title: Domain expert evaluation of advanced visual computing solutions for the planning of left atrial appendage occluder interventions

abstract: Advanced visual computing solutions and 3D printing are starting to move from the engineering and development stage to being integrated into clinical pipelines for training, planning and guidance of complex interventions. Commonly, clinicians make decisions based on the exploration of patient-specific medical images in 2D flat monitors using specialised software with standard multi-planar reconstruction (MPR) visualisation. The new generation of visual computing technologies such as 3D imaging, 3D printing, 3D advanced rendering, Virtual Reality and in-silico simulations from Virtual Physiological Human models, provide complementary ways to better understand the structure and function of the organs under study and improve and personalise clinical decisions. Cardiology is a medical field where new visual computing solutions are already having an impact in decisions such as the selection of the optimal therapy for a given patient. A good example is the role of emerging visualisation technologies to choose the most appropriate settings of a left atrial appendage occluder (LAAO) device that needs to be implanted in some patients with atrial fibrillation having contraindications to drug therapies. Clinicians need to select the type and size of the LAAO device to implant, as well as the location to be deployed. Usually, interventional cardiologists make these decisions after the analysis of patient-specific medical images in 2D flat monitors with MPR visualisation, before and during the procedure, obtain manual measurements characterising the cardiac anatomy of the patient to avoid adverse events after the implantation. In this paper we evaluate several advanced visual computing solutions such as web-based 3D imaging visualisation (VIDAA platform), Virtual Reality (VRIDAA platform) and computational fluid simulations and 3D printing for the planning of LAAO device implantations. Six physicians including three interventional and three imaging cardiologists, with different level of experience in LAAO, tested the different technologies in preoperative data of 5 patients to identify the usability, friendliness, limitations and requirements for clinical translation of each technology through a qualitative questionnaire. The obtained results demonstrate the potential impact of advanced visual computing solutions to improve the planning of LAAO interventions but also a need of unification of them in order to be able to be uses in a clinical environment.


title: Patient and Provider Perceptions of a Community-Based Accompaniment Intervention for Adolescents Transitioning to Adult HIV Care in Urban Peru: A Qualitative Analysis

abstract:
IntroductionAdolescents living with HIV (ALWH) experience higher mortality rates compared to other age groups, exacerbated by suboptimal transition from pediatric to adult HIV care in which decreased adherence to antiretroviral treatment (ART) and unsuppressed viremia are frequent. Care transition--a process lasting months or years--ideally prepares ALWH for adult care and can be improved by interventions that are youth-friendly and address psychosocial issues affecting ART adherence; however, such interventions are infrequently operationalized. Community-based accompaniment (CBA), in which laypeople provide individualized support and health system navigation, can improve health outcomes among adults with HIV. Here, we describe patient and provider perceptions of a novel HIV CBA intervention called "PASEO" for ALWH in Lima, Peru.

MethodsPASEO consisted of six core elements designed to support ALWH before, during, and after transition to adult HIV care. Community-based health workers provided tailored accompaniment for ALWH aged 15-21 years over 9 months, after which adolescent participants were invited to provide feedback in a focus group or in-depth interview. HIV care personnel were also interviewed to understand their perspectives on PASEO. A semi-structured interview guide probing known acceptability constructs was used. Qualitative data were analyzed using a Framework Analysis approach and emergent themes were summarized with illustrative quotes.

ResultsWe conducted 5 focus groups and 11 in-depth interviews among N=26 ALWH and 9 key-informant interviews with HIV care personnel. ALWH participants included those with both vertically- and behaviorally acquired HIV. ALWH praised PASEO, attributing increased ART adherence to the project. Improved mental health, independence, self-acceptance, and knowledge on how to manage their HIV were frequently cited. HIV professionals similarly voiced strong support of PASEO. Both ALWH and HIV professionals expressed hope that PASEO would be scaled. HIV professionals voiced concerns regarding financing PASEO in the future.

ConclusionA multicomponent CBA intervention to increase ART adherence among ALWH in Peru was highly acceptable by ALWH and HIV program personnel. Future research should determine the efficacy and economic impact of the intervention.

category: hiv aids


title: qPCR in a suitcase for rapid Plasmodium falciparum and Plasmodium vivax surveillance in Ethiopia

abstract: Many Plasmodium spp. infections, both in clinical and asymptomatic patients, are below the limit of detection of light microscopy or rapid diagnostic test (RDT). Molecular diagnosis by qPCR can be valuable for surveillance, but is often hampered by absence of laboratory capacity in endemic countries. To overcome this limitation, we optimized and tested a mobile qPCR laboratory for molecular diagnosis in Ziway, Ethiopia, where transmission intensity is low. Protocols were optimized to achieve high throughput and minimize costs and weight for easy transport. 899 samples from febrile patients and 1021 samples from asymptomatic individuals were screened by local microscopy, RDT, and qPCR within a period of six weeks. 34/52 clinical Plasmodium falciparum infections were missed by microscopy and RDT. Only 4 asymptomatic infections were detected. No hrp2 deletions were observed among 25 samples typed, but 19/24 samples carried hrp3 deletions. The majority (25/41) of Plasmodium vivax infections (1371 samples screened) were found among asymptomatic individuals. All asymptomatic P. vivax infections were negative by microscopy and RDT. In conclusion, the mobile laboratory described here can identify hidden parasite reservoirs within a short period of time, and thus inform malaria control activities.

category: infectious diseases


title: Disease profile and plasma neutralizing activity of post-vaccination Omicron BA.1 infection in Tianjin, China: a retrospective study

abstract:
BackgroundSARS-CoV-2 Omicron variant BA.1 first emerged on the Chinese mainland in January 2022 in Tianjin and caused a large wave of infections. During mass PCR testing, a total of 430 cases infected with Omicron were recorded between January 8 and February 7, 2022, with no new infections detected for the following 16 days. Most patients had been vaccinated with SARS-CoV-2 inactivated vaccines. The disease profile associated with BA.1 infection, especially after vaccination with inactivated vaccines, is unclear. Whether BA.1 breakthrough infection after receiving inactivated vaccine could create a strong enough humoral immunity barrier against Omicron is not yet investigated.

MethodsWe collected the clinical information and vaccination history of the 430 COVID-19 patients infected with Omicron BA.1. Re-positive cases and inflammation markers were monitored during the patients convalescence phase. Ordered multiclass logistic regression model was used to identify risk factors for COVID-19 disease severity. Authentic virus neutralization assays against SARS-CoV-2 wildtype, Beta and Omicron BA.1 were conducted to examine the plasma neutralizing titers induced after post-vaccination Omicron BA.1 infection, and were compared to a group of uninfected healthy individuals who were selected to have a matched vaccination profile.

FindingsAmong the 430 patients, 316 (73.5%) were adults with a median age of 47 years, and 114 (26.5%) were under-age with a median age of 10 years. Female and male patients account for 55.6% and 44.4%, respectively. Most of the patients presented with mild (47.7%) to moderate diseases (50.2%), with only 2 severe cases (0.5%) and 7 (1.6%) asymptomatic infections. No death was recorded. 341 (79.3%) of the 430 patients received inactivated vaccines (54.3% BBIBP-CorV vs. 45.5% CoronaVac), 49 (11.4%) received adenovirus-vectored vaccines (Ad5-nCoV), 2 (0.5%) received recombinant protein subunit vaccines (ZF2001), and 38 (8.8%) received no vaccination. No vaccination is associated with a substantially higher ICU admission rate among Omicron BA.1 infected patients (2.0% for vaccinated patients vs. 23.7% for unvaccinated patients, P<0.001). Compared with adults, child patients presented with less severe illness (82.5% mild cases for children vs. 35.1% for adults, P<0.001), no ICU admission, fewer comorbidities (3.5% vs. 53.2%, P<0.001), and less chance of turning re-positive on nucleic acid tests (12.3% vs. 22.5%, P=0.019). For adult patients, compared with no prior vaccination, receiving 3 doses of inactivated vaccine was associated with significantly lower risk of severe disease (OR 0.227 [0.065-0.787], P=0.020), less ICU admission (OR 0.023 [0.002-0.214], P=0.001), lower re-positive rate on PCR (OR 0.240 [0.098-0.587], P=0.002), and shorter duration of hospitalization and recovery (OR 0.233 [0.091-0.596], P=0.002). At the beginning of the convalescence phase, patients who had received 3 doses of inactivated vaccine had substantially lower systemic immune-inflammation index (SII) and C-reactive protein than unvaccinated patients, while CD4+/CD8+ ratio, activated Treg cells and Th1/Th2 ratio were higher compared to their 2-dose counterparts, suggesting that receipt of 3 doses of inactivated vaccine could step up inflammation resolution after infection. Plasma neutralization titers against Omicron, Beta, and wildtype significantly increased after breakthrough infection with Omicron. Moderate symptoms were associated with higher plasma neutralization titers than mild symptoms. However, vaccination profiles prior to infection, whether 2 doses versus 3 doses or types of vaccines, had no significant effect on post-infection neutralization titer. Among recipients of 3 doses of CoronaVac, infection with Omicron BA.1 largely increased neutralization titers against Omicron BA.1 (8.7x), Beta (4.5x), and wildtype (2.2x), compared with uninfected healthy individuals who have a matched vaccination profile.

InterpretationReceipt of 3-dose inactivated vaccines can substantially reduce the disease severity of Omicron BA.1 infection, with most vaccinated patients presenting with mild to moderate illness. Child patients present with less severe disease than adult patients after infection. Omicron BA.1 convalescents who had received inactivated vaccines showed significantly increased plasma neutralizing antibody titers against Omicron BA.1, Beta, and wildtype SARS-CoV-2 compared with vaccinated healthy individuals.

