title: Adequacy Of Salt Iodization, Retailers Knowledge And Associated Factors About Iodized Salt In Oromia Special Zone Surrounding Finfinne, Ethiopia

abstract:
BackgroundThere are laws to enforce the universal iodization of salt to check the consequences of iodine deficiency in Ethiopia. These laws are to ensure that there are production and sales of iodized salt in the country. Yet, the adequacy of iodized salt in the retailers level is not determined.

ObjectiveThis study is aimed to investigate the adequacy of salt iodization, retailers knowledge, and associated factors about iodized salt among retailers in Addis Ababa surrounding finfinne Special Zone, Ethiopia.

MethodsA community-based cross-sectional study was conducted among 202 iodized salt retailers that were selected by using a simple random sampling technique. Data among the shop retailers for the assessment of knowledge was collected by using a structured questionnaire, and titration test method was done to determine the adequacy of salt iodization. The data management and analysis were done by using Statistical Packages for Social Scientists Version 23. Descriptive statistics such as mean, median, standard deviation, and frequency were computed to describe the data. Binary logistic regression analysis was done to examine the association between the dependent and independent variables. The strength of association between the dependent and independent variables was explained by using the odds ratio and the level of statistical significance was accepted at a p-value of less than 0.05. Finally, the results were presented by using graphs and tables.

ResultA total of 202 salt retailers were approached in this study with a mean age of 28.78{+/-}7.548 years. Nearly around two-thirds of the study participants were male. Of the total retailers salt samples, 95(57.2%) were adequately (20-40ppm) iodized, and the educational level of the retailers was significantly associated with the adequacy of salt iodization. From the total salt retailer, 113(55.9%) had good knowledge, and retailers who heard about iodized salt (AOR=0.043, CI: 0.017-0.109, p<0.001) and having legal framework/law (AOR=0.24, CI: 0.098-0.61, p=0.003) that prohibits the selling of non-iodized salt were significantly associated with good knowledge level.

Conclusion and RecommendationStill policies have been implemented to promote the production and consumption of iodized salt, the iodine content of salt in retail shops in the Oromia Special Zone Finfinne, Oromia regional state is not encouraging. We recommend the establishment of checkpoints along the production and distribution chain to ensure salt with adequate iodine reaches the consumer. Again, traders of iodized salt should have regular training on ways to preserve salt to maintain its iodine content


title: One-year results of long femoropopliteal lesions stenting with fasciotomy lamina vastoadductoria

abstract:
ObjectiveFasciotomy can increase the mobility of the superficial femoral artery and reduce the incidence of stent breakage. This study aimed to compare the long-term patency of drug-eluting nitinol stents with and without fasciotomy in patients with prolonged SFA occlusions.

MethodsA randomized clinical trial was conducted in 60 (1:1) patients with long femoropopliteal steno-occlusive lesions more than 200 mm. Patients in group 1 (Zilver) underwent recanalization of occlusion of the femoropopliteal artery with stenting. In group 2 (ZilverFas), recanalization of the femoropopliteal occlusion with stenting and fasciotomy of Gunters canal were performed. The follow up evaluation of patency at 6, 12 months.

Results12-month primary patency in Zilver and ZilverFas groups was 51% and 80%, respectively (p = 0.02). The freedom from target revascularization (TLR) in Zilver and ZilverFas groups was 50% and 76%, respectively (p = 0.04). At one-years, primary-assisted and secondary patency for the ZilverFas and Zilver groups were 83% versus 62% (p = 0.07), 86% versus 65% (p = 0.05), respectively. In groups Zilver and ZilverFas, the number of stents fracture was 14 and 7, respectively (p = 0.05). The Cox multivariables regression indicated that the stent fracture, diabetes mellitus were the independent predictor of restenosis and reocclusion. Fasciotomy reduced the chance of reocclusion and restenosis by 2.94 times.

ConclusionsOur study has shown that a decompressing the stented segment with fasciotomy significantly improves the patency of the femoropopliteal segment and significantly reduces the number and severity of stents fractures.

category: surgery


title: Exploring the use of UmbiFlow to assess the impact of heat stress on fetoplacental blood flow in field studies.

abstract:
ObjectiveTo evaluate the impact of heat stress on umbilical artery resistance index (RI) measured by UmbiFlow in field settings and the implications for pregnancy outcomes.

