title: Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients

abstract:
BackgroundKetamine, and its isomer esketamine are useful for treatment resistant depression (depression not responsive to traditional antidepressants). Compared to other antidepressants, ketamine and esketamine lack a therapeutic delay and do not increase risk of suicidality in adolescents. Esketamine gained FDA approval in March of 2019.

ObjectiveThis study aimed to geographically characterize ketamine and esketamine prescriptions in the United States among Medicaid patients.

MethodsKetamine and esketamine prescription rate data per state per quarter were obtained from the Medicaid State Drug Utilization Database for 2019-2020. Total prescription rates per year for ketamine and esketamine were obtained for 2009-2020.

ResultsBetween 2009-2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine prescriptions in 2019, Montana and Indiana showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine or esketamine in 2019. Since its approval, esketamine prescriptions have surpassed those of ketamine. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. Ten states prescribed neither ketamine or esketamine in 2020.

ConclusionDespite the effectiveness of ketamine and esketamine for treatment resistant depression, their use among Medicaid patients was limited and variable in many areas of the US.

category: psychiatry and clinical psychology


title: Determinants of motivated behavior are linked to fatigue and its perturbation by SARS-CoV-2 vaccination

abstract:
BackgroundFatigue has an adaptive function and serves as a temporary signal to rest and save energy often in response to immune activation. It may, however, also persist in a pathological condition incurring significant burden. While subjective symptoms and scientific consensus indicate that both physical and mental determinants of motivated behavior are affected in fatigue, the underlying processes are rarely examined using objective, task-based indicators.

MethodsIn three consecutive studies, including validation (N = 48) and reliability assessments (N = 27), we use an experimental task to jointly objectify reward learning and effort execution as two determinants of behavioral motivation. In addition, we tested how fatigue and its acute perturbation in response to immune activation after SARS-CoV-2 vaccination are linked to these task-based indicators of motivation in a longitudinal cross-over design (N = 55).

ResultsThe validation study showed the utility of the experimental task for simultaneously assessing learning, effort exertion, and its regulation based on subjective confidence. The reliability assessment over a one-week period indicated that symptoms of fatigue and task behavior are highly reliable and that repetition effects have little impact on motivated behavior. Finally, in the vaccination trial, we found significant links between fatigue and task behavior. Baseline levels of fatigue predicted how effort is gauged in dependence of current confidence about reward outcomes, and state perturbations of fatigue in the context of the SARS-CoV-2 vaccination reduced confidence during learning. Importantly, task success was significantly lower in subjects who reported high fatigue at baseline and who additionally experienced stronger increase in fatigue in response to vaccination.

DiscussionOur results demonstrate that the experimental task allows to jointly assess determinants of motivated behavior, and to link its constituent processes to subjective fatigue. This suggests that our understanding of fatigue and its perturbation due to acute immune activation can benefit from objective, task-based indicators of the underlying motivational mechanisms. Future studies could build on these findings to further deepen the understanding of neurobehavioral mechanisms underlying fatigue in the context of immune activation.


title: Specificity of cortical area and thickness as biomarkers for comorbid internalizing and externalizing mental disorders in pre-adolescence

abstract:
BackgroundComorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical changes represent a simple aggregate of the effects on each disorder, and if comorbidity-related cortical surface changes relate to a distinct genetic underpinning.

MethodsWe studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (Dysthymia, Major Depressive Disorder, Disruptive Mood Dysregulation Disorder, Agoraphobia, Panic Disorder, Specific Phobia, Separation Anxiety Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder, Post-Traumatic Stress Disorder), externalizing diagnostic groups (Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct disorder) a group with comorbidity of the two and a healthy control group. Genome-wide association analysis and cell type specificity analysis were performed on 4,716 unrelated European participants from this cohort.

ResultsReduced cortical surface area but increased thickness occurs across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT changes, while those patient groups without comorbidity had significant thickness increases. Distinct biological pathways were implicated for regional SA and CT changes. Specifically, CT changes were associated with immune-related processes implicating microglia, while SA-related changes related mainly to excitatory neurons.

ConclusionsThe emergence of comorbidity across distinct clusters of psychopathology is unlikely to be a simple additive neurobiological effect. Distinct risk-adaptation processes, with unique genetic and cell-specific factors may underlie SA and CT changes. Children with highest risk but lowest resilience, both captured in their developmental morphometry, develop a comorbid illness pattern.


title: Non-pharmacological measures for the treatment of iron deficiency anemia: A systematic review and meta-analysis

abstract:
ObjectiveTo conduct a systematic review and meta-analysis to evaluate the effectiveness of non-pharmacological measures for the treatment of iron-deficiency anemia (IDA).

Data sourcesMEDLINE (via PubMed), Cochrane library, SciELO/LILACS and EMBASE up to June 2021

Study selection and data extractionWe identified all randomized controlled trials (RCTs) that used non-pharmacological measures to treat IDA including iron pots/ingots, or food use were included. The outcomes of interest were hemoglobin (Hb) concentrations and prevalence of anemia.

Results479 studies were retrieved from the databases, of which 4 duplicate records were removed. After, all titles and abstracts were reviewed, 23 articles were considered potentially relevant, and were read in full and checked for eligibility. Three articles met all inclusion criteria. We also conducted a manual search for citations and a further 8 records were identified and checked for eligibility. Eleven RCTs were included in this review. Estimates showed that the use of non-pharmacological measures was associated with a statistically significant overall increase in mean Hb (MD +0.45 g/dL, 95% CI 0.05 to 0.85, p=0.03). The effect of non-pharmacological measures on the prevalence of IDA was analyzed in only 5 RCTs. Participants in the intervention groups were 2.78 times less likely to suffer from IDA than those in the control groups, OR=2.78, 95% CI 0.93, 8.29, however without significance for the overall effect (p=0.07).

ConclusionNon-pharmacological therapies have a positive effect on iron balance, and can a useful adjunct to programs to prevent and treat IDA in at-risk populations. (PROSPERO registration number CRD42021261773).

category: public and global health


title: Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study.

abstract: The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety ("physio-affective") symptoms three to four months later. The present study was performed to characterize whether the effects of SpO2 and PBT on the physio-affective phenome of Long COVID are mediated by immune, oxidative and nitrosative stress (IO&NS) pathways. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores. Around 60% of the variance in the physio-affective phenome of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Both PBT and SpO2 strongly predict OSTOX/ATIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the physio-affective symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. Post-viral physio-affective symptoms have an inflammatory origin and are partly mediated by neuro-oxidative toxicity.


title: The prevalence of SARS-CoV-2 antibodies within the community of a private tertiary university in the Philippines: a serial cross sectional study

abstract: The antibody testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was used to detect the presence of antibodies in a private university setting. This serial cross-sectional study determined the seroprevalence of SARS-CoV-2 antibodies using qualitative and quantitative tests. Between June 2021 to December 2021, samples from 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021. However, a decreasing trend in IgG reactivity was found in vaccinated individuals over time. IgG antibody formation was observed across all brands of vaccines.


title: A Systematic Review of the Beighton Score Compared with Other Commonly Used Measurement Tools for Assessment and Identification of Generalised Joint Hypermobility (GJH)

abstract: This systematic review compares the validity and reliability of the Beighton Score to those of other commonly used scores for identifying generalised joint hypermobility (GJH). Inclusion criteria: English language, studies on humans, all types of study designs, publications in academic journals, publications from the year two thousand onwards, publications in print and theses. Exclusion criteria: studies not in English, studies measuring single joints only, studies published before the year 2000, cadaveric studies, papers with only abstracts available. An electronic literature search was undertaken of Pub Med/MEDLINE, Embase, Scopus, Cochrane Database, SPORT Discus, Pedro databases, followed by a manual search between August and November 2021. The final review included 73 papers. The PRISMA (2021) COSMIN (2010) guidelines and CASP (2019) criteria were used to evaluate methodological quality and bias. The Beighton Scores intra-rater and inter-rater reliability ranged between ICC 0.74-0.99 and ICC 0.72-0.98 respectively. The BS has reasonable intra-rater and inter-rater reliability, however validity cannot be accurately determined as incorporation bias was identified as a major issue in study methodology, not previously identified in the literature. Paucity of data prevented accurate assessment of other scoring systems. Urgent research is required to clarify these issues and compare the BS to other tests. No source of funding was received in in undertaking this review. The author has no conflict of interests to disclose. This review was not registered. This review has been conducted as closely as possible in accordance with the PRISMA guidelines for reporting systematic reviews.

category: rheumatology


title: Workplace and lifestyle heterogeneity in subjective wellbeing: Latent Class Analysis of UK Time Use Survey before and during COVID-19

abstract:
BackgroundMental health in the UK had deteriorated compared with pre-pandemic trends. The impact of COVID-19 on the subjective wellbeing of working populations with distinct lifestyles is not yet studied.

MethodsCombining time use surveys collected pre- and during COVID-19, latent class analysis was used to identify distinct lifestyles based on aggregated daily activity patterns and reported working modes. We provide qualitative pen portraits alongside pre-versus-during pandemic comparisons of intraday time use and wellbeing patterns. Lifestyle heterogeneity in wellbeing was quantified in relation to aggregated activity types.

ResultsCOVID-19 impact on wellbeing varied significantly between usual working hours (6am-6pm) and rest of the day. The decline in wellbeing outside of usual working hours was significant and consistent across lifestyles. During usual working hours, the direction of impact varied in line with working modes: wellbeing of homeworkers decreased, remained relatively stable for commuters, and increased for certain hybrid workers. Magnitude of impact correlates strongly with lifestyle: those working long and dispersed hours are more sensitive, whereas non-work dominated lifestyles are more resilient.