FundingThis research is supported by Changping Laboratory (CPL-1233) and the Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), sponsored by the Ministry of Science and Technology of the Peoples Republic of China.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevious studies (many of which have not been peer-reviewed) have reported inconsistent findings regarding the effect of inactivated vaccines against the Omicron variant. On Mar 6, 2022, we searched PubMed with the query "(SARS-CoV-2) AND ((Neutralisation) OR (Neutralisation)) AND ((Omicron) OR (BA.1)) AND (inactivated vaccine)", without date or language restrictions. This search identified 18 articles, of which 13 were directly relevant.

Notably, the participants in many of these studies have received only one or two doses of inactivated vaccine with heterologous booster vaccination; other studies have a limited number of participants receiving inactivated vaccines.

Added value of this studyTo date, this is the first study to report on the protective effect of inactivated vaccines against the severe disease caused by the Omicron variant. We examine and compare the disease profile of adults and children. Furthermore, we estimate the effect of post-vaccination omicron infection on plasma neutralization titers against Omicron and other SARS-COV-2 variants. Specifically, the disease profile of Omicron convalescents who had received two-dose primary series of inactivated vaccines with or without a booster dose prior to infection is compared with unvaccinated patients. We also analyzed the effect of infection on neutralizing activity by comparing vaccinated convalescents with vaccinated healthy individuals with matched vaccination profiles.

Implications of all the available evidenceCompared with adults, child patients infected with Omicron tend to present with less severe disease and are less likely to turn re-positive on nucleic acid tests. Receipt of two-dose primary series or three doses of inactivated vaccine is a protective factor against severe disease, ICU admission, re-positive PCR and longer hospitalization. The protection afforded by a booster dose is stronger than two-dose primary series alone. Besides vaccination, infection with Omicron is also a key factor for elevated neutralizing antibody titers, enabling cross-neutralization against Omicron, wildtype (WT) and the Beta variant.


title: SARS-CoV-2 spike 340 and 337 mutations in Omicron variants are selected after Sotrovimab infusion in immunocompromised patients

abstract:
After monoclonal antibody sotrovimab implementation, Rockett et al have warned on March 9th about two resistant mutations in the spike at position 337 and 340 occurring within the first week in four immunocompromised patients infected by a Delta variant and resulting in viable infection up to 25 days. As sotrovimab is currently the only effective treatment against BA.1 lineage of Omicron variant, we investigated the presence of these mutations in our 22,908 Omicron sequences performed from December 2021 to March 2022.

Among 25 Omicron sequences with S:337 and S:340 substitutions, 9 were reported in six patients who had available clinical data and a follow up. All were immunicompromised, and presented a rapid selection of these mutations after sotrovimab monotherapy infusion.

With these findings, we underscore that although these mutations are rare, they have been exclusively reported in immunocompromised patients treated with sotrovimab. We urge to consider monoclonal antibody as monotherapy in immunocompromised patients as a risk for escape mutants selection.


title: Heterologous Gam-COVID-Vac (Sputnik V) / mRNA-1273 (Moderna) vaccination induces a stronger humoral response than homologous Sputnik V in a real-world data analysis

abstract:
IntroductionGrowing data are demonstrating safety and immunogenicity of heterologous vaccination schemes against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. This strategy opens up the possibility of a shorter path towards the end of the pandemic.

ObjectiveTo compare the homologous prime-boost vaccination scheme of Gam-COVID-Vac (Sputnik V, SpV) to its heterologous combination with mRNA-1273 (Moderna, Mod) vaccine.

MethodsSARS-CoV-2 anti-spike (S)-receptor binding domain (RBD) IgG concentration was assessed three to seven weeks after complete vaccination. Reactogenicity was evaluated by declared side events and medical assistance required until day 7 post-boost.

ResultsOf 190 participants enrolled, 105 received homologous SpV/SpV and the remaining heterologous SpV/Mod vaccination scheme, respectively. Median (interquartile range, IQR) age was 54 (37-63) years, 132 (69.5%) were female and 46 (24.2%) individuals had a prior confirmed COVID-19. Anti-S-RBD IgG median (IQR) titers were significantly higher for SpV/Mod [2511 (1476-3992) BAU/mL] than for SpV/SpV [582 (209-1609) BAU/mL, p<0.001] vaccination scheme. In a linear model adjusted for age, gender, time to the serological assay and time between doses, SpV/Mod [4.154 (6.585-615.554), p<0.001] and prior COVID [3.732 (8.641-202.010), p<0.001] were independently associated with higher anti-S-RBD IgG values. A higher frequency of mild-moderate adverse effects was associated with the heterologous scheme, although it was well tolerated by all individuals and no medical assistance was required.

ConclusionThe heterologous SpV/Mod combination against SARS-CoV-2 is well tolerated and significantly increases humoral immune response as compared to the homologous SpV/SpV immunization.


title: Monitoring real-time transmission heterogeneity from Incidence data

abstract:
The transmission heterogeneity of an epidemic is associated with a complex mixture of host, pathogen and environmental factors. And it may indicate superspreading events to reduce the efficiency of population-level control measures and to sustain the epidemic over a larger scale and a longer duration. Methods have been proposed to identify significant transmission heterogeneity in historic epidemics based on several data sources, such as contact history, viral genomes and spatial information, which is sophisticated and may not be available, and more importantly ignore the temporal trend of transmission heterogeneity. Here we attempted to establish a convenient method to estimate real-time heterogeneity over an epidemic. Within the branching process framework, we introduced an instant-individualheterogenous infectiousness model to jointly characterized the variation in infectiousness both between individuals and among different times. With this model, we could simultaneously estimate the transmission heterogeneity and the reproduction number from incidence time series. We validated the model with both simulated data and five historic epidemics. Our estimates of the overall and real-time heterogeneities of the five epidemics were consistent with those presented in the literature. Additionally, our model is robust to the ubiquitous bias of under-reporting and misspecification of serial interval. By analyzing the recent data from South Africa, we found evidences that the Omicron might be of more significant transmission heterogeneity than the Delta. Our model based on incidence data was proved to be reliable in estimating the real-time transmission heterogeneity.

Author summaryThe transmission of many infectious diseases is usually heterogeneous in time and space. Such transmission heterogeneity may indicate superspreading events (where some infected individuals transmit to disproportionately more susceptible than others), reduce the efficiency of the population-level control measures, and sustain the epidemic over a larger scale and a longer duration. Classical methods of monitoring epidemic spread centered on the reproduction number which represent the average transmission potential of the epidemic at the population level, but failed to reflect the systematic variation in transmission. Several recent methods have been proposed to identify significant transmission heterogeneity in the epidemics such as Ebola, MERS, COVID-19. However, these methods are developed based on some sophisticated information such as contact history, viral genome and spatial information, of the confirmed cases, which are typically field-specific and not easy to generalize. In this study, we proposed a simple and generic method of estimating transmission heterogeneity from incidence time series, which provided consistent estimation of heterogeneity with those records with sophisticated data. It also helps in exploring the transmission heterogeneity of the newly emerging variant of Omicron. Our model enhances current understanding of epidemic dynamics, and highlight the potential importance of targeted control measures.


title: Prevalence and risk factors of Schistosomiasis among school aged children in Al- Fashir, North Darfur state, Sudan: a cross sectional study

abstract:
ObjectiveSchistosomiasis represents a significant health problem in Sudan. School aged children who live in areas with poor sanitation are often at risk because they tend to spend time swimming or bathing in water containing infectious cercariae. Therefore, this study aimed to investigate schistosomiasis in terms of prevalence of the infection, and its risk factors among school aged children at Al- Fashir, the capital city of North Darfur state in Sudan.

ResultsIn this study, S. haematobium was detected in 6.1% of the school age children at Al- Fashir. Also, hematuria was detected in 85.7% of infected patients, and there was significant correlation between hematuria and presence of S. haematobium eggs (P. value= 0.001). Regarding the risk factor, the low prevalence rate of S. haematobium was observed in populations who depend on faucets as water sources and live in Nifasha and Zamzam camps.


title: Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: a secondary analysis of the CAPTAIN prospective multicenter cohort study.

abstract:
BackgroundAlthough sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates.

MethodsA secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters.

ResultsTwo hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers.

ConclusionsIn this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies.

Trial registrationThe CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

category: intensive care and critical care medicine


title: Toward Evaluation of Disseminated Effects of Medications for Opioid Use Disorder within Provider-Based Clusters Using Routinely-Collected Health Data

abstract: Routinely-collected health data can be employed to emulate a target trial when randomized trial data are not available. Patients within provider-based clusters likely exert and share influence on each others treatment preferences and subsequent health outcomes and this is known as dissemination or spillover. Extending a framework to replicate an idealized two-stage randomized trial using routinely-collected health data, an evaluation of disseminated effects within provider-based clusters is possible. In this paper, we propose a novel application of causal inference methods for dissemination to retrospective cohort studies in administrative claims data and evaluate the impact of the normality of the random effects distribution for the cluster-level propensity score on estimation of the causal parameters. An extensive simulation study was conducted to study the robustness of the methods under different distributions of the random effects. We applied these methods to evaluate baseline prescription for medications for opioid use disorder among a cohort of patients diagnosed opioid use disorder and adjust for baseline confounders using information obtained from an administrative claims database. We discuss future research directions in this setting to better address unmeasured confounding in the presence of disseminated effects.

category: addiction medicine


title: Comparing the efficacy and safety of direct oral anticoagulants versus Vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis

abstract:
BackgroundThromboprophylaxis is the cornerstone strategy for thrombotic antiphospholipid syndrome (APS). Data comparing direct oral anticoagulants (DOACs) to Vitamin K antagonists (VKAs) in the secondary prevention of thrombosis in APS patients remain contentious.