MethodsThis feasibility study was conducted in West Kiang, The Gambia, West Africa; a rural area with increasing exposure to extreme heat. We recruited women with singleton fetuses who performed manual tasks (such as farming) during pregnancy. The umbilical artery RI was measured at rest, during and at the end of a typical working shift in women [≥] 28 weeks gestation. Adverse pregnancy outcomes (APO) were classified as stillbirth, preterm birth, low birth weight, or small for gestational age, and all other outcomes as normal.

ResultsA total of 40 participants were included; 23 normal births and 17 APO. Umbilical artery RI demonstrated a nonlinear relationship to heat stress, with indication of a potential threshold value for placental insufficiency around 32{o}C by universal thermal climate index. Preliminary evidence suggests the fetoplacental circulation response to heat stress differs in APO versus normal outcome.

ConclusionsThe Umbiflow device proved to be an effective field method for assessing placental function. Dynamic changes in RI may begin to explain the association between extreme heat and APO.

FundingThe Wellcome Trust (216336/Z/19/Z)

SynopsisExtreme heat exposure is increasing and a low-cost umbilical artery doppler device, UmbiFlow, can aid understanding of fetoplacental function under heat stress conditions.

category: obstetrics and gynecology


title: Undernutrition and associated factors among people living with HIV under NACS assessment in Muchinga Province, Zambia, 2019-2020

abstract:
IntroductionGood nutrition in People Living with HIV (PLHIV) has a good influence on treatment outcomes and in turn a better quality of life. Despite, the significant role it plays, many patients have limited access to Nutritional Assessment Counselling and Support (NACS). We evaluated undernutrition in people living with HIV and associated factors in Muchinga Province, Zambia, from October 2019 to March 2020.

Material and MethodsThis was secondary analysis of routine program data of HIV-positive clients on ART enrolled at EQUIP-supported health facilities in Muchinga. Undernutrition was determined using body mass index (BMI) calculations and classified as undernutrition (<18.5 kg/m2), normal (18.5 - 24.9 kg/m2) or over-nutrition (overweight, 25 - 29.9 kg/m2 and obese, 25 - 29.9 kg/m2). Multivariate-adjusted odds ratios (aOR) were used to assess factors associated with undernutrition.

ResultsOf the 506 eligible clients under NACS, the mean age was 34.9 years {+/-} 13.5SD, with 251 (approximately 50%) between the ages of 21 - 39 years. More than half (67%) were females, 284 (56%) were urban residents, and 180 (35.6 %) were unemployed. The majority (approximately 71%) were on the TLE regimen with a median duration on ART treatment of [~]3 years (IQR=1- 6). There were 233 (46%) who had a normal BMI, 191 (37.7%) who had under-nutrition, and 82 (16.2%) who had over-nutrition (9.7% overweight: 6.5% obesity). Clients in the urban area (aOR= 2.0; 95%CI: 1.28 - 3.1), unemployed (aOR= 2.4 (1.18-4.69)2.4; 95%CI: 1.18 - 4.69), married (aOR= 2.3; 95%CI: 1.26 - 4.38) and being on TLD (aOR= 2.8; 95%CI: 1.23 - 6.23) were more likely to be under-nourished.

ConclusionNACS played a vital role in identifying HIV-positive clients who required more specialized care for improved clinical health outcomes. There is a need to strengthen HIV and nutrition integration in low-resourced countries with high HIV burden for improved treatment outcomes and quality of life.

category: hiv aids


title: Combinatorial language parent-report score differs significantly between typically developing children and those with Autism Spectrum Disorders

abstract: Prefrontal synthesis (PFS) is a component of constructive imagination. It is defined as the process of mentally juxtaposing objects into novel combinations. For example, to comprehend the instruction "put the cat under the dog and above the monkey," it is necessary to use PFS in order to correctly determine the spatial arrangement of the cat, dog, and monkey with relation to one another. The acquisition of PFS hinges on the use of combinatorial language during early development in childhood. Accordingly, children with developmental delays exhibit a deficit in PFS, and frequent assessments are recommended for these individuals. In 2018, we developed the Mental Synthesis Evaluation Checklist (MSEC), a parent-reported evaluation designed to assess PFS and combinatorial language comprehension. In this manuscript we use MSEC to identify differences in combinatorial language acquisition between ASD (N=29138) and neurotypical (N=111) children. Results confirm the utility of the MSEC in distinguishing language deficits in ASD from typical development as early as 2 years of age (p<0.0001).

category: pediatrics


title: Temporal trends in the incidence of haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003-2018

abstract:
BackgroundHaemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality and is increasingly being diagnosed. Little is known about what is driving the apparent rise in the incidence of this disease.