ConclusionThe direction and magnitude of impact from COVID-19 were not uniformly manifested across activity types, time of day, and latent lifestyles. Blurring work-life boundaries and general anxiety about the pandemic may be key determinants of the decline outside of usual working hours. During usual working hours, strong yet complex correlations between wellbeing and time-use changes suggested that policies aiming to enhance wellbeing of workers need to consider not only spatial flexibility but also provide wider support for temporal flexibility.

What is already knownIn the UK, mental health deteriorated compared with pre-pandemic trends. It is presumed that not everyone was affected equally, but there has been little evidence distinguishing population groups with distinct working modes and lifestyles.

What are the new findingsDirection of COVID-19 impact strongly correlates with working mode and extent of spatial flexibility: wellbeing decreased for homeworkers, but increased for some hybrid workers. Magnitude of COVID-19 impact strongly correlates with lifestyle and extent of temporal flexibility: those working long and dispersed hours more were sensitive, whereas non-work dominated lifestyles were more resilient.

How might this impact policyPolicymakers and employers need to consider the important function workplace has on mental health. As homeworking arrangements become permanent, the psychosocial function of traditional workplaces will become more pertinent. Flexibility around the established work-time regime will also benefit workers mental health, and give them greater control to choose and transition between lifestyles.

category: occupational and environmental health


title: Grandfathers and Grandsons: Social Security Expansion and Child Health in China

abstract: We examine the multigenerational impacts of a nationwide social pension program in China, the New Rural Pension Scheme (NRPS). NRPS was rolled out in full scale since 2012, and rural enrollees over age 60 are eligible to receive a minimum of 70 CNY non-contributory monthly pension. We leverage age eligibility and variations in pension receipt to identify the inter-generational effect of NRPS on health among grandchildren. We find NRPS substantially increases child weight without impacting height. Overall, child BMI z score increases by 1.09, which is largely driven by grandfathers pension receipt raising rates of overweight and obesity among grandsons. Among the potential mechanisms, our findings are more plausibly explained by a mixture of income effect, son preference, and rising inter-generational co-residence and childcare.

category: health economics


title: Systematic searching in Ovid Embase: understanding the MEDLINE document collection and identifying conference records

abstract: Ovid Embase is an important database in systematic searches for health and medical topics. This paper shows how the document collections on Ovid Embase can be used to limit searches and isolate the unique content from MEDLINE that is available on Embase. This is used to test a method for identifying conference records from Embase. The recommended method found 5,108,945 conference records on Embase on Ovid March 1 2022, about 14% of the database. Search strategies are provided for the scenarios that are most likely to be encountered in systematic searches.

category: health informatics


title: Critical Arterial Stenosis Revisited

abstract:
IntroductionStenosis of an organ/tissue primary artery may produce ischemia, malfunction or only reduce blood flow reserve. Despite incomplete hemodynamic understanding of critical arterial stenosis, degree of diameter stenosis continues to be an index for patient management. This study aims to use conservation of energy to; quantitate the arterial pressure gradient produced by stenosis, determine organ/tissue perfusion pressure, blood flow and reserve as a function of degree of diameter stenosis and identify critical diameter stenosis, if it exists.

MethodsA three-component system is considered, parallel stenotic artery and collateral circulation supplying organ/tissue. Energy analysis of arterial stenosis gives the pressure gradient produced and stenosis vascular resistance. Organs/tissues intrinsically autoregulate blood flow when perfusion pressure is greater than threshold value. System energy analysis defines collateral vascular resistance and gives perfusion pressure, blood flow and reserve as a function of diameter stenosis. Renal and internal carotid artery (ICA) stenosis provide numerical examples.

ResultsThe magnitude of stenosis energy dissipation, K, is a fourth power function of stenosis diameter with a steep slope between 65% and 80%, (K = 67 to 625). Systems without collaterals, C = 0, have discrete critical stenosis values within this range. Renal critical stenosis is 74% (K = 233). Systems with poor collaterals, C < 1, have critical stenosis from 65% to 99% depending on collateral magnitude. Critical ICA stenosis begins at 70% and up to 99%, (K = 132 to {infty}). Degree of cerebral ischemia is non-linearly inversely proportional to collateral magnitude,C. Systems with good collateral circulation, C > 1, do not have critical stenosis, including the ICA (cerebral hemisphere). In these systems stenosis progression reduces blood flow reserve but does not produce ischemia.

ConclusionCritical diameter arterial stenosis may or may not exist for specific organ/tissue systems depending on the magnitude of collateral circulation.

category: cardiovascular medicine


title: Effect of two methods of soft tissue augmentation for socket closure on soft tissue landmarks and ridge dimensions- Results from software-based analysis of clinical data

abstract:
PurposeThe aim of this study was to evaluate the effect of connective tissue grafts (CTG) and pediculated connective tissue grafts (P-CTG) for extraction socket closure on soft tissue landmarks and ridge dimensions.

Methods45 subjects were randomized into two groups, where the soft tissue closure of extraction sockets was done by pediculated connective tissue grafts (P-CTG group) and connective tissue grafts (CTG group). On photographs taken at different time-points, four markers corresponding to marginal gingiva (MG), mucogingival junction (MGJ), mesial papilla (MP) and distal papilla (DP) were placed. After image alignment and stacking, the markers were tracked through five photographs taken during the course of the therapy. The displacement, total displacement (TD), divergence and angle of maximum divergence (AMD) for each marker were recorded. Buccolingual and mesiodistal dimensions of edentulous sites were measured, and the difference from the baseline to 6-months in both the dimensions was calculated and was described as buccolingual gain (BL gain) and mesiodistal gain (ML gain) respectively.

ResultsIntergroup comparison of displacement and divergence of markers across both the groups showed varying levels of significance. P-CTG resulted in higher buccolingual dimensions at 3 months (P=0.001) and 6 months (P=0.002) when compared to the CTG group. From baseline to 6-months, the BL and MD gains were 2.82{+/-}1.29mm & 1.68{+/-}1.12mm and 1.27{+/-}0.65mm & 1.48{+/-}0.67mm in P-CTG and CTG group respectively. In the P-CTG group, TD (r=0.4; P=0.001) & AMD (r=0.5; P=0.05) of MG and TD (r=0.2; P=0.005) of MGJ resulted in BL gains. In the CTG group, TD (r=0.7; P=0.004) and AMD (r=0.3; P=0.004) of MP and AMD of MGJ was associated with a significant BL gain.

ConclusionsP-CTG and CTG had significant effects on displacement and divergence of soft tissue landmarks respectively. The relocation of these landmarks, seem to result in an improvement in the buccolingual dimensions of the post-extraction ridge.

category: dentistry and oral medicine


title: Estimating the period prevalence of SARS-CoV-2 infection during the Omicron (BA.1) surge in New York City (NYC), January 1-March 16, 2022

abstract: In a population-based survey of NYC adults, we assessed positive SARS-CoV-2 tests (including via exclusive at-home testing) and possible cases among untested respondents. An estimated 27.4% (95%CI: 22.8%-32.0%) or 1.8 million adults (95%CI: 1.6-2.1 million) had SARS-CoV-2 infection. SARS-CoV-2 prevalence was high among groups that are more vulnerable to severe SARS-CoV-2 and death, including unvaccinated persons (21.7%, 95%CI 9.6%-33.8%) and those aged 65+ (17.8%, 95%CI 10.2-25.4%). Population-based representative surveys are an important adjunct surveillance tool to standard testing-based SARS-CoV-2 surveillance.

category: epidemiology


title: Higher contact among vaccinated can be a mechanism for negative vaccine effectiveness

abstract: Evidence from early observational studies suggested negative vaccine effectiveness for the SARS-CoV-2 Omicron variant. Using transmission modeling, we illustrated how increased contact between vaccinated individuals, vaccinated contact heterogeneity, paired with lower vaccine efficacies could produce negative measurements and how we can identify this mechanism via a key temporal signature.


title: A comparison of different methods for handling measurements affected by medication use

abstract: In epidemiological research it is common to encounter measurements affected by medication use, such as blood pressure lowered by antihypertensive drugs. When one is interested in the relation between the variables not affected by medication, ignoring medication use can cause bias. Several methods have been proposed, but the problem is often ignored or handled with generic methods, such as excluding individuals on medication or adjusting for medication use in the analysis. This study aimed to investigate methods for handling measurements affected by medication use when one is interested in the relation between the unaffected variables and to provide guidance for how to optimally handle the problem. We focused on linear regression and distinguish between the situation where the affected measurement is an exposure, confounder or outcome. In the Netherlands Epidemiology of Obesity study and in several simulated settings, we compared generic and more advanced methods, such as substituting or adding a fixed value to the treated values, regression calibration, censored normal regression, Heckmans treatment model and multiple imputation methods. We found that often-used methods such as adjusting for medication use could result in substantial bias and that methods for handling medication use should be chosen cautiously.


title: Spatially regulated designs of incidence surveys can match the precision of classical survey designs whilst requiring smaller sample sizes: the case of snakebite in Sri Lanka

abstract:
BackgroundSnakebite envenoming is a neglected tropical disease. Data from the worst affected countries are limited because conducting epidemiological surveys is challenging. We assessed the utility of inhibitory geostatistical design with close pairs (ICP) to estimate snakebite incidence.

MethodsThe National Snakebite Survey (NSS) in Sri Lanka adopted a multistage cluster sampling design, based on population distribution, targeting 1% of the countrys population. Using a simulation-based study, we assessed predictive efficiency of ICP against a classical survey design at different fractions of the original sample size of the NSS. We also assessed travel distance, time taken to complete the survey, and sensitivity and specificity for detecting high-risk areas for snake envenoming, when using these methods.