ObjectivesWe aim to review and analyze literature on the efficacy and safety of DOACs compared to VKAs in treating patients with APS. A literature search was performed from inception to March 1, 2022. Subgroups were analyzed based on the risk stratification of APS profiles and different DOAC types.

ResultsA total of 9 studies with 1131 patients were included in the meta-analysis. High-risk APS patients (triple positive APS) who used DOACs displayed an increased risk of recurrent thrombosis (RR=3.65, 95% CI:1.49-8.93; I2=29%, P=0.005) compared to those taking VKAs. Similar risk of recurrent thrombosis or major bleeding was noted in low-risk APS patients (single or double antibody-positive) upon administering DOACs or VKAs. The utilization of Rivaroxaban was associated with a high risk of recurrent thromboses (RR=2.63; 95% CI, 1.56-4.42; I2 =0, P=0.0003), particularly recurrent arterial thromboses (RR=4.52; 95% CI, 1.99-10.29; I2 =0, P=0.18) in overall APS patients. Comparisons of the rate of recurrent thrombosis events and major bleeding events when using dabigatran or apixaban versus VKAs yielded no statistical differences.

ConclusionsIn the absence of contraindications, this meta-analysis suggests that VKAs remain the first-choice treatment for high-risk APS patients, with DOACs a more appropriate option for low-risk APS patients. Different DOACs may exhibit different levels of efficacy and safety for thromboprophylaxis in APS patients and require further exploration.

category: cardiovascular medicine


title: Clinical validation of digital biomarkers and machine learning models for remote measurement of psoriasis and psoriatic arthritis

abstract:
BackgroundPsoriasis and psoriatic arthritis are common immune-mediated inflammatory conditions that primarily affect the skin, joints and entheses and can lead to significant disability and worsening quality of life. Although early recognition and treatment can prevent the development of permanent damage, psoriatic disease remains underdiagnosed and undertreated due in part to the disparity between disease prevalence and relative lack of access to clinical specialists in dermatology and rheumatology. Remote patient self-assessment aided by smartphone sensor technology may be able to address these gaps in care, however, these innovative disease measurements require robust clinical validation.

MethodsWe developed smartphone-based assessments, collectively named the Psorcast suite, that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. The image and motion sensor data collected by these assessments was processed to generate digital biomarkers or machine learning models to detect psoriatic disease phenotypes. To evaluate these digital endpoints, a cross-sectional, in-clinic validation study was performed with 92 participants across two specialized academic sites consisting of healthy controls and participants diagnosed with psoriasis and/or psoriatic arthritis.

FindingsIn the domain of skin disease, digital patient assessment of percent body surface area (BSA) affected with psoriasis demonstrated very strong concordance (CCC = 0{middle dot}94, [95%CI = 0{middle dot}91-0{middle dot}96]) with physician-assessed BSA. Patient-captured psoriatic plaque photos were remotely assessed by physicians and compared to in-clinic Physician Global Assessment parameters for the same plaque with fair to moderate concordance (CCCerythema=0{middle dot}72 [0{middle dot}59-0{middle dot}85]; CCCinduration=0{middle dot}72 [0{middle dot}62-0{middle dot}82]; CCCscaling=0{middle dot}60 [0{middle dot}48-0{middle dot}72]). Arm range of motion was measured by the Digital Jar Open assessment to classify physician-assessed upper extremity involvement with joint tenderness or enthesitis, demonstrating an AUROC = 0{middle dot}68 (0{middle dot}47-0{middle dot}85). Patient-captured hand photos were processed with object detection and deep learning models to classify clinically-diagnosed nail psoriasis with an accuracy of 0{middle dot}76, which is on par with remote physician rating of nail images (avg. accuracy = 0{middle dot}63) with model performance maintaining accuracy when raters were too unsure or image quality was too poor for a remote assessment.

InterpretationThe Psorcast digital assessments, performed by patient self-measurement, achieve significant clinical validity when compared to in-person physical exams. These assessments should be considered appropriately validated for self-monitoring and exploratory research applications, particularly those that require frequent, remote disease measurements. However, further validation in larger cohorts will be necessary to demonstrate robustness and generalizability across populations for use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and available to the scientific community.

FundingThis work is funded by the Psorcast Digital Biomarker Consortium consisting of Sage Bionetworks, Psoriasis and Psoriatic Arthritis Centers for Multicenter Advancement Network (PPACMAN), Novartis, UCB, Pfizer, and Janssen Pharmaceuticals. J.U.S work was supported by the Snyder Family Foundation and the Riley Family Foundation.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSNo systematic literature review was performed. Patient self-measurement with smartphone sensors has been shown to be clinically valid for assessing signs and symptoms such as tremor, gait, physical activity, or range of motion across multiple disease indications. While smartphone-based applications have been developed for digitally tracking psoriatic disease, they have largely focused on questionnaire-based patient reported outcomes.

Added value of this studyTo our knowledge, Psorcast is the first application using ubiquitous smartphone sensor technology for patients to remotely measure their psoriatic disease phenotypes, including detection of nail psoriasis and a continuous variable outcome measure of joint tenderness and enthesitis based on range of motion. This study not only developed a suite of novel, smartphone sensor-based assessment that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms, but provides clinical validation of these measures.

Implications of all the available evidenceThe developed Psorcast suite of measurements can serve as groundwork for patient-driven, remote measurement of psoriatic disease. The use and continued development of this technology opens up new possibilities for both clinical care and research endeavors on a large scale. Psorcast measurements are currently being validated for their ability to assess disease changes longitudinally, allowing for more frequent symptom monitoring in clinical trials, more granular insight into the time course of medication action, and possible identification of responders from non-responders to specific therapies.

category: dermatology


title: Association between metabolic syndrome and humoral immune response to Pfizer BioNTech vaccine in healthcare workers

abstract:
PurposeThe clustering of metabolic abnormalities may weaken vaccine-induced immunity, but epidemiological data regarding SARS-CoV-2 vaccines are scarce. The present study examined the cross-sectional association between metabolic syndrome (MetS) and humoral immune response to Pfizer-BioNTech vaccine among healthcare workers.

MethodsParticipants were 946 healthcare workers, aged 21-75 years, who had completed the second dose of Pfizer-BioNTech vaccine 1-3 months before the survey. MetS was defined according to the Joint Interim Statement. SARS-CoV-2 spike immunoglobulin G (IgG) antibody was measured using quantitative assays. Multivariable linear regression was used to estimate the geometric mean titers (GMT) and geometric mean ratio (GMR) of IgG titers, relative to MetS status.

ResultsA total of 51 participants (5.4%) had MetS. Healthcare workers with MetS had a significantly lower IgG titer (GMT 3882; 95% confidence interval [CI], 3124-4824) than those without MetS (GMT 5033; 95% CI, 4395-5764); the GMR was 0.77 (95% CI 0.64-0.93). The GMR for IgG titers among those having 0 (reference group), 1, 2, 3, or [≥] 4 MetS components was 1.00, 1.00, 0.89, 0.86 and 0.61, respectively (Ptrend = 0.004).

ConclusionResults suggest that having MetS and a greater number of its components are associated with a weaker humoral immune response to the Pfizer-BioNTech vaccine.

category: endocrinology


title: Malaria and typhoid fever coinfection among patients presenting with febrile illnesses in Ga West Municipality, Ghana

abstract:
BackgroundMalaria and typhoid fever coinfection presents major public health problems especially in the tropics and sub-tropics where malaria and typhoid fever are co-endemic. Clinicians often treat both infections concurrently without laboratory confirmation. However, concurrent treatment has public health implications as irrational use of antibiotics or anti-malarials may lead to the emergence of drug resistance, unnecessary cost and exposure of patients to unnecessary side effects. This study determined the proportion of febrile conditions attributable to either malaria and/or typhoid fever and the susceptibility patterns of Salmonella spp. isolates to commonly used antimicrobial agents in Ghana.

MethodsOne hundred and fifty-seven (157) febrile patients attending the Ga West Municipal Hospital, Ghana, from February to May 2017 were sampled. Blood samples were collected for cultivation of pathogenic bacteria and the susceptibility of the Salmonella isolates to antimicrobial agents was performed using the Kirby-Bauer disk diffusion method with antibiotic discs on Muller Hinton agar plates. For each sample, conventional Widal tests for the detection of Salmonella spp were done as well as blood film preparation for detection of Plasmodium spp. Data on the socio-demographic and clinical characteristics of the study participants were collected using an android technology software kobo-collect by interview. Data were analyzed using Stata version 13 statistical Software. Logistic regression models were run to determine odds ratio (OR) and the direction of association between dependent and independent variables, setting p-value at <0.05 for statistical significance.

ResultsOf the total number of patients aged 2-37 years (median age = 6 years, IQR 3-11), 82 (52.2%) were females. The proportion of febrile patients with falciparum malaria were 57/157 (36.3%), while Salmonella typhi O and H antigens were detected in 23/157 (14.6%) of the samples. The detection rate of Salmonella spp in febrile patients was 10/157 (6.4%). Malaria and typhoid fever coinfection using Widal test and blood culture was 9 (5.7%) and 3 (1.9%), respectively. The isolates were highly susceptible to cefotaxime, ceftriaxone, ciprofloxacin, and amikacin but resistant to ampicillin, tetracycline, co-trimoxazole, gentamicin, cefuroxime, chloramphenicol, and meropenem.