MethodsUsing national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between 1/1/2003 and 31/12/2018 were identified using a previously validated approach. We calculated incidence rates of diagnosed HLH per million population using mid-year population estimates by calendar year, age group, sex and associated comorbidity (haematological malignancy, inflammatory rheumatological or bowel diseases (IBD)) associated with the diagnosis of HLH. We modelled trends in incidence and the interactions between calendar year, age and associated comorbidity using Poisson regression.

FindingsThere were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (Incidence Rate Ratio (IRR) 2018 compared to 2003: 3.88 95% Confidence Interval (CI) 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11 95% CI 1.09 to 1.12). There was a rising trend in all age groups except those aged less than 5 years. There was a transition across the age groups with greater increases in those aged 5 to 14 years of HLH associated with rheumatological disease/IBD compared to HLH associated with haematological malignancy, with similar increases in HLH associated with both co-morbidities for those 15-54, and greater increases in associated haematological malignancies for those 55 years and older.

InterpretationThe incidence of HLH in England has quadrupled between 2003 and 2018, increasing 11% annually. Substantial variation in the incidence occurred by age group and by HLH associated comorbidities with inflammatory rheumatological diseases or IBD associated HLH increasing more among the young and middle age groups, whereas in older age groups the largest increase was seen with haematological malignancy-associated HLH.

Evidence before this studyThere is a paucity of population-based data on the epidemiology of HLH worldwide. The available evidence relies mostly upon a collection of cases series published in The Lancet in 2014 which described 2197 cases of HLH in adults reported in the literature to that point. Almost all of these were from tertiary referral specialist centres and/or described in small case series. The incidence of HLH has only been described in a few reports - and mainly this has focused on children with primary HLH. No previous studies have been large enough to examine trends in incidence by age, sex, underlying risk factors and calendar time.

Added value of this studyThis study quantifies the incidence of diagnosed HLH for the first time in a nationwide manner for all age groups. It reports on 1674 patients with HLH from England and shows that there is substantial variation in the incidence by age group, associated disease and calendar time. The results imply reasons for the increase in HLH could be related to the increasing occurrence of haematological cancer, inflammatory rheumatological or bowel diseases and the treatments given for these conditions. This study has been carried out in partnership with the National Congenital Anomalies and Rare Diseases Registration Service and the methodology described can in future be applied to many rare diseases that as yet lack a way of quantifying crucial epidemiological metrics.

Implications of all the available evidenceThe incidence of HLH is rising rapidly in people older than 5 years of age. This could be due to an increase in the biologic, immunomodulation or immunosuppressive therapy being used in people with haematological cancer and inflammatory rheumatological and bowel diseases. Further work should focus on how to minimise the risk of HLH occurring, or to improve treatment of this often fatal disease among those who need treatment for an associated comorbidity.

category: hematology


title: Proteasome inhibition enhances myeloma oncolytic reovirus therapy by suppressing monocytic anti-viral immune responses

abstract: Reovirus is an oncolytic virus with natural tropism for cancer cells. We previously showed that reovirus intravenous administration in myeloma patients was safe, but disease control associated with viral replication in the cancer cells was not observed. Here we show that ex vivo proteasome inhibitors (PIs) potentiate reovirus replication in circulating classical monocytes, increasing viral delivery to myeloma cells. We found that the anti-viral signals in monocytes primarily rely on the NF-kB activation and that this effect is impaired by the addition of PIs. Conversely, PIs improved reovirus-induced monocyte and T cell activation against cancer cells. Based on these preclinical data, we conducted a phase 1b trial of the reovirus Pelareorep together with the PI carfilzomib in 13 heavily pretreated bortezomib-resistant MM patients. Objective responses associated with reovirus active replication in MM cells, T cell activation and monocytic expansion were noted in 70% of patients.

category: oncology


title: Effect of Heat inactivation and bulk lysis on Real-Time Reverse Transcription PCR Detection of the SARS-COV-2: An Experimental Study