ResultsA classical survey design with 33% of the original NSS sample size was able to yield a similar predictive efficiency. ICP yielded the same at 25% of the NSS sample size, a 25% reduction in sample size compared to a classical survey design. ICP showed >80% sensitivity and specificity for detecting high-risk areas of envenoming when the sampling fraction was >20%. When ICP was adopted with 25% of the original NSS sample size, travel distance was reduced by >40% and time to conduct the survey was reduced by >75%.

ConclusionsThis study showed that snakebite envenoming incidence can be estimated by adopting an ICP design with similar precision at a lower sample size than a classical design. This would substantially save resources and time taken to conduct epidemiological surveys and may be suited for low resource settings.

Key messagesO_LIInhibitory geostatistical design with close pairs (ICP) for incidence surveys can match the precision of classical survey designs at lower sample sizes.
C_LIO_LIThe ICP design showed a lower predictive variance than classical design, indicating ICP designs were able to produce more reliable predictions.
C_LIO_LIThe ICP design showed a lower time to complete the survey than the classical sampling method.
C_LIO_LIAlthough primary sampling units in the ICP design maintain a minimum distance between two units, ICP did not increase travel distance compared to the classical survey design.
C_LIO_LIResource requirements and time to complete surveys can be reduced without increasing the distance to travel by adopting ICP design for epidemiological surveys.
C_LI


title: Is there a higher risk of exposure to Coxiella burnetii for pre-clinical veterinary students?

abstract:
Coxiella burnetii is globally distributed but evidence of zoonotic transmission in the Caribbean region is scarce. The presence of the bacterium is suspected on the Caribbean island of St. Kitts. The risk of exposure of veterinary students was reported in other regions of the world but is not documented in the Caribbean region. The present study aimed to evaluate the risk of exposure to C. burnetii for pre-clinical veterinary students attending an island-based veterinary school. A cross-sectional study was conducted to compare incoming and outgoing veterinary students seroprevalence. Serology was performed using indirect immunofluorescence assay to test Coxiella burnetii Phase I and Phase II immunoglobulins M and G. Background data were gathered using a standardized questionnaire.

Of the 98 participants (48 incomings and 50 outgoings), 41 (41.8 %, 95 %CI: 31.9-52.2) were seropositive to C. burnetii. There was no significant difference between the two groups (45.8% for incoming vs. 38.0% for outgoing) (p=0.4). No risk factors were significantly more reported in the seropositive group. U.S. state of origin of the students was not associated with seropositivity either.

Pre-clinical veterinary students do not have a higher risk of exposure to C. burnetii by attending the veterinary school in St. Kitts, but they are highly exposed before arrival on the island. Most of these participants had experience with animals either through farming or previous veterinary technician employment. This indicates a high exposure in the U.S. young population aiming to become veterinarians. There is an urgent need to increase C. burnetii surveillance in animals and humans to apply relevant prevention and control measures, including recommendations for vaccination of students and professionals at risk.

Author SummaryQ fever is a zoonosis present worldwide. Risk of exposure is higher in livestock farmers and other animal-related professions, including veterinary students. The presence of the bacterium is suspected on the Caribbean island of St. Kitts. We aimed to evaluate the risk of exposure to C. burnetii for students attending an American veterinary school based in St. Kitts. By comparing seroprevalence in incoming and outgoing students, we observed no risk of exposure by attending the school. These findings are different from studies in other veterinary schools. Future studies could explain these geographical differences and inform veterinary schools worldwide on appropriate measures to protect students from exposure to C. burnetii. Moreover, we detected a high seroprevalence in the incoming population, proving an anterior exposure. This indicates a high exposure in the U.S. young population aiming to become veterinarians. There is an urgent need to increase C. burnetii surveillance in animals and humans to apply relevant prevention and control measures, including recommendations of vaccination of students and professionals at risk.


title: Analyses of Omicron genomes from India reveal BA.2 as a more transmissible variant

abstract: This is the first study on omicron genomes from India to focus on phylodynamics and phylogenomics trait to provide an insight into the evolution of omicron variants. We analyzed 564 genomes deposited to GISAID database from various states of India. Pangolin COVID-19 Lineage Assigner tool was used to determine lineage assignment of all retrieved genomes. A Maximum likelihood (MLE) tree construction further confirms the separation of genomes into two distinct clades, BA. 1. and BA. 2. A very high reproduction number (R0) of 2.445 was estimated for the lineage BA.2. The highest R0 value in Telangana confirms the prevalence of lineage BA.2 in the state. Construction of the Reduced Median (RM) network shows evolution of some autochthonous haplogroups and haplotypes, which further supports the rapid evolution of omicron as compared to its previous variants. Phylogenomic analyses using maximum likelihood (ML) and RM show the potential for the emergence of sub-sublineages and novel haplogroups respectively. Due to the recombinant property and high transmissibility of omicron virus, we suggest continuous and more widespread genome sequencing in all states of India to track evolution of SARS-CoV-2 in real time.


title: Health care use attributable to COVID-19: A propensity matched national electronic health records cohort study of 249,390 people in Wales, UK.

abstract:
BackgroundTo determine the extent and nature of changes in infected patients healthcare utilization, we studied healthcare contact in the 1-4 weeks and 5-24 weeks following a COVID-19 diagnosis compared to propensity matched controls.

MethodsSurvival analysis was used for time to death and first clinical outcomes including clinical terminology concepts for post-viral illness, fatigue, embolism, respiratory conditions, mental and developmental conditions, fit note, or hospital attendance. Increased instantaneous risk for the occurrence of an outcome for positive individuals was quantified using hazard ratios (HR) from Cox Regression and absolute risk was quantified using relative risk (RR) from life table analysis.

ResultsCompared to matched individuals testing negative, surviving positive community-tested patients had a higher risk of post-viral illness (HR: 4.57, 95%CI: 1.77-11.80, p=0.002), fatigue (HR: 1.47, 95%CI: 1.24-1.75, p<0.001) and embolism (HR: 1.51, 95%CI: 1.13-2.02, p=0.005) at 5-24 weeks post-diagnosis. In the four weeks after COVID-19 higher rates of sick notes were being issued for community-tested (HR: 3.04, 95%CI: 0.88 to 10.50, p<0.079); the risk was reduced after four weeks, compared to controls. Overall healthcare attendance for anxiety, depression was less likely in those with COVID-19 in the first four weeks (HR: 0.83, 95%CI: 0.73-1.06, p=0.007). After four weeks, anxiety, depression is less likely to occur for the positive community-tested individuals (HR: 0.87, 95%CI: 0.77-1.00, p=0.048), but more likely for positive hospital-tested individuals (HR: 1.16, 95%CI: 1.00-1.45, p=0.053). Although statistical associations between positive infection and post-infection healthcare use are clear, the absolute use of healthcare is very.

ConclusionsCommunity COVID-19 disease is associated with increased risks of post-viral illness, fatigue, embolism, depression, anxiety and respiratory conditions. Despite these elevated risks, the absolute healthcare burden is low. Either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare.

Trial registrationData held in SAIL databank are anonymised and therefore, no ethical approval is required. All data in SAIL has the permission from the relevant Caldicott Guardian or Data Protection Officer and SAIL-related projects are required to obtain Information Governance Review Panel (IGRP) approval. The IGRP approval number for this study is 1259.


title: Uncovering the linguistic characteristics of psychotherapy: a computational approach to measure therapist language timing, responsiveness, and consistency

abstract: Although individual psychotherapy is generally effective for a range of mental health conditions, little is known about the moment-to-moment language use of effective therapists. Increased access to computational power, coupled with a rise in computer-mediated communication (telehealth), makes feasible the large-scale analyses of language use during psychotherapy. Transparent methodological approaches are lacking, however. Here we present novel methods to increase the efficiency of efforts to examine language use in psychotherapy. We evaluate three important aspects of therapist language use - timing, responsiveness, and consistency - across five clinically relevant language domains: pronouns, time orientation, emotional polarity, therapist tactics, and paralinguistic style. We find therapist language is dynamic within sessions, responds to patient language, and relates to patient symptom diagnosis but not symptom severity. Our results demonstrate that analyzing therapist language at scale is feasible and may help answer longstanding questions about specific behaviors of effective therapists.


title: Precise Language Responses Challenge Easy Rating Scales - Comparing Clinicians and Respondents Views

abstract:
BackgroundClosed-ended rating scales are the most used response format for researchers and clinicians to quantify mental states, whereas in natural contexts people communicate with natural language. The reason for using such scales is that they are typically argued to be more precise in measuring mental constructs, whereas the respondents views as to what best communicates mental states are frequently ignored.

MethodsWe assessed respondents (N = 304) degree of depression using rating scales, descriptive words, selected words, and free text responses and probed the respondents and clinicians (N = 40) for their attitudes to the response formats across twelve dimensions related to the precision of communicating their mental states and the ease of responding.

ResultsRespondents found free text to be more precise (e.g., precision d = .88, elaboration d = 2.0) than rating scales, whereas rating scales were rated as easier to respond to (e.g., easier d = - .67, faster d = -1.13). Respondents preferred the free text responses to a greater degree than rating scales compared to clinicians.

