contact rates and hospitalisations under a hypothetical intervention where 90% of the population were wearing masks during early 2020, when in reality few people were wearing masks in public; this was mandated in both jurisdictions on 10th August 2020.

ResultsThere were 1601 hospitalisations with COVID-19 in NI between 12th March and 10th August 2020, and 1521 in ROI between 3rd April and 10th August 2020. Under the counterfactual mask-wearing scenario, we estimated 512 (95% CI 400, 730) hospitalisations in NI, and 344 (95% CI 266, 526) in ROI, during the same periods.

ConclusionsWe have estimated a large effect of population mask-wearing on COVID-19 hospitalisations. This could be partly due to other factors that were also changing over time.


title: Modestly protective cytomegalovirus vaccination of young children effectively prevents congenital infection at the population level

abstract: A vaccine to prevent congenital cytomegalovirus infection (cCMV) is a public health priority. cCMV results from maternal primary or non-primary CMV infection (reinfection or reactivation of chronic infection) during pregnancy. Young children are a major source of transmission to pregnant women because they shed CMV at high viral loads for prolonged periods. CMV vaccines evaluated in clinical trials so far have demonstrated only approximately 50% efficacy against maternal primary infection. None of these have been approved, as higher levels of vaccine-induced immunity are assumed to be required to substantially reduce cCMV prevalence. Here, we designed a mathematical model to capture the relationship between viral shedding by young children and maternal CMV infections during pregnancy. Using this model, we were able to quantify the efficacy of CMV immunity following infection to protect against reinfection and viral shedding. There was a 35% reduction in the risk of infection to a seropositive person (reinfection) versus a seronegative person (primary infection), given the same exposure. Viral shedding following reinfection was only 25% the quantity of that following primary infection. We also found that a vaccine that confers the equivalent of infection-induced immunity, when given to young children, markedly reduces both CMV transmission to pregnant women and rates of cCMV. Thus, we predict that vaccine candidates that have already been shown to be only modestly protective may in fact be highly effective at preventing cCMV by interrupting child-to-mother transmission.


title: Vaccine effectiveness with BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine against reported SARS-CoV-2 Delta and Omicron infection among adolescents, Norway, August 2021 to January 2022

abstract:
BackgroundCOVID-19 vaccination was recommended for adolescents in Norway since August 2021. In this population-based cohort study, we estimated the BNT162b2 vaccine effectiveness against any PCR-confirmed (symptomatic or not) SARS-CoV-2 infections caused by the Delta and Omicron variant among adolescents (12-17-years-old) in Norway from August 2021 to January 2022.

MethodsUsing Cox proportional hazard models, we estimated the BNT162b2 vaccine effectiveness against any Delta and Omicron infections. Vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data were obtained from the National Preparedness registry for COVID-19, which contains individual-level data from national health and administrative registries.

FindingsVaccine effectiveness against Delta infection peaked at 68% (95%CI: 64-71%) and 62% (95%CI: 57- 66%) in days 21-48 after the first dose among 12-15-year-olds and 16-17-year-olds respectively. Among 16-17-year-olds that received two doses, vaccine effectiveness peaked at 93% (95%CI: 90-95%) in days 35-62 and declined to 84% (95%CI: 76-89%) in 63 days or more after the second dose. For both age-groups, we found no protection against Omicron infection after receiving one dose. Among 16-17-year-olds, vaccine effectiveness against Omicron infection peaked at 53% (95%CI: 43-62%) in 7-34 days after the second dose and decreased to 23% (95%CI: 3-40%) in 63 days or more after vaccination. Vaccine effectiveness decreased with time since vaccination for both variants, but waning was observed to occur faster for Omicron.

InterpretationOur results suggest reduced protection from BNT162b2 vaccination against any SARS-CoV-2 infection caused by the Omicron variant compared to the Delta. In addition, waning immunity was observed to occur faster for Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance.

FundingNo funding was received.