abstract: The outbreak of the severe acute respiratory syndrome coronavirus - 2 has quickly turned into a global pandemic. Real-time reverse transcription Polymerase chain reaction is commonly used to diagnose as "gold standard". Many coronaviruses are sensitive to heat and chemicals. Heat and chemical inactivation of samples is considered a possible method to reduce the risk of transmission, but the effect of heating and chemical treatment on the measurement of the virus is still unclear. Thus, this study aimed to investigate the effect of heat inactivation and chemical bulklysis on virus detection. The laboratory-based experimental study design was conducted in Ethiopian Public Health Institute from August to November 2020 on the samples referred to the laboratory for Coronavirus disease-19 testing. Tests were performed on eighty Nasopharyngeal/Oropharyngeal swab samples using the Abbott Real-time severe acute respiratory syndrome coronavirus - 2 assays, a test for the qualitative detection of virus in the sample. Data were analyzed and described by mean and standard deviation. Repeated measurement analysis of variance was used to assess the mean difference between the three temperatures and bulk lysis on viral detection. Post-hock analysis was employed to locate the place of significant differences. P-values less than 0.05 was used to declare statistical significance. About 6.2% (5/80) of samples were changed to negative results in heat inactivation at 60{degrees}C and 8.7% (7/80) of samples were changed to negative in heat inactivation at 100{degrees}C. The Cyclic threshold values of heat-inactivated samples (at 60{degrees}C, at 100{degrees}C, and bulk lysis) were significantly different from the temperature at 56{degrees}C. The efficacy of heat-inactivation varies greatly depending on temperature and duration. Therefore, local validation and verification of heat-inactivation are essential.

category: infectious diseases


title: Multiplexed biosensor for point-of-care COVID-19 monitoring: CRISPR-powered unamplified RNA diagnostics and protein-based therapeutic drug management

abstract: In late 2019 SARS-CoV-2 rapidly spread to become a global pandemic, therefore, measures to attenuate chains of infection, such as high-throughput screenings and isolation of carriers were taken. Prerequisite for a reasonable and democratic implementation of such measures, however, is the availability of sufficient testing opportunities (beyond reverse transcription PCR, the current gold standard). We, therefore, propose an electrochemical, microfluidic multiplexed biosensor in combination with CRISPR/Cas-powered assays for point-of-care nucleic acid testing. In this study, we simultaneously screen for and identify SARS-CoV-2 infections (Omicron-variant) in clinical specimens (Sample-to-result time: [~]30 min), employing LbuCas13a, whilst bypassing reverse transcription as well as target amplification of the viral RNA, both of which are necessary for detection via PCR and multiple other methods. In addition, we demonstrate the feasibility of combining assays based on different classes of biomolecules, in this case protein-based antibiotic detection, on the same device. The programmability of the effector and multiplexing capacity (up to six analytes) of our platform, in combination with a miniaturized measurement setup, including a credit card sized near field communication (NFC) potentiostat and a microperistaltic pump, provide a promising on-site tool for identifying individuals infected with variants of concern and monitoring their disease progression alongside other potential biomarkers or medication clearance.


title: Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition

abstract:
HIV infection has been identified as one of the major risk factors for severe COVID-19 disease, but the mechanisms underpinning this susceptability are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following PBMC stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4+ and CD8+ T cell responses against the Spike protein compared to the viremic PLWH. Absolute CD4 count correlated positively with SARS-CoV-2 specific CD4+ and CD8+ T cell responses (CD4 r= 0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4+ T cell responses (CD4 r= -0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern.

One sentence summaryUnsuppressed HIV infection is associated with muted SARS-CoV-2 T cell responses and poorer recognition of the Beta variant.


title: Immunogenicity of BNT162b2 COVID-19 vaccine in New Zealand adults

abstract:
BackgroundThere is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease.

MethodsThis prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for M[a]ori, Pacific peoples, older adults [≥] 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.1 strains using a surrogate viral neutralisation assay.

Results285 adults with median age of 52 years were included. 55% were female, 30% were M[a]ori, 28% were Pacific peoples, and 26% were [≥]65 years of age. Obesity, cardiac and pulmonary disease and diabetes were more common than in the general population. All participants received 2 doses of BNT162b2 vaccine. At 28 days after second vaccination, 99.6% seroconverted to the vaccine, and anti-S IgG and neutralising antibody levels were high across gender and ethnic groups. IgG and neutralising responses declined with age. Lower responses were associated with age [≥]75 and diabetes, but not BMI. The ability to neutralise the Omicron BA.1 variant in vitro was severely diminished but maintained against other variants of concern.

ConclusionsVaccine antibody responses to BNT162b2 were generally robust and consistent with international data in this COVID-19 naive cohort with representation of key populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability of responses and cellular immune responses should be assessed with attention to elderly adults and diabetics.


title: SARS-CoV-2 Omicron sublineage BA.2 replaces BA.1.1: genomic surveillance in Japan from September 2021 to March 2022

abstract:
ObjectiveThe new emerging Omicron strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading worldwide. We aimed to analyze the genomic evolution of the shifting Omicron virus subtypes.