ConclusionsThese finding supports the idea that future assessment of mental health can be aided by computational method based on text data.


title: Does living in major towns favor institutional delivery in Somalia?

abstract:
BackgroundAn institutional delivery is a childbirth that takes place at a health facility in which the birth is assisted by a skilled healthcare provider. Institutional delivery could reduce approximately 33% of maternal deaths. However, the use of institutional healthcare is failing in many Sub-Saharan African countries because of many factors, including poverty, a lack of access, distance, a lack of transport and other socio-cultural factors. In Somalia, only 32% of births are delivered in a health facility with the assistance of a skilled healthcare provider. We aim to investigate the factors hindering women from giving birth at health facilities in major towns in Somalia, where most of the health facilities in the country are concentrated.

MethodsA community-based health survey was carried out from 11 major towns in Somalia between October and December 2021. A structured and pretested questionnaire was used to collect data from 430 women who gave birth last five years. A logistic regression analysis was carried out to establish the association between the covariates of interest and the outcome variable.

ResultsThe overall prevalence of institutional delivery was 57%. Approximately 38% of women who live in Mogadishu and 53% of women living in another ten towns give birth at home. Women who had a poor knowledge of the importance of health facility delivery had nearly four times higher odds of delivering at home (OR 3.645 CI: 1.488-8.928). Similarly, those who did not receive antenatal care (OR 2.551, CI: 1.017-6.399), and those who did not receive a consultation on the place of delivery (OR 2.145, CI: 1.167-3.942) were more likely to give birth at home. The reasons for home delivery included financial reasons, must use transport to reach the nearest health facility and it is easier to deliver at home.

ConclusionThe study shows that home delivery is high in major towns in Somalia. It is important for health providers to communicate with women and men about the risks related to pregnancy and educate them about the importance of a health facility delivery. Antenatal care should be considered universal for pregnant women, while central and federal governments should guarantee access to free and within-reach ANC for women and girls. In conflict settings in Somalia, this should be done by training community health workers and auxiliary nurses who provide ANC for women through home visits.


title: Immediate, remote smoking cessation intervention in participants undergoing a targeted lung health check: QuLIT2 a randomised controlled trial.

abstract:
BackgroundLung cancer screening programs provide an opportunity to support smokers to quit, but the most appropriate model for delivery remains to be determined. Immediate face to face smoking cessation support for people undergoing screening can increase quit rates, but it is not known whether remote delivery of immediate smoking cessation counselling and pharmacotherapy in this context is also effective.

Materials and MethodsIn a single-blind randomised controlled trial, smokers aged 55-75 years attending a Targeted Lung Health Check (TLHC) were allocated by day of attendance to receive either immediate telephone smoking cessation support (TSI) (starting immediately and lasting for 6 weeks) with appropriate pharmacotherapy, or usual care (very brief advice to quit and signposting to smoking cessation services) (UC). The primary outcome was self-reported 7-day point prevalence smoking abstinence at three months. Differences between groups were assessed using logistic regression.

Results315 current smokers taking part in the screening programme, mean (SD) age 63(5.4) years, 48% female, were randomised to telephone smoking cessation (n=152) or usual care (n=163). The two groups were well-matched at baseline. Self-reported quit rates were higher in the intervention arm, 21.1% vs 8.9% (odds ratio [OR]: 2.83, 95% CI 1.44-5.61, p=0.002). Controlling for participant demographics, baseline smoking characteristics or the discovery of abnormalities on low dose CT scanning did not modify the effect of the intervention.

ConclusionImmediate provision of an intensive telephone-based smoking cessation intervention, delivered within a targeted lung screening context, is associated with increased smoking abstinence at three months.

Trial registrationThis study is registered online: ISRCTN12455871.

Take home messageProviding immediate, telephone smoking cessation support with pharmacotherapy to smokers enrolled in a TLHC program increases quit rates in this population by almost a third.

category: respiratory medicine


title: Barriers and facilitators to the implementation of cell phone interventions to improve the use of family planning services among women in Sub-Saharan Africa: a systematic review

abstract:
BackgroundMobile health (mHealth) interventions are being tested to improve contraceptive uptake in SubSaharan Africa (SSA). However, few attempts have systematically reviewed the mHealth programs aiming to improve family planning (FP) services among women in SSA. This review identifies and highlights facilitators and barriers to implementing cell phone interventions designed to target women FP services.

MethodsDatabases including PubMed, CINAHL, Epistemonikos, Embase, and Global Health were systematically searched for studies from January 01, 2010, to December 31, 2020, to identify various mHealth interventions used to improve the use of FP services among women in SSA. Two authors independently selected eligible publications based on inclusion/exclusion criteria, assessed study quality and extracted data using a pre-defined data extraction sheet. In addition, a content analysis was conducted using a validated extraction grid with a pre-established categorization of barriers and facilitators.

ResultsThe search strategy led to a total of 8,188 potentially relevant papers, of which 16 met the inclusion criteria. The majority of included studies evaluated the impact of mHealth interventions on FP services; access (n = 9) and use of FP outcomes (n = 6). The most-reported cell phone use was for women reproductive health education, contraceptive knowledge and use. Barriers and facilitators of the use of mhealth were categorized into three main outcomes: behavioral outcomes, data collection and reporting, and health outcomes. mHealth interventions addressed barriers related to provider prejudice, stigmatization, discrimination, lack of privacy, and confidentiality. The studies also identified barriers to uptake of mHealth interventions for FP services, including decreased technological literacy and lower linguistic competency.

ConclusionThe review provides detailed information about the implementation of mobile phones at different healthcare system levels to improve FP services; outcomes. Barriers to uptake mHealth interventions must be adequately addressed to increase the potential use of mobile phones to improve access to sexual reproductive health awareness and family planning services.

Systematic review registrationPROSPERO CRD42020220669 (December 14, 2020)

category: sexual and reproductive health


title: Hospitalized patients with severe COVID-19 during the Omicron wave in Israel - benefits of a fourth vaccine dose

abstract:
ImportanceWaning immunity against COVID-19 in parallel with an increased incidence during the Omicron outbreak led the Israeli Ministry of Health to recommend a second booster dose of BNT162b2 (Pfizer) to high-risk individuals. Israel was the first country to recommend this, allowing evaluation of the added protection of a fourth vaccine dose to hospitalized patients with severe diseases.

ObjectiveTo assess the effect of a fourth dose for hospitalized patients with severe/critical breakthrough COVID-19.

DesignA cohort study of hospitalized adults from 01/15/2022-01/31/2022.

SettingsA multi-center study of 14 medical centers in Israel.

ParticipantsHospitalized adult patients with PCR-confirmed severe/critical COVID-19. Excluded were patients lacking data on vaccination status.

ExposureCases were divided according to the total number of vaccine doses received up to 7 days before diagnosis. Unvaccinated adults and single-dose recipients were grouped into an unvaccinated group.

Main OutcomeA composite of mechanical-ventilation or in-hospital death was defined as poor outcome. Outcomes were compared between 3- and 4-dose vaccinees.

ResultsIncluded were 1,049 patients with severe/critical COVID-19, median age 80 (IQR 69-87), 51% males. Among them, 360 unvaccinated, 34, 172, 386 and 88 were after 1, 2, 3 or 4 doses, respectively. Patients after 3 doses were older, had more males and immunosuppression, but with similar outcomes, 49% vs. 51% compared to unvaccinated patients (p=0.72). Patients after 4 doses were similarly older and immunosuppressed, but had improved outcomes compared to unvaccinated patients, 34% vs. 51% (p<0.01). We proceeded to examine independent predictors for poor outcome in fully-vaccinated patients with either 3 doses given a median of 161 (IQR 147-168) days earlier, or 4 doses given a median of 14 (IQR 10-18) days before diagnoses. Receipt of the fourth dose conferred significant protection: OR 0.51 (95%CI 0.30.87).

Conclusion and RelevanceWithin a population of hospitalized patients with severe/critical breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death, compared to fully vaccinated single-boosted individuals.

Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the benefit of a fourth vaccine dose (second booster) for hospitalized patients with severe COVID-19?

FindingsIn this multicenter cohort study in Israel during the Omicron wave, hospitalized severe COVID-19 patients that received a recent fourth dose had a 49% lower odds for a poor outcome (mechanical ventilation or death) compared with those who received 3 doses approximately 5 months before diagnosis, a significant difference.

MeaningA vaccine booster given at the onset of a COVID-19 wave can benefit vulnerable individuals.

category: infectious diseases


title: The impact of COVID-19 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis

abstract:
ObjectiveThis systematic review and meta-analysis aimed to quantitatively evaluate the effect of the COVID-19 pandemic on respiratory syncytial virus (RSV) associated bronchiolitis among hospitalised infants.

MethodsThe study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on PRISMA guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesise the pooled proportion of infants having RSV- associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI).

ResultsThe eight qualified studies for the meta-analysis were from Spain, Italy, France and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73-22.43%). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20 % (95% CI 12.01-27.59%).

ConclusionThere was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.

What is already known on this topicThe epidemiology of RSV infection which accounts for most bronchiolitis and viral pneumonias in infants was changed during the COVID-19 pandemic. During the spring or summer seasons, a resurgence in RSV positivity among bronchiolitis cases was noted globally during the COVID-19 pandemic.

What this study addsIn spite of reporting lower number of bronchiolitis cases, more number of RSV associated bronchiolitis cases were detected among infants during the COVID-19 pandemic. Meanwhile, countries perceiving a very low number of RSV cases are at an increased risk of resurgence of RSV activity, mainly among older RSV-naive children.