Research in context

Evidence before this studyBNT162b2 (Comirnaty, Pfizer-BioNTech) and mRNA-1273 (Spikevax, Moderna) vaccines have been approved for use in adolescents, based on results from randomized placebo-controlled trials demonstrating comparable immunogenicity and safety profile as in young adults. In addition, observational studies from Israel, the USA and England have reported high protection of BNT162b2 vaccines against SARS-CoV-2 Delta infection among adolescents. These studies also reported decrease in effectiveness with time since last vaccine dose. Evidence on the effect of an extended interval between doses, longer time since vaccination and the effect against different variants is limited. When we first planned this study in early February 2022, no data were available regarding vaccine effectiveness against SARS-CoV-2 Omicron infection among adolescents. To our knowledge when we completed this study and before submitting this article, only one study from England reported results in a preprint on vaccine effectiveness against symptomatic SARS-CoV-2 Omicron infection among adolescents. We searched for studies that evaluated vaccine efficacy or effectiveness after vaccination of adolescents during 2021-2022 in PubMed, medRxiv, bioRxiv, SSRN. We searched for studies with several variations of the primary key search terms "COVID-19", "SARS-CoV-2", and "vaccine" (including names of specific vaccines, as BNT162b2), "vaccine effectiveness", "adolescents", "children".

Added value of this studyThe rapid increase in the incidence of SARS-CoV-2 infection caused by the Omicron variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines in adults but also adolescents. In this population-based cohort study, we showed that the vaccine effectiveness against Omicron is lower than against Delta infections among adolescents, including symptomatic and asymptomatic infections. We should note that evidence suggests higher rates of asymptomatic carriage for Omicron than other variants of concern. Vaccine effectiveness that includes asymptomatic cases, as in the study from England, is expected to be lower than when including symptomatic cases only. We found that one and two doses of BNT162b2 among adolescents protected well against Delta. Vaccination provided high protection against Delta infections (>91%) among Norwegian 16-17-year-olds 7-62 days after the second dose. We found no protection against Omicron SARS-CoV-2 infection after one vaccine dose, and moderate effectiveness after two doses (peaked at 53%) among the 16-17-year-olds. Moreover, waning immunity was observed to occur faster for Omicron.

Implications of all the available evidenceBased on the available evidence, the vaccine effectiveness among adolescents is similar to that reported among adults, also with an extended period of 8-12 weeks between doses which was used in Norway. Protection is significantly lower against Omicron than Delta infections and immunity wanes faster against Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance. Policies should take into account the impact of vaccination campaigns among adolescents and their primary objective. Vaccine effectiveness should be re-evaluated when other variants appear as they might have different outcomes as shown between Delta and Omicron infections.


title: THE IMPACT OF ROUTINES ON EMOTIONAL AND BEHAVIOURAL DIFFICULTIES IN CHILDREN AND ON PARENTAL ANXIETY DURING COVID-19

abstract:
Aims and hypothesisWe hypothesised that there would be an association between maintaining a routine during lockdown and both lower emotional and behavioural difficulties in children and lower parental anxiety. We also hypothesised that children of  keyworker parents would have fewer emotional and behavioural symptoms due to having maintained more normal routines.

BackgroundThe Covid-19 pandemic and related public health measures have impacted on mental health of children.

MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to explore associations between maintaining a routine, and emotional and behavioural difficulties in children, using linear regression models. We included measures of parental anxiety. We separately explored associations with having a keyworker parent. We used the Carey Infant Temperament Questionnaire and the Revised Rutter Parent Scale for Preschool Children to establish levels of emotional and behavioural difficulties.

Results289 parents completed questionnaires about their 411 children. Keeping a routine was associated with emotional and behavioural difficulty scores 5.0 points lower (95% CI -10.0 to - 0.1), p=0.045 than not keeping a routine. Parents who reported keeping a routine had anxiety scores 4.3 points lower (95% CI -7.5 to -1.1), p=0.009 than those who did not. Children of keyworkers tended to have lower emotional and behavioural difficulty scores (-3.1 (95%CI -6.26 to 0.08), p=0.056) than children of non-keyworkers. All models were adjusted for relevant potential confounders.

ConclusionMaintaining a routine may be beneficial for both child emotional wellbeing and parental anxiety, although it is also possible that lower parental anxiety levels made maintaining a routine easier. Being the child of a keyworker parent during lockdown may have been protective for child emotional wellbeing.