MethodsThe study included 1,297 individuals diagnosed as SARS-CoV-2 positive by PCR test or antigen quantification test from September 2021 to March 2022. Samples were analyzed by whole genome sequencing analysis (n=489) or TaqMan assay (n=808).

ResultsAfter the outbreak of the SARS-CoV-2 Delta strain, the Omicron strain spread rapidly in Yamanashi, Japan. BA.1.1 was the predominant sublineage of the Omicron strain from January to mid-February 2022, but the number of cases of sublineage BA.2 began to increase after mid-February, and this sublineage was shown to have replaced BA.1.1 by the end of March 2022. We observed higher viral and antigen levels of sublineage BA.2 than of sublineage BA.1.1 in nasopharyngeal swab samples. However, no difference in viral load by patient age was apparent between sublineages BA.1.1 and BA.2.

ConclusionsA transition from sublineage BA.1.1 to sublineage BA.2 was clearly observed over approximately one month. Omicron sublineage BA.2 was found to be more transmissible owing to its higher viral load regardless of patient age.


title: A comparison of regression discontinuity and propensity score matching to estimate the causal effects of statins using electronic health records

abstract: The authors have withdrawn this manuscript because the results are currently in the process of being updated. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

category: epidemiology


title: Altered brain network topology in children with Auditory Processing Disorder: a resting-state multi-echo fMRI study

abstract: Children with auditory processing disorder (APD) experience hearing difficulties, particularly in the presence of competing sounds, despite having normal audiograms. There is considerable debate on whether APD symptoms originate from bottom-up (e.g., auditory sensory processing) and/or top-down processing (e.g., cognitive, language, memory). A related issue is that little is known about whether functional brain network topology is altered in APD. Therefore, we used resting-state functional magnetic resonance imaging data to investigate the functional brain network organization of 57 children from 8 to 13 years old, diagnosed with APD (n=28) and without hearing difficulties (healthy control, HC; n=29). We applied complex network analysis using graph theory to assess the whole-brain integration and segregation of functional networks and brain hub architecture. Our results showed children with APD and HC have similar global network properties -i.e., an average of all brain regions- and modular organization. Still, the APD group showed different hub architecture in default mode-ventral attention, somatomotor and frontoparietal-dorsal attention modules. At the nodal level -i.e., single-brain regions-, we observed decreased participation coefficient (PC - a measure quantifying the diversity of between-network connectivity) in auditory cortical regions in APD, including bilateral superior temporal gyrus and left middle temporal gyrus. Beyond auditory regions, PC was also decreased in APD in bilateral posterior temporo-occipital cortices, left intraparietal sulcus, and right posterior insular cortex. Correlation analysis suggested a positive association between PC in the left parahippocampal gyrus and the listening-in-spatialized-noise - sentences task where APD children were engaged in auditory perception. In conclusion, our findings provide evidence of altered brain network organization in children with APD, specific to auditory networks, and shed new light on the neural systems underlying childrens listening difficulties.


title: Sustained Minimal Residual Disease Negativity in Multiple Myeloma is Associated with Stool Butyrate and Healthier Plant-Based Diets

abstract:
Sustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma (MM). The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We examined the relationship of dietary factors, stool metabolites, and microbial diversity with sustained MRD negativity in patients on lenalidomide maintenance. At 3 months, higher stool butyrate concentration (p=0.037), butyrate producers (p=0.025) and -diversity (p=0.0035) were associated with sustained MRD-negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (p=0.009) and sustained MRD-negativity (p=0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins p=0.01, flavones p=0.01, and flavanols p=0.02). This is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production and sustained MRD-negativity in MM; providing rationale to evaluate a prospective dietary intervention.

Statement of SignificanceWe demonstrate an association between diet, the gut microbiome, and sustained MRD-negativity in MM. A healthy diet, with adequate plant and seafood protein, and containing flavonoids, associates with stool diversity, butyrate production and sustained MRD-negativity. These findings suggest dietary modification should be studied to enhance myeloma control.

Key PointsO_LIIn MM on lenalidomide maintenance, stool butyrate concentration at 3 months was associated with higher rates of MRD negativity at 12 months.
C_LIO_LIIncreased seafood and plant proteins, dietary flavonoids, and diversity of dietary flavonoids correlated with stool butyrate concentrations.
C_LI


title: Loss of CHGA protein as a potential biomarker for colon cancer diagnosis: a study on biomarker discovery by machine learning and confirmation by immunohistochemistry in colorectal cancer tissue microarrays

abstract:
BackgroundIncidences of colon and rectal cancers have been parallelly and constantly increased, however, the mortality has been slightly decreased due to early diagnosis and better therapies during the last decades. Precise early diagnosis for colorectal cancer has been a great challenge in order to win chances for the best choices of cancer therapies.