How this study might affect research, practice or policyMonitoring the effect of COVID-19 on RSV activity in infants is essential and regular sentinel surveillance of RSV must be carried out along with influenza and SARS-CoV-2 viruses to minimise the burden of hospitalisation and mortality. Health care professionals and hospitals must be prepared to tackle the rising number of paediatric RSV cases throughout the year. This review also emphasises the importance of promoting RSV maternal vaccines and passive childhood immunisation with monoclonal antibodies (mAbs).


title: Effects of the introduction of interprofessional conferences on the intensive care unit: Comparison of the length of stay in the intensive care unit before and after the introduction of interprofessional conferences

abstract: Recently, interprofessional team medicine has been practiced to achieve medical safety and improve patient outcomes. This study evaluated the effects of interprofessional conferences on intensive care units (ICUs) by comparing outcomes before and after their introduction. This study was conducted at a single center and included 1,765 patients who were admitted to the ICU between April 2017 and March 2019. There were 898 patients in the group before the introduction of conferences (before group) and 867 patients in the group after the introduction of conferences (after group). The interprofessional conferences involved physicians, nurses, physical therapists, nutritionists, and pharmacists. Data were extracted from the medical records. The primary outcome measure was the ICU length of stay (LOS). The secondary outcome measures were hospital LOS and rehabilitation and nutrition started within 48 hours of ICU admission. These outcomes were compared before and after the introduction of interprofessional conferences. The adjusted variables were gender, age, body mass index, ICU readmission, outcome, Barthel index at admission, and disease (classified by the International Statistical Classification of Diseases and Related Health Problems 10th edition). The ICU LOS (regression coefficient: -0.08; 95% confidence interval [CI]: -0.13 to -0.04) and hospital LOS (regression coefficient: -2.96; 95% CI: -5.20 to -0.72) were significantly shorter in after group than in the before group. Moreover, the proportion of patients who commenced nutrition (odds ratio [OR]: 1.45; 95% CI: 1.14 to 1.84) and rehabilitation (OR: 0.77; 95% CI: 0.51 to 1.17) within 48 hours of ICU admission was significantly higher in the after group than in the before group. Interprofessional conferences effectively reduced the ICU LOS and hospital LOS and improved the likelihood of commencing nutrition and rehabilitation within 48 hours of ICU admission.

category: intensive care and critical care medicine


title: The Association of Marital/Partner Status with Patient-Reported Health Outcomes Following Acute Myocardial Infarction or Stroke: Protocol for a Systematic Review and Meta-analysis

abstract:
IntroductionMarital/Partner support is associated with lower mortality and morbidity following acute myocardial infarction (AMI) and stroke. Despite an increasing focus on the effect of patient-centered factors on health outcomes, little is known about the impact of marital/partner status on patient-reported outcome measures (PROMs).

ObjectiveTo synthesize evidence of the association between marital/partner status and PROMs after AMI and stroke and to determine whether associations differ by sex.

Methods and analysisWe will search MEDLINE (via Ovid), Web of Science Core Collection (as licensed by Yale University), Scopus, EMBASE (via Ovid), and PsycINFO (via Ovid) from inception to January 10, 2022. Two authors will independently screen titles, abstracts, and then full texts as appropriate, extract data, and assess risk of bias. Conflicts will be resolved by discussion with a third reviewer. The primary outcomes will be the associations between marital/partner status and PROMs. Meta-analysis will be conducted if appropriate. Subgroup analysis by sex and meta-regression with a covariate for the proportion of male participants will be performed to explore differences by sex.

Ethics and disseminationThis research is exempt from ethics approval because the study will be conducted using published data. We will disseminate the results of the analysis in a related peer-reviewed journal.

PROSPERO registration numberCRD42022295975


title: A Prospective Study to Improve Automated Blood Culture Diagnostics in Gram Negative Sepsis by Implementing a "Diagnostic Stewardship Care-Bundle"

abstract:
ObjectivesWe implemented a diagnostic stewardship care-bundle (DSB): "Sepsis-48" with the aim of evaluating its impact on changes in duration of key steps in automated blood culture diagnostics (aBCD), compliance to care-bundle and turnaround time (TAT).

MethodsIn this prospective study, a care-bundle checklist for automated blood culture bottles (BCBs) received from adult intensive care units (AICUs) was implemented between July 2020-June 2021 (intervention period, P2) and compared with a retrospective, pre-intervention period (P1) between March-June 2020. Microbial identification in positive BCBs with gram-negatives (+nBCBs) was enabled by inoculating conventional biochemical tests directly (dID) and direct antimicrobial susceptibility testing (dAST) was done as per EUCAST RAST standard. Clinical reports were issued only if a RAST reportable gram-negative was identified in dID.

ResultsWe observed significant reductions in the Loading time (LT) [63.5 (104.5-24.5) vs 32 (55-14) minutes, P<0.001] & time to dID+dAST performance (TTD) [186 (288.25-202.25) vs 115 (180-68) minutes, P=0.0018] in +nBCBs received from AICUs during P2. There was a significant increase in compliance to the bundle targets [LT[≤]45: 44% vs 66%, P=.006 and TTD[≤]120: 34% vs 51.7%, P=.03] during P2 (Table 2). Using dID+dAST method, provisional results could be read [~]13 hours earlier than those generated by VITEK(R). Similar improvements were also noted for +nBCBs received from other locations.

O_TBL View this table:
org.highwire.dtl.DTLVardef@1da2dceorg.highwire.dtl.DTLVardef@f5367corg.highwire.dtl.DTLVardef@cc3fcdorg.highwire.dtl.DTLVardef@170be9aorg.highwire.dtl.DTLVardef@f1a063_HPS_FORMAT_FIGEXP  M_TBL O_FLOATNOTable 2:C_FLOATNO O_TABLECAPTIONPerformance and interpretation of direct microbial identification (dID) method by directly inoculating conventional biochemical tests

C_TABLECAPTION C_TBL ConclusionsThe "diagnostic stewardship care-bundle" strategy to improve aBCD was successfully implemented leading to significant reductions in duration of targeted steps. Laboratories should implement "diagnostic stewardship care-bundles" as per their needs to improve microbiological diagnostics.


title: Does greater longevity come with lower life disparity in India? A comparative study between Kerala and Delhi

abstract:
BackgroundLife expectancy and life disparity are two important measures for determining societys health condition. Over last decades, Indian life expectancy has increased, reaching 69.4 years in 2018, with highest life expectancies being registered in Kerala and Delhi, with 75.3 years for both-sexes. Delhi has overtaken Kerala and is now top-ranking state in life expectancy. However, whether Delhi also has a lower disparity than Kerala is still unknown.

ObjectivesTo assess age-at death distributions, trends in life expectancy and life disparity for Delhi and Kerala from 2010-2018; to assess patterns of life disparity and their relation to rising longevity; to show that, despite having similar life expectancies, life disparity varies between Delhi and Kerala.

MethodsAbridged-life table from Sample Registration System from 2010-18 for Kerala and Delhi. Decomposition approach is performed to calculate age-specific contribution to changes in life expectancy and life disparity for each population.

ResultsKerala showed inverse relationship between life expectancy and life disparity but not Delhi. Despite having a better Delhis life expectancy than Kerala during the study period, Delhis life disparity is still higher than Keralas. Disparities in life expectancy and life disparity between the two groups are closely related to their differences in age-specific mortality.

ConclusionsGiven the ongoing demographic transition in India and spatial variations in it, this study is a welcome contribution to our understanding of Indias mortality decline. Our study has revealed that the life disparity in Delhi is higher than that in Kerala. This is because infant mortality in Delhi is higher than in Kerala whereas old age mortality is higher in Kerala than in Delhi.

ContributionBeneficial in allocating healthcare resources to minimize both infants and old deaths and to attain equality in longevity and health.

category: health policy


title: Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium

abstract:
IntroductionTimely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes.

MethodsThe International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEAs 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys.

ResultsThe survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposis sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate.

ConclusionIeDEAs approach for site survey development approach has broad relevance for HIV research networks and other priority health conditions.

category: health systems and quality improvement


title: High sensitivity of a novel rapid test for the diagnosis of clinical and subclinical Plasmodium falciparum infections in a high transmission setting in Burundi

abstract: Rapid diagnostic tests (RDTs) are a key tool for the diagnosis of malaria infections among febrile and subclinical individuals. Low-density infections, and deletions of the P. falciparum hrp2/3 genes (encoding for the HRP2 and HRP3 proteins detected by many RDTs) present challenges for RDT-based diagnosis. The novel Rapigen Biocredit three-band Plasmodium falciparum HRP2/LDH RDT was evaluated among 444 febrile and 468 subclinical individuals in a high transmission setting in Burundi. Results were compared to the AccessBio CareStart HRP2 RDT, and qPCR with a sensitivity of <0.1 parasites/{micro}L blood. Sensitivity among clinical patients was 80.0% (250/313, either of HRP2/LDH positive), compared to 73.2% (229/313) for CareStart (P=0.048). Among subclinical infections, sensitivity was 72.3% (162/224) compared to 58.5% (131/224) for CareStart (P=0.003), and reached 88.3% (53/60) in children <15 years. No (0/362) hrp2 and 2/366 hrp3 deletions were observed. In conclusion, the novel RDT showed improved sensitivity for the diagnosis of P. falciparum.


title: Observed strong pervasive positive selection in the N-terminal domain, receptor-binding domain and furin-cleavage sites of SARS-CoV-2 Spike protein sampled from Zimbabwean COVID-19 patients.