ConclusionPlasmodium falciparum and Salmonella spp coinfections were only up to 1.9%, while malaria and typhoid fever, individually, were responsible for 36.3% and 6.4%, respectively. Treatment of febrile conditions must be based on laboratory findings in order not to expose patients to unnecessary side effects of antibiotics and reduce the emergence and spread of drug resistance against antibiotics.

category: epidemiology


title: A meta-epidemiological assessment of transparency indicators of infectious disease models

abstract: Mathematical models have become very influential, especially during the COVID-19 pandemic. Data and code sharing are indispensable for reproducing them, protocol registration may be useful sometimes, and declarations of conflicts of interest (COIs) and of funding are quintessential for transparency. Here, we evaluated these features in publications of infectious disease-related models and assessed whether there were differences before and during the COVID-19 pandemic and for COVID-19 models versus models for other diseases. We analysed all PubMed Central open access publications of infectious disease models published in 2019 and 2021 using previously validated text mining algorithms of transparency indicators. We evaluated 1338 articles: 216 from 2019 and 1122 from 2021 (of which 818 were on COVID-19); almost a six-fold increase in publications within the field. 511 (39.2%) were compartmental models, 337 (25.2%) were time series, 279 (20.9%) were spatiotemporal, 186 (13.9%) were agent-based and 25 (1.9%) contained multiple model types. 288 (21.5%) articles shared code, 332 (24.8%) shared data, 6 (0.4%) were registered, and 1197 (89.5%) and 1109 (82.9%) contained COI and funding statements, respectively. There was no major changes in transparency indicators between 2019 and 2021. COVID-19 articles were less likely to have funding statements and more likely to share code. Manual assessment of 10% of the articles that were identified by the text mining algorithms as fulfilling transparency indicators showed that 24/29 (82.8%) actually shared code, 29/33 (87.9%) actually shared data; and all had COI and funding statements, but 95.8% disclosed no conflict and 11.7% reported no funding. On manual assessment, 5/6 articles identified as registered had indeed been registered. Transparency in infectious disease modelling is relatively low, especially for data and code sharing. This is concerning, considering the nature of this research and the heightened influence it has acquired.


title: Longitudinal change in cognition in older adults in Uganda: a prospective population study

abstract:
IntroductionDementia is an important and growing issue in sub-Saharan Africa, but epidemiological data are lacking. Risk factors may differ from other regions due to high stroke incidence and HIV prevalence. Understanding the epidemiology of cognition in older adults in Africa is crucial for informing public health strategies to improve the lives of people with dementia and their carers.

MethodsThe Wellbeing of Older People Study in Uganda is an open cohort of adults aged 50+ with and without HIV, established in 2009. Detailed socio-demographic and health data have been collected at four waves spanning 10 years, including cognitive assessment using internationally validated WHO-recommended tests: verbal recall, digit span, and verbal fluency. Mortality data was collected until the end of the fourth wave (2019). We examined associations of low baseline cognition scores and cognitive decline over time, care needs of people with lower cognition, and the relationship between cognition and mortality.

ResultsData were collected on 811 participants. Older age, lower educational attainment, lower socio-economic position, and extremes of BMI were associated with lower cognition scores. Cognition declined faster at older ages, but rate of decline was not associated with cardiovascular disease or HIV. People with lower cognition required more assistance with Activities of Daily Living, but mortality rates were similar across the range of cognition.

ConclusionsThe crucial next step will be investigating the determinants of low cognition scores and clinical dementia, to better understand the clinical relevance of these findings to inform public health planning in sub-Saharan Africa.


title: Understanding and comparing the globe-trotting cancer patient with the locally managed patient: A case control study

abstract:
Medical tourism is characterized by people seeking treatment abroad for various medical conditions due to varied reasons, many of whom benefit from specialized care for non-communicable diseases. Conversely, there are associated negative effects such as medical complications and weakened health systems. Currently, there is paucity of scientific evidence on factors influencing seeking treatment benefits abroad. This study sought to compare patient-related factors associated with choice of cancer treatment center locally or abroad, to understand reasons for seeking treatment outside Kenya.

Materials and MethodsAs a case-control study, 254 cancer patients were randomly sampled to compare responses from those who chose to receive treatment abroad or in Kenya. The cases were recruited from Ministry of Health while the controls from Kenyatta National Hospital and Texas Cancer Center. Data was analyzed using SPSS Software Version 21. Descriptive statistics, bivariate and multiple logistic regression analysis was carried out. Level of significance was set at 5%.

ResultsOut of 254 respondents, 174 (69.5%) were treated for cancer in Kenya and 80 (31.5%) in India. We found that cost effectiveness was a significant factor for over 73% of all respondents. The study revealed independent predictors for seeking treatment in India were: monthly income higher than US$ 250; every additional month from diagnosis increased likelihood by 1.16 times; physician advice (Odds Ratio(OR) 66; 95% Confidence Interval(CI) 7.9 -552.9); friends and family (OR 42; 95% CI 7.07-248.6); and perception of better quality of care (OR 22.5; 95% CI 2.2-230.6).

ConclusionReasons patients with cancer sought treatment in India are multifactorial. Several of these can be addressed to reverse out-ward bound medical tourism and position Kenya to be a regional hub as per the countrys development blueprint. It will require strengthening the health system accordingly and sensitizing the medical fraternity and general public on the same.


title: Microbiological risk ranking of foodborne pathogens and food products in scarce-data settings.

abstract: In the absence of epidemiological, microbiological or outbreak data, systematic identification of the hazards and food products posing the higher risk to the consumers is challenging. It is usually in Low- and Middle-Income Countries (LMICs), where the burden of foodborne disease is highest that data tend to be particularly scarce. In this study, we propose qualitative risk-ranking methods for pathogens and food products that can be used in settings where scarcity of data on the frequency/concentration of pathogens in foodstuff is a barrier towards the use of classical risk assessment frameworks. The approach integrates the existing knowledge on foodborne pathogens, manufacturing processes and intrinsic/extrinsic properties of food products with key context-specific information regarding the supply chain(s), characteristics of the Food Business Operators (FBOs) and cultural habits to identify: (i) the pathogens that should be considered as a "High" food safety priority and (ii) the food products posing the higher risk of consumer exposure to microbiological hazards via oral (ingestion) route. When applied to the dairy sector of Andhra Pradesh (India) as a case study, E. coli O157:H7, Salmonella spp., S. aureus and L. monocytogenes were identified as a "High" food safety priority across all FBOs, C. sakazakii a "High" priority for the FBOs producing infant formula/milk powder whilst Shigella spp. and Cryptosporidium spp. a "High" priority when considering the FBOs operating towards the informal end of the formal-informal spectrum. The risk ranking of dairy products was informed by a preliminary cluster analysis for early identification of products that are similar with regards to intrinsic/extrinsic features known to drive the microbiological risk. Products manufactured/retailed by FBOs in the informal market were considered as posing a "High" risk for the consumers due to a widespread lack of compliance to sanitary regulations. For dairy products produced by FBOs operating in the middle and formal end of the formal-informal spectrum, the risk of consumers exposure to microbiological hazards ranged from "Medium" to "Extremely low" depending on the FBO and the intrinsic/extrinsic properties of the products. While providing risk estimates of lower resolution if compared to data-driven risk assessments, the proposed method maximises the value of the information that can be easily gathered in LMICs and provide informative outputs to support food safety decision-making in contexts where resources to be allocated for prevention of foodborne diseases are limited and the food system is complex.


title: Effectiveness of COVID-19 mRNA vaccine booster dose relative to primary series during a period of Omicron circulation

abstract: During a period of Omicron variant circulation, we estimated relative VE of COVID-19 mRNA booster vaccination versus primary two-dose series in an ongoing community cohort. Relative VE was 66% (95% CI: 46%, 79%) favoring the booster dose compared to primary series vaccination. Our results support current booster recommendations.


title: Dose-response modelling of endemic coronavirus and SARS-CoV-2: human challenge trials reveal the individual variation in susceptibility

abstract:
We propose a mathematical framework to analyze and interpret the outcomes of human challenge trials. We present plausible infection risks with HCoV-229E and SARS-CoV-2 over a wide range of infectious dose, and suggest ways to improve the design of future trials and to translate its outcomes to the general population.

One sentence summaryWe rephrase dose-response models in terms of heterogeneity in susceptibility in order to present the possible range of infection risks for endemic coronaviruses and SARS-CoV-2


title: Effectiveness of a psychosocial training intervention in reducing psychological distress among caregivers of intellectually disabled children in Malawi - a randomized wait-list trial

abstract:
BackgroundRates of disability are high in resource-poor settings with eighty-five percent of disabled children living in these settings. Long-term caregiving for disabled children is associated with fatigue, financial difficulties, parenting distress, and other psychological issues. Studies have shown a link between parenting children with intellectual disabilities and psychological distress as well as overall Health-Related Quality of Life (QoL). However, with interventions, these negative impacts may not be as severe as thought before. This study aimed at developing and testing the impact of a contextualized psychological intervention, Titukulane, in reducing psychological distress among caregivers with intellectually disabled children in Malawi.

MethodsWe conducted a randomized waitlist trial of a psychosocial training intervention (Titukulane) provided to caregivers of children with intellectual disabilities. Caregivers of children with intellectual disabilities aged 0 to 18 years were recruited, screened, and then enrolled in the trial through two disability organizations operating in Mzuzu (St John of God) and Lilongwe (Children of Blessings). They were then randomized in blocks to the Titukulane intervention or waitlist and provided with the intervention or standard care for 3 months respectively. Assessment of socioeconomic status, age, gender, and maternal psychological distress (through the Self Reported Questionnaire (SRQ) were conducted at baseline and follow-up.