Patients and methodsWe have started with searching protein biomarkers based on our colorectal biomarker database (CBD), finding differential expressed genes (GEGs) and non-DEGs from RNA sequencing (RNA-seq) data, and further predicted new biomarkers on protein-protein interaction (PPI) networks by machine learning (ML) methods. The best-selected biomarker was further verified by receiver operating characteristic (ROC) test from microarray and RNA-seq data, biological network and functional analysis, and immunohistochemistry in the tissue arrays from 198 specimens.

ResultsThere were twelve proteins (MYO5A, CHGA, MAPK13, VDAC1, CCNA2, YWHAZ, CDK5, GNB3, CAMK2G, MAPK10, SDC2, and ADCY5) which were predicted by ML as colon cancer candidate diagnosis biomarkers. These predicted biomarkers showed close relationships with reported biomarkers on PPI network and shared some pathways. ROC test showed CHGA protein with the best diagnostic accuracy (AUC=0.9 in microarray data and 0.995 in RNA-seq data) among these candidate protein biomarkers. Furthermore, CHGA performed well in the immunohistochemistry test.

ConclusionsProtein expression of CHGA in the normal colorectal mucosa was lost in the colorectal cancers and the lose of CHGA protein might be a potential candidate biomarker for colon or even colorectal cancer diagnosis.

TopicCHGA expression, colon cancer diagnosis

Key MessageThe results of this study suggest that lose of CHGA expression from the normal colon and adjacent mucosa to colon cancer may be used as a valuable biomarker for early diagnosis of colon adenocarcinoma


title: Impulse dispersion of aerosols during playing the recorder and evaluation of safety measures

abstract:
IntroductionGroup musical activities using wind instruments have been restricted during the CoVID19 pandemic due to suspected higher risk of virus transmission. It was presumed that the aerosols exhaled through the tubes while playing would be ejected over larger distances and spread into the room due to jet stream effects. In particular, the soprano recorder is widely used as instrument in school classes and for beginners of all age groups in their musical education, as well as in contexts of leisure activities and in professional concert performances.

Understanding the aerosol impulse dispersion characteristics of playing the soprano recorder could assist with the establishment of concepts for safe music-making.

MethodsFive adult professionally trained soprano recorder players (4 female, 1 male) played four bars of the main theme of L. van Beethovens "Ode to Joy" in low and in high octaves, as well as with 3 different potential protection devices in the high octave. For comparison they spoke the corresponding text by F. Schiller. Before each task, they inhaled .5 L of vapor from an e-cigarette filled with base liquid. The vapor cloud escaping during speaking or playing was recorded by cameras and its spread was measured as a function of time in the three spatial dimensions. The potential safety devices were rated in practicability with a questionnaire, and their influence on the sound was compared, generating a long-term average spectrum from the audio data.

ResultsWhen playing in the high octave, at the end of the task the clouds showed a median distance of 1.06 m to the front and .57 m diameter laterally (maxima: x: 1.35 m and y: .97 m). It was found that the clouds expansion values in playing the recorder with and without safety measures are mostly lower when compared to the ordinary, raised speaking voice of the same subjects.

The safety devices which covered the instrument did not show clear advantages and were rated as unpractical by the subjects. The most effective reduction of the cloud was reached when playing into a suction funnel.

ConclusionThe aerosol dispersion characteristics of soprano recorders seem comparable to clarinets. The tested safety devices which covered holes of the instrument did not show clear benefits.

category: otolaryngology


title: Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy and periventricular calcifications

abstract: PPFIBP1 encodes for the liprin-{beta}1 protein which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 14 individuals from 10 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy and progressive microcephaly. Further common clinical findings included muscular hypertonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired hearing and vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM-domain region that is essential for protein-protein interaction. For further insight in the effects of PPFIBP1 loss-of-function, we performed automated behavioural phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model which revealed defects in spontaneous and light-induced behaviour and confirmed resistance to the acetylcholinesterase inhibitor aldicarb suggesting a defect in the neuronal presynaptic zone. In conclusion, we present bi-allelic loss-of-function variants in PPFIBP1 as a novel cause of an autosomal recessive neurodevelopmental disorder.