abstract: Mutations primarily in the Spike (S) gene resulted in the emergence of many SARS-CoV-2 variants like Alpha, Beta, Delta and Omicron variants. This has also caused a number of COVID-19 pandemic waves which have impacted human lives in different ways due to restriction measures put in place to curb the spread of the virus. In this study, evolutionary patterns found in SARS-CoV-2 sequences of samples collected from Zimbabwean COVID-19 patients were investigated. High coverage SARS-CoV-2 whole genome sequences were downloaded from the GISAID database along with the GISAID S gene reference sequence. Biopython, NumPy and Pandas Data Science packages were used to load, slice and clean whole genome sequences outputting a fasta file with approximate Spike (S) gene sequences. Alignment of sliced dataset with GISAID reference sequence was done using Jalview 2.11.1.3 to find exact sequences of SARS-CoV-2 S gene. Evidence of recombination signals was investigated using RDP 4.1 and pervasive selection in the S gene was investigated using FUBAR algorithm hosted on the Datamonkey webserver. Matplotlib and Seaborn Python packages were used for Data Visualisation. A plot of Bayes factor hypothesizing non-synonymous substitution being greater than synonymous substitution ({beta} > ) in the S protein sites showed 3 peaks with evidence of strong divergence. These 3 diverging S protein sites were found to be D142G, D614G and P681R. No evidence of recombination was detected by 9 methods of RDP which use different approaches to detect recombination signals. This study is useful in guiding drug, vaccine and diagnostic innovations toward better control of the pandemic. Additionally, this study can guide other non-biological interventions as we better understand the changes in various viral characteristics driven by the observed evolutionary patterns.


title: Mobile Primary Healthcare for post-COVID Patients in Rural Areas: a Proof-of-Concept Study

abstract:
IntroductionPost-COVID syndrome is increasingly recognized as a new clinical entity after SARS-CoV-2 infection. Patients living in rural areas may have to travel long with subjectively great effort to be examined using all necessary interdisciplinary tools. This problem could be addressed with mobile outpatient clinics.

MethodsIn this prospective observational study, we investigated physical fitness, fatigue, depression, cognitive dysfunction and dyspnea in patients with post-COVID syndrome in a mobile interdisciplinary post-COVID outpatient clinic. Upon referral from their primary care physician, patients were offered an appointment at a mobile post-COVID outpatient clinic close to their home.

ResultsWe studied 125 patients (female, n=79; 63.2%) in our mobile unit. All patients reported symptoms lasting for more than 12 weeks after acute infection. 88.3% and 64.1% of patients reported significant impairment in physical and mental quality of life. Patients reported a median of three symptoms. The most frequently reported symptoms were fatigue (86.4%), cognitive dysfunction (85.6%), and dyspnea (37.6%). 56.0% of patients performed at <2.5th percentile at the 1 min sit-to-stand test compared to age and sex-matched healthy controls and 25 patients (20.0%) exhibited a drop in oxygen saturation. A questionnaire given to each patient regarding the mobile unit revealed a very high level of patient satisfaction.

ConclusionThere is an increasing need for high-quality and locally available care for patients with post-COVID syndrome. A mobile post-COVID outpatient clinic is a new concept that may be particularly suitable for use in rural regions. Patients satisfaction following visits in such units is very high.


title: Non-inferiority of essential medicines for caries arrest and prevention in a school-based program: Results from the CariedAway pragmatic clinical trial

abstract:
BackgroundDental caries is the most common global childhood disease. To control caries, the Centers for Disease Control and Prevention recommends school-based caries prevention, and the World Health Organization lists glass ionomer cement and silver diamine fluoride as essential dental medicines. The CariedAway trial tested the comparative effectiveness of these essential medicines when used in a school-based dental care program.

MethodsThis cluster-randomized non-inferiority pragmatic trial was conducted in children from 2018 to 2022. Subjects were randomized at the school level to receive either silver diamine fluoride ("simple care") or an active comparator of glass ionomer sealants and atraumatic restorations ("complex care"). All subjects received tooth brushes, fluoride toothpaste, and fluoride varnish. We assessed caries arrest and incidence at two years using mixed-effects multilevel models and two-sample proportion tests with clustering adjustment.

Results1398 subjects received treatment and completed follow-up observations after two years. The proportion of subjects with arrested caries in simple and complex groups was 0.56 and 0.46, respectively (difference = -0.11, 95% CI = -0.22, 0.01). Prevention rates for no new caries were 0.81 and 0.82 (difference = 0.01, 95% CI = -0.04, 0.06).

ConclusionsOver a two-year, non-intervention period, simple care was non-inferior to complex care for both caries arrest and prevention. Results support the utilization of silver diamine fluoride as an arresting and preventive agent in school-based oral health programs and questions the periodicity of current caries prevention recommendations.


title: Muscle pathology of antisynthetase syndrome according to antibody subtypes

abstract:
Antisynthetase syndrome is recently recognized as one of the major entities of autoimmune myositis. The prototype of antisynthetase syndrome is anti-Jo-1 antibody associated syndrome while the syndromes associated with non-Jo-1 antisynthetase antibodies are clinically and pathologically less recognized. Identifying a non-Jo-1 antisynthetase syndrome patient could be challenging because the full panel serology test may not be available at the time of diagnosis in addition to technical difficulty especially for anti-OJ antibody detection. This study aimed to characterize the muscle pathology and explore the utility of myofiber HLA-DR expression for the diagnosis of antisynthetase syndrome.

We retrospectively compared 212 muscle biopsies from antisynthetase syndrome patients regarding four pathology domains and histology of interests using t test and Fishers exact test as appropriate. We further compared the myofiber HLA-DR expression pattern in antisynthetase syndrome with 602 muscle biopsies with other autoimmune myositis and 140 muscle biopsies with other myopathies potentially containing myositis-like pathology and calculated sensitivity, specificity, positive predictive value, and negative predictive value to identify the most diagnostic pattern for antisynthetase syndrome.

The most common myopathological pattern in antisynthetase syndrome was necrotizing myopathy (46.2%). Perifascular necrosis was present in 28.3% of antisynthetase syndrome. Anti-OJ and anti-EJ antisynthetase syndrome were associated with high muscle fiber scores. Anti-OJ also showed high inflammatory domain score. If muscle biopsies suspicious for dermatomyositis by sarcoplasmic myxovirus resistance protein A immunohistochemical expression and those with inclusion body myositis clinicopathology were excluded, myofiber HLA-DR expression was the most diagnostic of antisynthetase syndrome with 95.4% specificity, 61.2% sensitivity, 85.9% positive predictive value, and 84.2% negative predictive value. HLA-DR expression in perifascicular fibers was highly specific to anti-Jo-1 antisynthetase syndrome.

Anti-OJ antisynthetase syndrome has more prominent myopathology than the other antisynthetase syndrome subtypes. Presence of myofiber HLA-DR expression in a clinicopathologically approved non-dermatomyositis and non-inclusion body myositis muscle biopsy is highly indicative of antisynthetase syndrome. Presence of HLA-DR expression suggests the involvement of type II interferon in the pathogenesis in antisynthetase syndrome subpopulation although the detailed mechanism and the reason for preferential perifascicular localization are yet to be identified.

category: pathology


title: Optimizing multi-domain hematologic biomarkers and clinical features for the differential diagnosis of unipolar depression and bipolar depression

abstract:
There is a lack of objective features for the differential diagnosis of unipolar and bipolar depression, especially those that can be easily accessible in practical settings. Some studies have shown that unipolar and bipolar depression have different associations with hematologic biomarkers and clinical features such as the age of onset. However, none of them have used these features for differential diagnosis. We investigated whether biomarkers of complete blood count, blood biochemical markers and clinical features could accurately classify unipolar and bipolar depression using machine learning methods.

1,160 eligible patients were included in this retrospective study (918 with unipolar depression and 242 with bipolar depression). 27 biomarkers of complete blood count,17 blood biochemical markers and 2 clinical features were investigated for the classification. Patient data was split into training (85%) and test set (15%). Using ten-fold cross validation for training, logistic regression (LR), support vector machine (SVM), random forest (RF) and Extreme Gradient Boosting (XGBoost) were compared with feature selection.

We calculated the AUC, sensitivity, specificity and accuracy. The optimal performance was achieved by XGBoost using a combination of selected biomarkers of complete blood count (WBC, PLR, MONO, LYMPH, NEUT Ratio, MCHC, BASO Ratio, LYMPH Ratio), blood biochemical markers (albumin, potassium, chlorine, HCT, calcium, LDL, HDL) and clinical features (disease duration, age of onset). The optimal performances achieved on the open test set were AUC 0.889, sensitivity 0.831, specificity 0.839 and accuracy 0.863. Hematologic biomarkers and onset features seem to be reliable information that could be easily accessible in clinical settings to improve diagnostic accuracy. In addition, we further analyzed the importance of specific blood biomarkers in samples of disease durations <= 3 years and > 3 years. WBC and MONO remained informative across different disease durations. Meanwhile, NEUT, BASO Ratio, HCT and LYMPH, and albumin were more indicative in the short course (<= 3 years), whereas NLR and chlorine were more indicative in the longer course (> 3 years). This may suggest that, given the overall stability of the model, longitudinal changes in biomarkers should be investigated across different disease courses and age groups.


title: AI-VDT can Help in Detecting Primary Lung Cancer

abstract: The current study shows that measuring volume doubling time could accelerate the detection of primary lung cancer in chest CT imaging. Thirty tumors were selected from surgical cases of primary lung cancer at a university hospital in Japan, and the CT scan data and radiology reports were extracted retrospectively. The CT scan data were processed by a commercial pulmonary nodule AI and volume doubling time was calculated for each historical study time point. 43% of the 30 tumors had an VDT below 400 days in earlier study than the tumor was reported as a nodule on the radiology report. The average days of earlier detection was 299 days. Interpolation of the detailed mortality reduction data from the NELSON study predicted a 5.6% reduction in 10-year mortality from lung cancer.