ResultsWe found that psychological distress on SRQ was significantly lower in caregivers of children with intellectual disability in the Titukulane intervention in comparison to the waitlist control group even when the confounding variables of age, gender, and social-economical status were taken into account (Cohen d = 0.08; CI = 0.33-0.754; p =0.0005).

ConclusionsPyschosocial interventions such as the Titukulane intervention provided over a few months can improve caregiver mental health and quality of life - an important factor for supporting families of children with intellectual disability.

category: psychiatry and clinical psychology


title: Growing up unloved: the enduring consequence of childhood emotional neglect on the qualia of memory and imagination.

abstract: Childhood Adversity (CA) is one of the strongest factors associated with the onset of Major Depressive Disorder (MDD), and both CA and MDD have been linked to altered hippocampal structure/function. The current study aimed to explore the relationships between retrospectively reported childhood emotional neglect (CEN), current wellbeing and depressive symptoms, and a range of hippocampal-dependent cognitive functions i.e., anterograde learning and memory, episodic memory recollection, and imagination (episodic future thinking and scene construction). In two-wave recruitment periods at undergraduate intake 2014-15 (Cohort 1) and 2016-17 (Cohort 2), a combined cohort of n=1485 university students completed online surveys, with n=64 further participating in experimental testing session. As anticipated, higher CEN ratings consistently correlated with poorer current wellbeing and higher depressive symptoms. However, whilst the anticipated relationships between CEN, current wellbeing, and subjectively reported estimates of hippocampal-dependent cognitions were observed in the data reported in the online survey, an unexpectedly circumscribed pattern was observed on formal in-person examination of these cognitive functions. More specifically, higher CEN related to less vivid and less detailed imagined future/scene constructions and with an attenuated sense of presence and emotional valence during these simulations. A similar pattern was not evidence when participants simulated experienced past events (i.e. episodic memories). Current depression scores did not consistently correlate with vividness, detail, or emotional valence. In addition, and contrary to expectation, no relationship between CEN, depressive symptoms, and the spatial coherence of imagined or recollected events was seen. Moreover, neither CEN nor depressive symptoms correlated with many key measures of anterograde memory. Hence, we observed a highly specific constellation of impairment related to CEN when explored on a simulation per simulation basis, that was not obviously linked to altered hippocampal function, indicating that the relationship between CEN, hippocampal function, and subsequent psychopathology may not readily explained by either spatial or mnemonic hippocampal- related deficits. We consider whether the observed experiential differences in the qualia of imagined simulations may represent an important therapeutic target to decrease a CEN-driven latent vulnerability to MDD.


title: To mask, or not to mask, Alice and Bob's dating dilemma

abstract: AO_SCPLOWBSTRACTC_SCPLOWFace masking in current COVID-19 pandemic seems to be a deceivingly simple decision-making problem due to its multifaceted nature. Questions arising from masking span biomedicine, epidemiology, physics, and human behaviors. While science has shown masks work generally, human behaviors (particularly under influences of politics) complicate the problem significantly given science generally assumes rationality and our minds are not always rational and/or honest. Minding minds, a legitimate concern, can also make masking legitimately confusing. To disentangle the potential confusions, particularly, the ramifications of irrationality and dishonesty, here we resort to evolutionary game theory. Specifically, we formulate and analyze the masking problem with a fictitious pair of young lovers, Alice and Bob, as a Sir Philip Sydney (SPS) evolutionary game, inspired by the handicap principle in evolutionary biology and cryptography figures in computer science. With the proposed ABD (Alice and Bobs dating dilemma) as an asymmetric four-by-four strategic-form game, 16 strategic interactions were identified, and six of which may reach equilibriums with different characteristics such as separating, pooling, and polymorphic hybrid, being Nash, evolutionarily stable or neutrally stable. The six equilibrium types seem to mirror the diverse behaviors of mask believers, skeptics, converted, universal masking, voluntarily masking, coexisted and/or divided world of believers and skeptics. We suggest that the apparently simple ABD game is sufficiently general not only for studying masking policies for populations (via replicator dynamics), but also for investigating other complex decision-making problems with COVID-19 pandemic including lockdown vs. reopening, herd immunity vs. quarantines, and aggressive tracing vs. privacy protection.

category: public and global health


title: Protective efficacy of holed and aging PBO-pyrethroid synergist-treated nets on malaria infection prevalence in north-western Tanzania

abstract: Two billion pyrethroid long-lasting insecticidal nets (LLINs) have been distributed since 2010 for malaria prevention in Sub-Saharan Africa. Current malaria control strategies rely on an assumed effective 3-year lifespan for LLINs. PBO synergist LLINs are a newly recommended class but there is limited information on their life span and long-term protective efficacy in communities. To assess their operational survival, a cohort of 390 PBO LLINs (Olyset Plus) and 367 standard pyrethroid LLIN (Olyset net) from 396 households were followed for 36 months in Western Tanzania. To assess the association between the condition of the LLIN and malaria infection, nets from at least 480 randomly selected households were assessed during malaria prevalence cross-sectional surveys at 4, 9, 16, 21, 28, and 33 months post-distribution. Information on the presence and condition of nets, and demographic information from the household, were collected to evaluate factors influencing net durability. After 3 years less than 17% of nets distributed were available for sleeping. The fabric condition was not associated with malaria infection in either type of net. The difference between the net types was highest when nets were between 1-2 years old, when PBO nets appeared to be similarly protective as nets less than a year old, whereas standard nets were considerably less protective as they aged, regardless of fabric condition. There was no statistical difference in the estimated median functional survival time between net types with 1.6 years (95% CI 1.38-1.87) for PBO LLIN and 1.9 years (95% CI 1.67-2.06) for standard LLINs. After 3 years, there was a loss of 55% of permethrin content for both nets, and 97% of PBO content was lost in PBO LLIN. These results highlight that functional survival is less than the recommended 3 years for both net types. However, even as the nets age, the PBO nets remained more protective than standard nets, regardless of their condition.


title: Cycling for climate and public health: a missed opportunity for France

abstract: In addition to its potential contribution to reaching climate targets, cycling may generate substantial population-level health benefits through the physical activity it requires. Due to the lack of nationally representative mobility data, the health impact of current levels of cycling is still unknown for France. Relying on a health impact assessment framework and using recent nationally-representative data on mobility, we assessed the health and related economic benefits of cycling in 2018-2019 in France. We show that such benefits remain moderated and fall short when compared to those estimated in other countries with high cycling levels. We argue that cycling in France did not receive the attention and investments it deserves over the past decade and thus represents a missed opportunity for climate action and public health.


title: Animals in higher education settings: Do animal-assisted interventions improve mental and cognitive health outcomes of students?  A systematic review and meta-analysis

abstract:
BackgroundDue to the high burden of mental health issues among students at higher education institutions world-wide, animal-assisted interventions (AAIs) are being increasingly used to relieve student stress. The objective of this study was to systematically review of the effects of AAIs on the mental and cognitive health outcomes of higher education students.

MethodsRandomized controlled trials using any unfamiliar animal as the sole intervention tool were included in the systematic review. Study quality was assessed using the Cochrane Risk-of-Bias tool. Where possible, effect sizes (Hedges g) were pooled for individual outcomes using random-effects meta-analyses. Albatross plots were used to supplement the data synthesis.

ResultsOf 2.401 identified studies, 35 were included. Almost all studies used dogs as the intervention animal. The quality of most included studies was rated as moderate. Studies showed an overall reduction of acute anxiety (g= -0.57 (95%CI -1.45;0.31)) and stress. For other mental outcomes, studies showed an overall small reduction of negative affect (g= -0.47 (95%CI -1.46;0.52)), chronic stress (g= -0.23 (95%CI -0.57;0.11)) and depression, as well as small increases in arousal, happiness and positive affect (g= 0.06 (95%CI -0.78;0.90)). Studies showed no effect on heart rate and heart rate variability, a small reduction in salivary cortisol and mixed effects on blood pressure. No effect on cognitive outcomes was found.

ConclusionOverall, evidence suggests that AAIs are effective at improving mental, but not physiological or cognitive outcomes of students. Strong methodological heterogeneity between studies limited the ability to draw clear conclusions.


title: Profile of Brazilian inpatients with COVID-19 vaccine breakthrough infection and risk factors for unfavorable outcome

abstract:
ObjectiveTo characterize the epidemiological and clinical profile of individuals more likely to become infected by SARS-CoV-2 after the fully vaccination schedule in order to profile priority groups to receive a booster dose in situations of vaccine doses shortage as well as for maintenance of personal protective care.

MethodsData from hospitalized COVID-19 patients who had been fully vaccinated and had a SARS-CoV-2 infection positive diagnosis were collected from the SIVEP-Gripe database (Influenza Epidemiological Surveillance Information System) from January 18, 2021 to September 15, 2021. Demographic data, clinical symptoms/signs and preexisting medical conditions (comorbidities) were analyzed. The primary outcome was in-hospital death.

ResultsThe majority of hospitalized patients with vaccine breakthrough infection were elderly [≥] 60 years old, male, with critical or severe COVID-19. The fatality rate was extremely high (50.27%) and more pronounced in elderly groups. The most prevalent symptoms were cough, dyspnoea, respiratory distress, and low blood oxygen saturation. The most frequent comorbidities were heart disease and diabetes. High fatality rates were observed among patients admitted to the intensive care units (72.88%) and those who required invasive mechanical ventilation (87.82%). The main risk factors for an unfavorable outcome were older age, respiratory compromise, inactivated virus vaccine immunization, and preexisting medical conditions.