category: genetic and genomic medicine


title: Antibody responses to SARS-CoV-2 vaccination in patients with acute leukaemia and high risk MDS on active anti-cancer therapies

abstract: Patients with haematological malignancies, such as acute leukaemia and high-risk MDS (HR-MDS), have significantly increased mortality and morbidity from COVID-19. However vaccine efficacy in these patients and the impact of systemic anti-cancer therapy (SACT) on vaccine response remains to be fully established. SARS-CoV-2 antibody responses in 53 patients with ALL, AML or HR-MDS receiving SACT were characterised following two doses of either BNT162b2 or ChAdOx1nCoV-19. All patients were tested for anti-S antibodies after 2 doses, 60% after the first dose and anti-N antibody testing was performed on 46 patients (87%). Seropositivity rates after 2 vaccine doses were 95% in AML/HR-MDS patients and 79% in ALL. After stratification by prior SARS-CoV-2 infection, naive patients with AML/HR-MDS had higher seroconversion rates and median anti-S antibody titres compared to ALL (median 291U/mL versus 5.06U/mL), and significant increases in anti-S titres with consecutive vaccine doses, not seen in ALL. No difference was seen in serological response between patients receiving intensive chemotherapy or non-intensive therapies (HMA) but significantly reduced titres were present in AML/HR-MDS patients who received venetoclax-based regimens compared to other therapies. All ALL patients received intensive chemotherapy, with no further impact of anti-CD20 immunotherapy on serological response. Understanding the impact of disease subtypes and therapy on vaccine response is essential to enable decisions on modifying or delaying treatment in the context of either SARS-CoV-2 infection or vaccination.


title: High incidence of sotrovimab resistance and viral persistence after treatment of immunocompromised patients infected with the SARS-CoV-2 Omicron variant

abstract:
BackgroundSotrovimab is a monoclonal antibody that neutralizes SARS-CoV-2 by binding to a highly conserved epitope in the receptor binding domain. It retains activity against the Omicron BA.1 variant and is used to treat immunocompromised patients as they are at increased risk for a severe outcome of COVID-19.

MethodsWe studied viral evolution in 47 immunocompromised patients infected with Omicron BA.1 or 2 and treated with sotrovimab. SARS-CoV-2 PCR was performed at baseline and weekly thereafter until Ct-value was [≥] 30. All RNA samples were sequenced to determine the variant and occurrence of mutations, in particular in the Spike protein, after treatment.

ResultsTwenty-four (51%) of the 47 patients were male and their median age was 63 years. Thirty-one (66%) had undergone a solid organ transplantation and 13 (28%) had received prior B-cell depleting therapy. Despite a history of vaccination, 24 of 30 patients with available data on anti-SARS-CoV-2 IgG Spike antibodies prior to treatment with sotrovimab had very low or no antibodies. Median time to viral clearance (Ct-value [≥] 30) after treatment was 15 days (IQR 7-22). However, viral RNA with low Ct-values was continuously detected for at least 28 days after treatment in four patients infected with BA.1. Mutations in the Spike protein at position 337 or 340 were observed in all four patients. Similar mutations were also found after treatment of two patients with a BA.2 infection but both cleared the virus within two weeks. Thus following treatment with sotrovimab, spike mutations associated with reduced in vitro susceptibility were detected in 6 of 47 (13%) patients.

ConclusionViral evolution towards resistance against sotrovimab can explain treatment failure in most immunocompromised patients and these patients can remain infectious after treatment. Therefore, documenting viral clearance after treatment is recommended to avoid that these patients unintentionally become a source of new, sotrovimab resistant, variants. Research on direct acting antivirals and possibly combination therapy for the treatment of COVID-19 in immunocompromised patients is needed.


title: Predictors for Reactogenicity and Humoral Immunity to SARS-CoV-2 Following Infection and mRNA Vaccination: A Regularized Mixed-Effects Modelling Approach

abstract:
BackgroundThe influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood.

MethodsTen-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses in COVID+ participants in a longitudinal cohort study.

ResultsIn previously infected individuals, AB were more durable and robust following vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination, as were the demographic factors of age and Hispanic ethnicity. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination.