category: radiology and imaging


title: Fibroblast Growth Factor-23 and Risk of Cardiovascular Diseases: a Mendelian Randomisation study

abstract: Fibroblast growth factor 23 (FGF-23) is associated with a range of cardiovascular and non-cardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomisation approaches can help control for such confounding. SCALLOP consortium data on 19,195 participants were used to generate an FGF-23 genetic score. Data from 337,448 UK Biobank participants were used to estimate associations between higher genetically-predicted FGF-23 concentration and the odds of any atherosclerotic cardiovascular disease (n=26,266 events), of any non-atherosclerotic cardiovascular disease (n=12,652), and of non-cardiovascular diseases previously linked to FGF-23. Measurements of carotid intima-media thickness (CIMT) and left ventricular mass (LVM) were available in a subset. Associations with cardiovascular outcomes were also tested in three large case-control consortia: CARDIOGRAMplusC4D (coronary artery disease, n=181,249 cases), MEGASTROKE (stroke, n=34,217), and HERMES (heart failure, n=47,309). We identified 34 independent variants for circulating FGF-23 which formed a validated genetic score. There were no associations between genetically-predicted FGF-23 and any of the cardiovascular or non-cardiovascular outcomes. In UK Biobank, the odds ratio for any atherosclerotic cardiovascular disease per 1-SD higher genetically-predicted logFGF-23 was 1.03 (95% confidence interval [CI] 0.98-1.08), and for any non-atherosclerotic cardiovascular disease was 1.01 (0.94-1.09). The odds ratios in the case-control consortia were 1.00 (0.97-1.03) for coronary artery disease, 1.01 (0.95-1.07) for stroke, and 1.00 (0.95-1.05) for heart failure. In those with imaging, logFGF-23 was not associated with CIMT or LVM index. This suggests that previously reported observational associations of FGF-23 with risk of atherosclerotic and non-atherosclerotic cardiovascular diseases are unlikely to be causal.

category: nephrology


title: Predictors of Survival among 6-59 Months Old Children with Severe Acute Malnutrition: A Retrospective Cohort

abstract:
BackgroundUndernutrition among children is a significant contributor to the global disease burden and a leading cause of child mortality. Ethiopia, home to more than 16 million children under 5 years old, is one of the countries that have high levels of wasting. The aim of this study was to assess survival status and predictors of mortality among children with severe acute malnutrition admitted to Dubti Zonal Referral hospital from January 1/2017 to September 30/2019.

MethodsFacility-based retrospective cohort was conducted among 331 severely acutely malnourished children. Data were collected from SAM management registration, individual patient cards and multi-charts admitted from January 1/2017 to September 30/2019. Cox-regression was used to characterize survival within the cohort and to estimate the effect of specific variables while controlling for potential confounders. The hazard ratio was used as a measure of the outcome. P-value less than 0.05 was considered statistically significant to identify independent predictors in multivariable analysis.

ResultThe median age of study participants was 18 months and males were 187(56%). About half of 160 (48.3%) respondents were with co-morbidities during admission: diarrhea (44%) and pneumonia (26%) were the major co-morbidities. From a total of 331 SAM children, 255(77%) were recovered, 34(10%) died, and 40(12%) have defaulted from treatment. The main risk factors for earlier death of severely malnourished children were rural residence (AHR=1.6, 95% CI= 0.745-3.493), being on IV Infusion (AHR=2.5, 95% CI= 1.12-4.18), anemia during admission (AHR= 6.27, 95% CI =2.41-16.36) & pneumonia (AHR=0.27, 95% CI = 0.11-0.68)

ConclusionsThe death rate was 10% which is close to the minimum SPHERE standard & national management protocol for SAM. Predictors for earlier hospital deaths were rural residence, IV infusion, Anemia, and Pneumonia.

category: nutrition


title: A systematic review of the effects of traditional East Asian medicine on symptom clusters during the menopausal transition

abstract:
ImportanceGiven that many midlife women use evidence-based non-pharmacologic interventions for symptom management during the menopausal transition and early postmenopause and that many women experience two or more symptoms (symptom cluster), it is important to review recent evidence on said interventions for symptom clusters. This review focuses on randomized clinical trials (RCTs) of traditional East Asian Medicine (TEAM), including acupuncture, acupressure, moxibustion, and Chinese herbal medicine, for hot flashes and one or more co-occurring symptoms experienced during peri- or post-menopause.

ObjectiveThe primary objective of the study was to review RCTs (published 2011-2021) of TEAM interventions for hot flashes and at least one other co-occurring symptom, including sleep problems, cognitive function, mood, and pain.

Evidence ReviewWe searched Medline, CINAHL Plus, and PsychINFO for RCTs reported in English from July 7, 2011, to December 31, 2021. We included RCTs that assessed women in the menopausal transition or early postmenopause with masking as appropriate; TEAM interventions were studied as the treatment with one or more comparison groups; hot flushes and at least one additional symptom from at least one of the symptom clusters were reported as an outcome (from sleep, mood, cognition, pain symptom groups). Bias was assessed.

FindingsOf 409 abstracts identified, 9 RCTs examined the effectiveness of therapies for hot flashes and at least one additional co-occurring symptom. One study reported separately on two TEAM interventions. The maximum trial duration was 6 months (range: 5 weeks - 6 months). Statistically significant improvement was reported in 2 or more symptoms: 5 of 6 studies of acupuncture, one acupressure study, one moxibustion study, 1 of 2 studies of Chinese herbal medicine.

Conclusions and RelevanceOur systematic review summarizes the recent literature on TEAM interventions for symptom clusters during the MT and EPM. A majority of studies reported symptom reduction. Overall, our findings highlight the need for further investigation with studies that include whole systems TEAM as each intervention was studied separately in the reviewed trials. Clinical practice often includes concurrent use of acupuncture, moxibustion, CHM, and advice to patients to use self-acupressure. Studying each modality separately is a scientific abstraction that does not reflect clinical practice.

Key PointsO_ST_ABSQuestion/ObjectiveC_ST_ABSWhat is the effect of traditional East Asian medicine (TEAM) therapeutics, including acupuncture, acupressure, Chinese herbal medicine, or moxibustion for hot flashes and one or more co-occurring symptoms during the menopausal transition (MT)?

FindingsNine RCTs (n=811) evaluating the effects of TEAM therapeutics on MT symptoms were included. Statistically significant improvement was reported in these studies: acupuncture (5 of 6), 1 acupressure study, 1 moxibustion study, and Chinese herbal medicine (1 of 2).

MeaningBased on the results of this systematic review, TEAM interventions demonstrate promising improvement of hot flashes and co-occurring symptoms experienced during the MT.

category: obstetrics and gynecology


title: Pilot study on the use of low molecular weight heparins in the prevention of thromboembolic disease during pregnancy and puerperium.

abstract: A pregnant woman is 4 to 5 times more likely to suffer a thromboembolic event than a non-pregnant woman. Furthermore, an increase in these episodes has been observed in women infected with SARS-CoV-2. Consequently, the prophylactic prescription of low-molecular-weight heparins (LMWH) in pregnant women is undergoing an increase that has not been evaluated yet. The aim of this study was to determine the prevalence of LMWH prescription in pregnant women at the Hospital Universitario Puerta de Hierro Majadahonda (HUPHM), according to their level of risk and its variation due to SARS-CoV-2 infection. To answer this question, a retrospective cohort of 113 women who gave birth during the month of February at the HUPHM was designed. The level of individual risk of thromboembolism, according to the Royal College guidelines (37a), was calculated with an interview to complete a questionnaire and the analysis of their clinical records. 53.6% of the women were prescribed LMWH as indicated in the guidelines. This high prevalence is explained by the high age of the pregnant women (over 35 years), the wave of the omicron variant (December 2021) and a high rate of cesarean sections (25%). On the other hand, the percentage of patients with COVID-19 was 17.6% but only 53% of them had received LMWH. In conclusion, LMWH is a very common prescription in obstetrics, mostly during puerperium, and has become even more relevant due to the COVID-19 pandemic


title: Exploring U.S. food system workers' intentions to work while ill during the early COVID-19 pandemic: a national survey analysis

abstract:
BackgroundAs "stay at home" orders were in effect, many US food workers attended in-person work during early phases of the COVID-19 pandemic, charged with maintaining normal operation of the national food supply chain. Despite establishment of a novel national paid sick leave policy, anecdotal evidence suggests that many U.S. food system workers encountered barriers to staying home when ill.

MethodsUsing quantitative and free-text analyses from a national, cross-sectional, online survey deployed from July to October 2020 among 2,535 respondents, we explored workplace and non-workplace factors associated with U.S. food system workers intentions to attend work while ill (i.e. presenteeism intentions) during the first four to six months of the COVID-19 pandemic.

ResultsOverall, 8.8% of workers surveyed reported intentions to attend work while ill. Both quantitative data and free-text responses suggest that aspects of workplace culture influenced workers decisions to attend work while ill. Workers reporting a high workplace safety climate score had half the odds of reporting presenteeism intentions (adjusted odds ratio [aOR] 0.52, 95% confidence interval (CI) 0.37, 0.75) relative to those reporting low scores. Workers described cultural barriers, including retaliation and penalties, that reduced paid sick leave access. Workers reporting low (aOR 2.06, 95% CI 1.35, 3.13) or very low (aOR 2.31, 95% CI 1.50, 3.13) levels of household food security had more than twice the odds of reporting presenteeism intentions.