ConclusionsWe characterize the profile of hospitalized Brazilian patients with COVID-19 vaccine breakthrough infection and the risk factors for an unfavorable outcome. These data have made it possible to identify priority groups to receive a booster dose, in addition to not neglecting personal protection.


title: Poor Working Relationship between Doctors and Hospital Managers: A Systematic Review

abstract:
BackgroundThe problem of poor relationships between doctors and hospital managers is a common feature of many healthcare systems worldwide, including the United Kingdoms NHS. Despite the significant impact that a poor working relationship between doctors and managers could have on the quality of care, there is limited research in this area.

ObjectivesTo investigate the organisational factors, contributing to the poor working relationship between doctors and hospital managers with a view to recommend potential solutions to address them.

MethodsWe performed a systematic literature review; a comprehensive search of AMED, MEDLINE, CINAHL, plus with Full Text, SportDiscus and EBSCO EBooks from January 2000 to July 2019 and updated in March 2022, and no further article was found that meets the selection criteria. Mixed methods, qualitative studies and quantitative studies published in English language in peer reviewed journals between January 2000 and March 2022 were included. Study selection, data extraction and appraisal of study were undertaken by the authors. Quality criteria were selected from CASP Checklist.

ResultsA total of 49,340 citations were retrieved and screened for eligibility, 41 articles were assessed as full text and 15 met the inclusion criteria. These include 2 mixed method studies, 8 qualitative studies, and 5 quantitative studies. A thematic analysis was undertaken, and narrative summaries used to synthesise the findings.

ConclusionThe findings of this systematic review show strong evidence of poor collaboration and lack of effective communication that contribute to poor working relationships between physicians and hospital administrators. The results from this review may guide the development of a hospital plan that involves both doctors and managers in the decision making process regarding the quality of patient care, which could potentially enhance the relationship between the two groups as it would build trust between them.

O_TEXTBOXWhat is already known on this topicO_LIThe problem of poor relationships between doctors and hospital managers is a common feature of many healthcare systems worldwide.
C_LIO_LIDespite the significant impact this poor relationship could have on the quality of care and patient satisfaction, there is limited research in this area.
C_LI

What This Study AddsO_LIWe conducted a systematic review on the effect of tension between doctors and hospital managers on the quality of care provided in hospital or healthcare centres; 15 (qualitative, quantitative and mixed) primary papers were reviewed.
This qualitative systematic study found considerable evidence of organisational factors that contributes to poor working relationships between doctors and managers.
C_LI

C_TEXTBOX


title: Effectiveness of ChAdOx1 nCoV-19 Corona Virus Vaccine (CovishieldTM) in preventing SARS-CoV2 infection, Chennai, Tamil Nadu, India, 2021

abstract:
BackgroundIndia experienced the second wave of the COVID-19 pandemic in March 2021, driven by the delta variant. Apprehensions around the usefulness of vaccines against delta variant posed a risk to the vaccination program. Therefore, we estimated the effectiveness of two doses of the ChAdOx1 nCoV-19 (Covishield) vaccine against COVID-19 infection among individuals [≥]45 years in Chennai, India.

MethodsA community-based cohort study was conducted from May to September 2021 in a selected geographic area in Chennai, Tamil Nadu. The estimated sample size was 10,232. We enumerated individuals from all eligible households and periodically updated vaccination and COVID-19 infection data. We computed vaccine effectiveness with its 95% confidence interval for two doses of the Covishield vaccine against any COVID-19 infection.

ResultsWe enrolled 69,435 individuals, of which 21,793 were above 45 years. Two dose coverage of Covishield in the 18+ and 45+ age group was 18% and 31%, respectively. The overall incidence of COVID-19 infection was 1099 per 100,000 population. The vaccine effectiveness against COVID-19 disease in the [≥]45 age group was 61.3% (95% CI: 43.6 - 73.4) at least two weeks after receiving the second dose of Covishield. Genomic analysis of 74 (28 with two doses, 15 with one dose, and 31 with zero dose) out of the 90 aliquots collected from the 303 COVID-19 positive individuals in the 45+ age group showed delta variants and their sub-lineages.

ConclusionWe demonstrated the effectiveness of two doses of the ChAdOx1 vaccine against the delta variant in the general population of Chennai. We recommend similar future studies considering emerging variants and newer vaccines. Two-dose vaccine coverage could be ensured to protect against COVID-19 infection.


title: Medical Exemptions to Vaccination - Riverside County, California, 2016-2019

abstract:
ObjectivesTo review the nature and clinical reasoning of medical exemptions to vaccination received in Riverside County, CA after California Senate Bill 277 eliminated personal belief exemptions statewide.

Methods614 deduplicated medical exemptions to vaccination from 156 providers were reviewed from August 2016 to August 2019. Exemptions covering all vaccines were additionally coded for number and category of medical justification.

Results81.3% of reviewed exemptions were for all vaccines, 91.0% were permanent or indefinite, and 74.9% were for all vaccines and permanent or indefinite. Of the 490 evaluated all-vaccine exemptions, a median of two and maximum of ten justifications were cited per exemption, most often a family history of autoimmune disease other than allergy. Three providers wrote more than 70 exemptions each.

ConclusionsThe number and nature of the exemptions reviewed here raise concerns over their impact on immunization rates, and future policies may need to ensure additional oversight.


title: Monogenetic Rare Diseases in Biomedical Databases and Text Mining

abstract: 1AO_SCPLOWBSTRACTC_SCPLOWThe testing of pharmacological hypotheses becomes faster and more accurate, but at the same time more difficult than even two decades ago. It takes more time to collect and analyse disease mechanisms and experimental facts in various specialized resources. We discuss a new approach to aggregating individual pieces of information about a single disease using Elseviers automated text mining technology. Developed algorithm allows for the collection of published facts in a unified format starting only with the name of the disease. The special template, which combines research and clinical descriptions of diseases was developed. The approach was tested, and information was collected for 55 rare monogenic diseases. Clinical, molecular, and pharmacological characteristics of diseases with supporting references from the literature are available in the form of tables and files. Manually curated templates for 10 rare diseases, including top ranked Cystic Fibrosis and Huntingtons disease, were published to demonstrate the results of the described approach.

category: medical education


title: Memory and Concentration Skills In A Sample of First Grade Medical Students at University of Baghdad/College of Medicine

abstract:
ObjectivesThe purpose of this study is to assess the level of memory skills and concentration skills among first year medical students in College of Medicine/University of Baghdad depending on global scale (Study Skills Inventory SSI).

Subjects and MethodA cross-sectional study to assess memory and concentration skills among first year medical students in College of Medicine/ University of Baghdad, the study was conducted using an online survey in September 2020. A sample of 103 students participated in the study by filling of an online questionnaire which was modified from the Study Skills Inventory (SSI).

Regarding memory skills a score less than 30 was considered not adequate, while regarding concentration skills a score less than 35 was considered not adequate.

ResultsPercentage of males was 68% and the percentage of females was 32%. About studying hours we found that 59.2% students study less than 3 hours, 25.2% students study between 3-6 hours and 15.5% students study more than 6 hours. The mean score of the students for concentration skills was 36.45 and was 32.40 for memory skills. Regarding concentration skills 35% students had non adequate score and 65% students had adequate score, regarding memory skills 28.2% students had non adequate score and 71.8% students had adequate score. There is a statistically significant association between concentration skills and studying hours and there is statistically significant association between memory skills and studying hours. There was a statistically significant moderate positive correlation between concentration skill score and the memory skill score of the students total score (r = 0.511, p < 0.01).

ConclusionAbout 75% of 1st year medical students have adequate concentration and memory skills. The students who study for 3-6 hours daily have the least mean score of both skills with 42.3% of them have adequate concentration skills score and 57.7% had adequate memory skills score. Further studies with larger sample size are needed to correlate the concentration and memory skills with student end year average total score.


title: Addition of formaldehyde releaser imidazolidinyl urea and MOPS buffer to urine samples enables delayed processing for flow cytometric analysis of urinary cells

abstract:
Kidney diseases are a major health concern worldwide. Currently there is a large unmet need for novel biomarkers to non-invasively diagnose and monitor kidney diseases. Urinary cells are promising biomarkers and their analysis by flow cytometry has demonstrated its utility in diverse clinical settings. However, up to date this methodology depends on fresh samples, as cellular event counts and the signal-to-noise-ratio deter over time.

Here we developed an easy-to-use two-step preservation method for conservation of urine samples for subsequent flow cytometry. The protocol utilizes a combination of the formaldehyde releasing agent imidazolidinyl urea (IU) and MOPS buffer, leading to gentle fixation of urinary cells. The preservation method increases acceptable storing time of urine samples from several hours to up to 6 days. Cellular event counts and staining properties of cells remain comparable to fresh untreated samples.

The hereby presented preservation method facilitates future investigations on flow cytometry of urinary cells as potential biomarkers and may enable broad implementation in clinical practice.

category: nephrology


title: Multiple Cost Optimisation for Alzheimer's Disease Diagnosis

abstract:
Current machine learning techniques for dementia diagnosis often do not take into account real-world practical constraints, which may include, for example, the cost of diagnostic assessment time and financial budgets. In this work, we built on previous cost-sensitive feature selection approaches by generalising to multiple cost types, while taking into consideration that stakeholders attempting to optimise the dementia care pathway might face multiple non-fungible budget constraints. Our new optimisation algorithm involved the searching of cost-weighting hyperparameters while constrained by total budgets. We then provided a proof of concept using both assessment time cost and financial budget cost. We showed that budget constraints could control the feature selection process in an intuitive and practical manner, while adjusting the hyperparameter increased the range of solutions selected by feature selection. We further showed that our budget-constrained cost optimisation framework could be implemented in a user-friendly graphical user interface sandbox tool to encourage non-technical users and stakeholders to adopt and to further explore and audit the model -a humans-in-the-loop approach. Overall, we suggest that setting budget constraints initially and then fine tuning the cost-weighting hyperparameters can be an effective way to perform feature selection where multiple cost constraints exist, which will in turn lead to more realistic optimising and redesigning of dementia diagnostic assessments.