ConclusionsThis study offers insights into opportunities for reducing presenteeism related to illness among food workers both during the COVID-19 pandemic and in other infectious disease scenarios. Addressing vulnerabilities like food insecurity and empowering food system workers to make health-protective decisions is important both for optimal worker health outcomes and maintaining a functioning food system.

category: occupational and environmental health


title: Cancer-associated Lactobacillus iners are genetically distinct and associated with chemoradiation resistance in cervical cancer

abstract: This study identifies a novel pathotype of cervical cancer-associated Lactobacillus iners (L. iners) that results in chemoradiation resistance in vitro and is associated with poor patient survival. Cervical cancer affects over half a million women a year around the world. Treatment for women with locally advanced cancer is delivered with definitive chemoradiation (CRT) but is curative for only 60% of patients. There are few validated molecular markers to identify patients who will respond poorly to treatment. Tumor microbiome features are associated with treatment resistance in patients with colon and pancreatic cancers, and thus we investigated their role in the response of cervical cancer to therapy. We identified a strong association between poor clinical response to CRT and tumors dominated by L. iners. Cancer-associated L. iners promoted in vitro resistance of cervical cancer cells and modified the local tumor immunologic microenvironment, while non-cancer-associated L. iners did not. Assembly of genomes from cancer-derived L. iners also demonstrated pathogenic, metabolic, and immune functions not found in healthy patients.

category: oncology


title: Prostate cancer androgen receptor activity dictates efficacy of Bipolar Androgen Therapy

abstract: Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), entitled Bipolar Androgen Therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer [1-5]. However, predictors and mechanisms of response and resistance have been ill-defined. Here we show that growth inhibition of prostate cancer models by SPA requires high androgen receptor (AR) abundance and activity and is driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pre-treatment AR activity predicts downregulation of MYC, clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance can be overcome by alternating SPA with the AR inhibitor enzalutamide, which induces adaptive upregulation of AR and re-sensitizes prostate cancer to SPA. This work identifies a predictive biomarker of response to BAT and supports a new treatment paradigm for prostate cancer involving alternating between AR inhibition and activation.


title: Computational Image Analysis Techniques, Programming Languages and Software Platforms Used in Cancer Research: A Scoping Review

abstract:
BackgroundCancer-related research, as indicated by the number of entries in Medline, the National Library of Medicine of the USA, has dominated the medical literature. An important component of this research is based on the use of computational techniques to analyse the data produced by the many acquisition modalities. This paper presents a review of the computational image analysis techniques that have been applied to cancer. The review was performed through automated mining of Medline/PubMed entries with a combination of keywords. In addition, the programming languages and software platforms through which these techniques are applied were also reviewed.

MethodsAutomatic mining of Medline/PubMed was performed with a series of specific keywords that identified different computational techniques. These keywords focused on traditional image processing and computer vision techniques, machine learning techniques, deep learning techniques, programming languages and software platforms.

ResultsThe entries related to traditional image processing and computer vision techniques have decreased at the same time that machine learning and deep learning have increased significantly. Within deep learning, the keyword that returned the highest number of entries was convolutional neural network. Within the programming languages and software environments, Fiji and ImageJ were the most popular, followed by Matlab, R, and Python. Within the more specialised softwares, QuPath has had a sharp growth overtaking other platforms like ICY and CellProfiler.

ConclusionsThe techniques of artificial intelligence techniques and deep learning have grown to overtake most other image analysis techniques and the trend at which they grow is still rising. The most used technique has been convolutional neural networks, commonly used to analyse and classify images. All the code related to this work is available through GitHub: https://github.com/youssefarafat/Scoping-Review.


title: Missense variants in the voltage sensing and pore domain of KCNH5 cause neurodevelopmental phenotypes including epilepsy

abstract:
ObjectiveKCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.

MethodsWe screened 893 individuals with developmental and epileptic encephalopathies (DEEs) for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included three previously published individuals including additional phenotypic details.

ResultsWe report a cohort of 17 patients, including nine with a recurrent de novo missense variant p.Arg327His, four with a recurrent missense variant p.Arg333His, and four additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using American College of Medical Genetics and Genomics (ACMG) criteria. All individuals presented with epilepsy with a median seizure onset at six months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalised epilepsy and normal intellect, while the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore-domain were more severely affected, with neonatal-onset DEE, profound disability, and childhood death.

ConclusionsWe report the first cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders (NDDs) and epilepsy.

category: genetic and genomic medicine


title: Factors Influencing Health Impacts among Smartphone Users in New Normal Situation: A Case Study among University Students in Thailand

abstract:
BackgroundNowadays, smartphone users are increasing across the world. Smartphones have become a necessary thing in peoples life. Using smartphones have both benefits and health effects. Therefore, this study mainly aims to develop an appropriate mobile application to be the tool for health effects and finding factors associated with a health risk from smartphone usage.

MethodsThis study was a cross-sectional descriptive study. The data was conducted in Thailand. The sample size was 500 university students. The Smartphone U Health mobile application was developed and shown in the Play Store and App Store. The self-administration was used for data collection throughout the Smart U Health. Data were entered and analyzed with licensed SPSS version 22.

ResultsThe participants, including 328 females (65.6%) and 172 males (34.4%) with an average age was 20.3{+/-}1.5 years old. The average period of using smartphones was 7.9{+/-}2.0 years. The average time spent was 8.6{+/-}3.4 hours/day. The primary physical, mental, and social health effects from smartphone usage over three months were eye pain (93.8%), feeling bored (90.4%), the participants had a communication problem with other people (84.0%), respectively. In the multivariate analysis, the significant factors associated with a health risk from smartphone usage were faculty, income, using smartphones in the classroom, experience of resting their eyes before continuing. Moreover, knowledge and practice levels were significantly associated with health risk levels from smartphone usage.

ConclusionOveruse of smartphones had many health effects. The Smart U Health mobile application might be the appropriate tool to assess smartphone users health risk levels. In the future, it may consider an intervention study to reduce health risks from smartphone usage.

category: health informatics


title: Evaluating diagnostic accuracies of Panbio™ COVID-19 rapid antigen test and RT-PCR for the detection of SARS-CoV-2 in Addis Ababa, Ethiopia using Bayesian Latent-Class Models (BLCM)

abstract:
BackgroundRapid diagnostics are vital for curving the transmission and control of COVID-19 pandemic. Although many commercially available antigen-based rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 are recommended by the WHO, their diagnostic performance has not yet been assessed in Ethiopia. So far, the vast majority of studies assessing diagnostic accuracies of rapid antigen tests considered RT-PCR as a gold standard, which inevitably leads to bias when RT-PCR is not 100% sensitive and specific. Thus, this study aimed to evaluate the diagnostic performance of Panbio  COVID-19 rapid antigen test jointly together with the RT-PCR for the detection of SARS-CoV-2.

MethodsA prospective cross-sectional study was done from July to September 2021 in Addis Ababa, Ethiopia, during the third wave of the pandemic involving two health centers and two hospitals. Diagnostic sensitivity and specificity of Panbio rapid antigen test and RT-PCR were obtained using Bayesian Latent-Class Models (BLCM).

Results438 COVID-19 presumptive clients were enrolled, 239 (54.6%) were females, of whom 196 (44.7%) had a positive RT-PCR and 158 (36.1%) were Ag-RDT positive. The Ag-RDT and RT-PCR had a sensitivity (95% CrI) of 99.6 (98.4-100), 89.3 (83.2-97.6) and specificity (95% CrI) of 93.4 (82.3 - 100), 99.1 (97.5-100) respectively. Most of the study participants, 318 (72.6) exhibited COVID-19 symptoms and the most reported was cough 191 (43.6).

ConclusionThe diagnostic performance of Panbio COVID-19 Ag RDT is coherent with the WHO established criteria of having a sensitivity [≥]80% for Ag-RDTs. Superior performance of the Panbio RDT was documented in samples with the lowest cycle-threshold RT-PCR values and clients with confirmed clinical symptoms. Thus, we recommend the use of the Panbio RDT for both symptomatic and asymptomatic individuals in clinical settings for screening purposes.


title: Identifiability of parameters in mathematical models of SARS-CoV-2 infections in humans

abstract: Determining accurate estimates for the characteristics of the severe acute respiratory syndrome coronavirus 2 in the upper and lower respiratory tracts, by fitting mathematical models to data, is made difficult by the lack of measurements early in the infection. To determine the sensitivity of viral predictions to the noise in the data, we developed a novel two-patch within-host mathematical model and investigated its ability to match population level data. We proposed several approaches that can improve practical identifiability of parameters, including an optimal experimental approach, and found that availability of viral data early in the infection is of essence for improving the accuracy of the estimates. Our findings can be useful for designing interventions.


title: Multi-omics Characterization of Neutrophil Extracellular Trap Formation in Severe and Mild COVID-19 Infections

abstract: The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics analysis of an immunologically naive SARS-CoV-2 clinical cohort from the plasma of uninfected controls, mild, and severe infections. A comparison of healthy controls and patient samples showed activation of neutrophil degranulation pathways and formation of neutrophil extracellular trap (NET) complexes that were activated in a subset of the mild infections and more prevalent in severe infections (containing multiple NET proteins in individual patient samples). As a potential mechanism to suppress NET formation, multiple redox enzymes were elevated in the mild and severe symptom population. Analysis of metabolites from the same cohort showed a 24- and 60-fold elevation in plasma L-cystine, the oxidized form of cysteine, which is a substrate of the powerful antioxidant glutathione, in mild and severe patients, respectively. Unique to patients with mild infections, the carnosine dipeptidase modifying enzyme (CNDP1) was up-regulated. The strong protein and metabolite oxidation signatures suggest multiple compensatory pathways working to suppress oxidation and NET formation in SARS-CoV-2 infections.