Clinical RelevanceBy optimising diagnostic accuracy against various costs (e.g. assessment administration time and financial budget), predictive yet practical dementia diagnostic assessments can be redesigned to suit clinical use.

category: neurology


title: Intellectual enrichment and genetic modifiers of cognitive function in Huntington's disease

abstract: An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntingtons disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle, and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntingtons disease. For this purpose, we analysed data from Track- HD, a multi-centre longitudinal study in Huntingtons disease gene-carriers, and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared to non-carriers, in agreement with its role in somatic expansion instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, ie. those who were better educated, had higher verbal IQ and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntingtons disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non- carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than non- carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntingtons disease and their mechanism of action.


title: Effect of fasting therapy on vitamin D, vitality and quality of life. A randomized control trial

abstract:
BackgroundThe aim of the present study was to determine the effects of prolonged fasting (10 days) in the vitamin D, B12 levels, body mass index (BMI), weight, hemoglobin, vitality and quality of life (QoL) compared to normal diet.

MethodsThis randomized control trial included 52 participants (aged 19-74 years) randomized in to a fasting group (FG) or a normal diet group (NDG) with 26 participants in each group. The study was conducted at an in-patient setting where the FG were on a fasting diet (500 kCal/day) which included holy basil herbal tea, lemon honey juice and water (3 L). The NDG (1500 kCal/day) consumed routine diet that included Indian breads, pulses, steamed rice, vegetable salads and beverages.

ResultsThe FG has shown significant increase in the Vitamin D levels (p=0.003, d=0.475), vitality (p=0.006, d=0.425), physical QoL (p<0.001, d=0.549), psychological QoL (p=0.002, d=0.488), environmental QoL (p=0.004, d=0.457) compared to NDG. No significant changes were observed in Vitamin B12, weight, BMI, hemoglobin and social QoL. A weak to moderate ({rho}= 0.330-0.483) positive correlation was observed between vitality scores and QoL domains, whereas BMI scores showed an inverse correlation ({rho}=-0.280) with vitamin D levels.

DiscussionThe results suggest that prolonged fasting can improve the vitamin D levels, vitality and promote quality life compared to normal diet. Unlike previous studies FG does not differ from NDG with respect to weight and BMI. Nevertheless, fasting may be utilized as an effective tool to tackle vitamin d deficiency and associated health insufficiencies.

Trial RegistryClinical Trial Registry of India CTRI/2022/02/040446.

category: nutrition


title: Impact of a Multidisciplinary Nutritional Support Team (MNST) on Quality Improvement in Home Parenteral Nutrition (HPN)

abstract:
IntroductionHPN is essential for patients requiring long term nutritional support. This Quality Improvement Project for HPN Patients (QIP-PN) studied the effect of a Physician Nutrition Expert (PNE)- led multidisciplinary nutritional support team (MNST) on HPN care.

ObjectiveTo test the effect of an MNST on adherence to protocols, outcomes and QOL in HPN.

MethodsData review was conducted in phases 1a and 1b, observation in phase 2 and intervention in phase 3. In Phase 3 the MNST made recommendations to treating physicians. All long-term HPN patients were offered study participation. 75 signed consent forms. Treating physician study participation agreements were signed for 42 patients (the study group). A random sample of 30 long-term HPN patients comprised the case-matched control group (control). Data were collected on demographics, treating physicians PNE status, HPN care variables, recommended interventions, quality-of-life assessment, adverse outcomes and hospitalizations. Independent samples t-test was used for continuous data between study group and control group. Paired t-test was used for phase 2 and phase 3 patient data. Comparison between the study and control group utilized a negative binomial regression model. Statistical analysis utilized R (https://www.r-project.org/).

Results34 patients were reviewed retrospectively in phase 1a and 197 prospectively in phase 1b. 40 study patients completed phase 2 and progressed into phase 3, of whom 30 completed [≥]60 therapy days. Improvements in weight, BMI and QOL were seen in the study patients during intervention. Recommendations made and accepted by treating physicians differed based on PNE status. Study patients had fewer adverse outcomes and related hospitalizations than case matched controls.

ConclusionMNST recommendations improved clinical, biochemical parameters and patients self-reported overall health. It reduced adverse outcomes, hospitalization and hospital length of stay. MNST input could have a significant impact on the quality and cost of HPN care.


title: Impact of a Multidisciplinary Nutritional Support Team on Quality Improvement in Home Parenteral Nutrition


title: Protocol for the pilot study of group video yogic breathing app in breast cancer survivors

abstract:
IntroductionBreast cancer remains a leading cause of cancer deaths; however, recent improvements in treatment have improved survivorship. As a result of this improvement, more individuals are living with the long-term side effects of cancer treatment. Therefore, methods that incorporate lifestyle and mind-body approaches are becoming increasingly used in the patient treatment pathway.

MethodsIn this study, PranaScience Institute will develop and test a group video mobile application for Yogic Breathing (YB). YB is shown to reduce symptomatic conditions associated with several conditions including breast cancer. For this initial feasibility study, PranaScience will collaborate with the Medical University of South Carolina to implement the study app-based program in breast cancer survivors. This research is aimed to understand if the YB could be delivered via an app, if participants are able to practice it satisfactorily, and if there is any symptom relief by the YB practice. In the control group, participants will be directed to the Attention Control (AC) feature of the app, which guides users to focus on a mindfulness activity not involving YB. Participants will be randomly assigned to the YB or AC study plan (N=20 per group). Breast cancer survivors who have completed radiation therapy within last 6 months will be recruited for this study and provided access to the app for a 12-week program. The study app will record total practice times. Virtual visits by a study yoga instructor during group video sessions will measure participant compliance with proper technique. Feasibility will be examined by evaluating intervention delivery factors and resource needs. Acceptability of using the mobile study app to support symptom management will be evaluated using a satisfaction and system usability scale. Behavioral survey measures will help guide effect sizes and power calculations for the next larger-scale study. Biomarkers in the saliva (tumor suppressors, cytokines), and fingernails (cortisol, differential proteomics) will be measured at baseline and end of study at 12 weeks.

DiscussionAll findings from this pilot study will be synthesized to refine the mobile study app in preparation for large-scale evaluation in Phase II involving all-study site participants with cancer. ClinicalTrials.gov Identifier NCT05161260.

category: oncology


title: Comparison of the accuracy of 9 intraocular lens power calculation formulas using partial coherence interferometry

abstract:
PurposeTo compare the accuracy of 9 intraocular lens (IOL) power calculation formulas (SRK/T, Hoffer Q, Holladay 1, Haigis, Barrett Universal II, Kane, EVO 2.0, Ladas Super formula and Hill-RBF 3.0) using partial coherence interferometry (PCI).

MethodsData from patients having uncomplicated cataract surgery with the insertion of 1 of 3 IOL types were included. All preoperative biometric measurements were performed using PCI. Prediction errors (PE) were deduced from refractive outcomes evaluated 3 months after surgery. The mean prediction error (ME), mean absolute prediction error (MAE), median absolute prediction error (MedAE), and standard deviation of prediction error (SD) were calculated, as well as the percentage of eyes with a PE within {+/-}0.25, {+/-}0.50, {+/-}0.75 and {+/-}1.00D for each formula.

ResultsIncluded in the study were 126 eyes of 126 patients. Kane achieved the lowest MAE and SD across the entire sample as well as the highest percentage of PE within {+/-}0.50D, and was proven to be more accurate than Haigis and Hoffer Q (P <.001). For an axial length of more than 26.0 mm, EVO 2.0 and Barrett obtained the lowest MAEs, with EVO 2.0 and Kane showing a higher percentage of prediction at {+/-}0.50D compared to old generation formulas except for SRK/T (P =.04).

ConclusionAll investigated formulas achieved good results; there was a tendency towards better outcomes with new generation formulas, especially in atypical eyes.

category: ophthalmology


title: SYSTEMATIC REVIEW EXPLORING THE IMPACT OF SOCIO-CULTURAL FACTORS ON PAIN MANAGEMENT APPROACHES IN SUB- SAHARAN AFRICA

abstract:
AimThe experience and expression of pain are influenced by numerous factors of which culture and the society plays a major role especially in SSA. However, few studies have focused on the impact of cultural influences on pain assessment and management in SSA. This systemic review examines pain prevalence and its intensity/severity, the socio-cultural factors that affect pain management and the extent to which socio-cultural practices influence pain assessment and management in SSA.

MethodsApplying the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was conducted. Seven electronic databases were searched, and a strict inclusion and exclusion criteria applied to the retrieve articles along with a robust filtering to identify eligible peer reviewed literature. The review process concluded with 24 eligible articles and following the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach was applied to assess the quality of the included literature and thematic narrative analysis was conducted.

ResultsThe analysis findings identified that there are sociocultural barriers to effective pain management from the perspective of different subcultures in SSA. The evidence suggests that religious/spiritual and inherited beliefs, along with limited knowledge and health literacy influence the experience and pain management approaches applied in SSA. In addition, results indicate that, resource constraints and cultural and societal norms impact on access and use of pain management among the population in SSA.

ConclusionHealthcare professionals should be aware of how the society, cultural and beliefs of their patients influence their expression of pain and subsequent pain management. Under-treatment or over-treatment might occur if health workers are unaware or do not consider the cultural norms associated with pain and pain expression, due to the subjective and individual nature of pain.

category: pain medicine


title: Exploring the genetic overlap between 12 psychiatric disorders

abstract: The widespread comorbidity among psychiatric disorders (PDs) demonstrated in epidemiological studies1-5 is mirrored by non-zero, positive genetic correlations from large scale genetic studies6-10. We employed several strategies to uncover pleiotropic SNPs, genes and biological pathways7,8 underlying this genetic covariance. First, we conducted cross-trait meta-analysis on 12 PDs to identify pleiotropic SNPs. However, the majority of meta-analytic signal was driven by only one or a few PDs, hampering interpretation and joint biological characterization of the meta-analytic signal. Next, we performed pairwise comparisons of PDs on the SNP, gene, genomic region, gene-set, tissue-type, and cell-type level. Substantial overlap was observed, but mainly among pairs of PDs, and mainly at less stringent p-value thresholds. Only heritability enrichment for "conserved genomic regions" and "nucleotide diversity" was significant for multiple (9 out of 12) PDs. Overall, identification of shared biological mechanisms remains challenging due to variation in power and genetic architecture between PDs.

category: genetic and genomic medicine


title: The Contributions of Rare Inherited and Polygenic Risk to ASD in Multiplex Families

abstract: Autism Spectrum Disorder (ASD) has a complex genetic architecture involving contributions from de novo and inherited variation. Few studies have been designed to address the role of rare inherited variation, or its interaction with polygenic risk in ASD. Here, we performed whole genome sequencing of the largest cohort of multiplex families to date, consisting of 4,551 individuals in 1,004 families having 2 or more affected children with ASD. Using this study design, we identify seven novel risk genes supported primarily by rare inherited variation, finding support for a total of 74 genes in our cohort and a total of 152 genes after combining with other studies. Probands demonstrated an increased burden of mutations in 2 or more known risk genes (KARGs) -- in three families both probands inherited protein truncating variants in two KARGs. We also find that polygenic risk is over transmitted from unaffected parents to affected children with rare inherited variants, consistent with combinatorial effects in the offspring, which may explain the reduced penetrance of these rare variants in parents. We also observe that in addition to social dysfunction, language delay is associated with ASD polygenic risk over-transmission. These results are consistent with an additive complex genetic risk architecture of ASD involving rare and common variation and further suggest that language delay is a core biological feature of ASD.


title: COVID-19 relevant genetic variants confirmed in an admixed population

abstract:
The dissection of factors that contribute to COVID-19 infection and severity has overwhelmed the scientific community for almost 2 years. Current reports highlight the role of in disease incidence, progression, and severity. Here, we aimed to confirm the presence of previously reported genetic variants in an admixed population. Allele frequencies were assessed and compared between the general population (N=3079) for which at least 30% have not been infected with SARS-CoV2 as per July 2021 versus COVID-19 patients (N=106).

Genotyping data from the Illumina GSA array was used to impute genetic variation for 14 COVID-relevant genes, using the 1000G phase 3 as reference based on the human genome assembly hg19, following current standard protocols and recommendations for genetic imputation. Bioinformatic and statistical analyses were performed using MACH v1.0, R, and PLINK.

A total of 7953 variants were imputed on, ABO, CCR2, CCR9, CXCR6, DPP9, FYCO1, IL10RB/IFNAR2, LZTFL1, OAS1, OAS2, OAS3, SLC6A20, TYK2, and XCR1. Statistically significant allele differences were reported for 10 and 7 previously identified and confirmed variants, ABO rs657152, DPP9 rs2109069, LZTFL1 rs11385942, OAS1 rs10774671, OAS1 rs2660, OAS2 rs1293767, and OAS3 rs1859330 p<0.03. In addition, we identified 842 variants in these COVID-related genes with significant allele frequency differences between COVID patients and the general population (p-value <E-2 - E-179).

Our observations confirm the presence of genetic differences in COVID-19 patients in an admixed population and prompts for the investigation of the statistical relevance of additional variants on these and other genes that could identify local and geographical patterns of COVID-19.


title: The genetic background of hydrocephalus in a population-based cohort: implication of ciliary involvement

abstract:
BackgroundHydrocephalus is one of the most common congenital disorders of the central nervous system and often displays psychiatric co-morbidities, in particular autism spectrum disorder. The disease mechanisms behind hydrocephalus are complex and not well understood, but some association with dysfunctional cilia in the brain ventricles and subarachnoid space has been indicated. A better understanding of the genetic aetiology of hydrocephalus, including the role of ciliopathies, may bring insights into a potentially shared genetic aetiology. In this population-based case-cohort study we, for the first time, investigated variants of postulated hydrocephalus candidate genes. Using this data, we aimed to investigate potential involvement of the ciliome in hydrocephalus and describe genotype-phenotype associations with autism spectrum disorder, identified in the iPSYCH cohort.

MethodsOne-hundred and twenty-one hydrocephalus candidate genes were screened in a whole-exome sequenced sub cohort of the iPSYCH study, comprising 72 hydrocephalus patients and 4,181 background population controls. Candidate genes containing high-impact variants of interest were systematically evaluated for their involvement in ciliary function and autism spectrum disorder.

ResultsThe median age at diagnosis for the hydrocephalus patients was 0 years of age (range 0-27 years), the median age at analysis was 22 years (11-35 years), and 70.5 % were males. Median age for controls was 18 years (range 11-26 years) and 53.3 % were males. Fifty-two putative hydrocephalus-associated variants in 34 genes, were identified in 42 patients (58.3 %). In hydrocephalus cases, we found increased, but not significant, enrichment of high-impact protein altering variants (OR 1.51, 95% CI 0.92-2.51, p = 0.096), which was driven by a significant enrichment of rare protein truncating variants (OR 2.71, 95% CI 1.17-5.58, p = 0.011). Fourteen of the genes with high-impact variants are part of the ciliome, whereas another six genes affect cilia-dependent processes during neurogenesis. Furthermore, 15 of the 34 genes with high-impact variants and three of eight genes with protein truncating variants were associated with autism spectrum disorder.

ConclusionsBecause symptoms of other diseases may be neglected or masked by the hydrocephalus-associated symptoms and identification of co-morbidities may be of clinical significance, we suggest that patients with congenital hydrocephalus undergo clinical genetic assessment with respect to ciliopathies and autism spectrum disorder. Our results point to the significance of hydrocephalus as a ciliary disease in some cases. Future studies in brain ciliopathies may not only reveal new insights into hydrocephalus, but also, brain disease in the broadest sense, given the essential role of cilia for neurodevelopment.


title: Triangulating evidence in health sciences with Annotated Semantic Queries

abstract: Integrating information from data sources representing different study designs has the potential to strengthen evidence in population health research. However, this concept of evidence "triangulation" presents a number of challenges for systematically identifying and integrating relevant information. We present ASQ (Annotated Semantic Queries), a natural language query interface to the integrated biomedical entities and epidemiological evidence in EpiGraphDB, which enables users to extract "claims" from a piece of unstructured text, and then investigate the evidence that could either support, contradict the claims, or offer additional information to the query. This approach has the potential to support the rapid review of pre-prints, grant applications, conference abstracts and articles submitted for peer review. ASQ implements strategies to harmonize biomedical entities in different taxonomies and evidence from different sources, to facilitate evidence triangulation and interpretation. ASQ is openly available at https://asq.epigraphdb.org.

category: health informatics


title: Mondo: Unifying diseases for the world, by the world

abstract: There are thousands of distinct disease entities and concepts, each of which are known by different and sometimes contradictory names. The lack of a unified system for managing these entities poses a major challenge for both machines and humans that need to harmonize information to better predict causes and treatments for disease. The Mondo Disease Ontology is an open, community-driven ontology that integrates key medical and biomedical terminologies, supporting disease data integration to improve diagnosis, treatment, and translational research. Mondo records the sources of all data and is continually updated, making it suitable for research and clinical applications that require up-to-date disease knowledge.


title: The impact of HIV on women living with HIV and their families in low- and middle-income countries: A systematic review

abstract: HIV infection adds a significant burden to women in low- and middle-income countries (LMICs), often leading to severe detrimental impact, not only on themselves, but also on their families and communities. Given that more than half of all people living with HIV globally are females (53%), this review seeks to understand the impact of HIV infection on women living with HIV (WLHIV) and their families in LMICs, and the interrelationships between one impact and another. A systematic review was conducted to find literature using the following databases: Medline, PsycINFO, CINAL, Emcare, Scopus and ProQuest. Research articles were included if they met the following inclusion criteria: conducted in LMICs, published in English language between January 1st 1990 and October 31st 2021, had full text available, involved WLHIV (married and unmarried), and focused on the impact of HIV on these women and their families. Critical appraisal tools developed by Joanna Briggs Institute (JBI) were used to assess the methodological quality of the studies and thematic narrative synthesis was used to analyse the findings. A total of 22 articles met the inclusion criteria. The review showed that HIV has a range of negative consequences on WLHIV and their families including: (i) psychological impact, (ii) poor physical health and intimate partner violence, (iii) social impact, and (iv) economic impact. The findings indicate the need for targeted interventions, specific to WLHIV, that address the inequity and discrimination they face. These interventions should also incorporate education and sustainable support structures for WLHIV and their families.

category: hiv aids