ConclusionVaccination in COVID+ individuals ensures a more robust immune response. Experiencing systemic and local symptoms post-vaccine is suggestive of higher AB, which may confer greater protection. Age and Hispanic ethnicity are predictive of higher AB.


title: Monitoring of SARS-CoV-2 variant dynamics in wastewater by digital RT-PCR : from Alpha to Omicron BA.2 VOC

abstract: Throughout the COVID-19 pandemic, new variants have continuously emerged and spread in populations. Among these, variants of concern (VOC) have been the main culprits of successive epidemic waves, due to their transmissibility, pathogenicity or ability to escape the immune response. Quantification of the SARS-CoV-2 genomes in raw wastewater is a reliable approach well-described and widely deployed worldwide to monitor the spread of SARS-CoV-2 in human populations connected to sewage systems. Discrimination of VOCs in wastewater is also a major issue and can be achieved by genome sequencing or by detection of specific mutations suggesting the presence of VOCs. This study aimed to date the emergence of these VOCs (from Alpha to Omicron BA.2) by monitoring wastewater from the greater Paris area, France, but also to model the propagation dynamics of these VOCs and to characterize the replacement kinetics of the majority populations. These dynamics were compared to various individual-centered public health data, such as regional incidence and proportions of VOCs identified by sequencing of isolated patient strains. The viral dynamics in wastewater highlighted the impact of the vaccination strategy on the viral circulation in human populations but also suggested its potential effect on the selection of variants most likely to be propagated in immunized populations. Normalization of concentrations to capture population movements appeared statistically more reliable using variations in local drinking water consumption rather than using PMMoV concentrations because PMMoV fecal shedding was subject to variability and was not sufficiently relevant in this study. The dynamics of viral spread was observed earlier (about 13 days on the wave related to Omicron VOC) in raw wastewater than the regional incidence alerting to a possible risk of decorrelation between incidence and actual virus circulation probably resulting from a lower severity of infection in vaccinated populations.


title: Analysis of immunization, adverse events, and efficacy of a fourth dose of BNT162b2 vaccine

abstract:
ImportanceScarce information exists concerning the seroconversion and adverse events after immunization (AEFI) of the fourth dose of a SARS-COV-2 vaccine.

ObjectiveCorrelate the magnitude of the antibody response to vaccination with previous clinical conditions and AEFI of the fourth dose of BNT162b2 mRNA.

DesignObservational study where SARS-CoV-2 spike 1-2 IgG antibodies IgG titers were measured 21-28 days after the exposition of the first, and second dose, three months after the second dose, 1-7 days after the third dose, before the fourth dose, and 21-28 days after the fourth dose of BNT162b2 mRNA.

SettingThe study was conducted on healthcare workers of a private hospital in Northern Mexico.

ParticipantsInclusion criteria were healthcare workers of both genders, any age, who planned to conclude the immunization regimen. The exclusion criteria were previously given any SARS-CoV-2 vaccine prior to study entry.

InterventionSubjects were exposed to four doses of the BNT162b2 mRNA vaccine.

Main Outcome and Measures:

The anti-S1 and anti-S2 IgG antibodies against SARS-CoV-2 in plasma samples were measured with chemiluminescence immunoassay developed by DiaSorin.

ResultsWe recruited 112 subjects [43 (SD 9) years old, 74% women].

After the first dose, subjects had a median (IQR) AU/ml IgG of 122(1904), with an increase to 1875 (2095) after the second dose, 3020 (2330) after the third dose, and 4230 (3393) after 21-28 of a fourth dose (p<0.01). The number (%) of any AEFI between doses was 90 (80.4), 89(79), 65(58), 69 (61.5), after first, second, third, and fourth, respectively, p<0.001. After the fourth dose, the most frequent AEFI was pain at the injection site (87%). Fever was slightly more frequent after the third and fourth doses, 9 (13.8) and 8 (11.4%) cases, respectively, and adenopathy was more frequent after the fourth dose [in11(15.7%) cases]. There was a correlation between AEFI in the fourth dose with gender and antibody levels (p<0.05). The highest proportion of AEFI was considered mild after the fourth dose. During the Omicron outbreak, 6 (5.3%) had mild SARS-CoV-2 during 8-28 days of the fourth dose.

Conclusions and RelevanceThe fourth dose of BNT162b2mRNA increases S1/S2 IgG 33.6 times with mild adverse events.

Registration numberNCT05228912

Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the magnitude of antibody response to vaccination and adverse events after immunization (AEFI) of a fourth dose of BNT162b2 mRNA?

FindingsThis cohort included 112 healthcare workers. We measured S1/S2 IgG vs. SARS-CoV-2 after the first, second, third and fourth dose. Compared to the first dose, antibodies increased 33.6 times the antibody levels after the fourth dose. We found minimal to moderate adverse events. The change in antibodies correlated with AEFI. During the Omicron outbreak 6 (5.3%) had mild SARS-CoV-2.

MeaningA fourth dose of BNT162b2mRNA increases S1/S2 IgG with mild to moderate adverse events.


title: Human Papillomavirus Infection Rate by Genotype and Vaccination Rates in Canada: Canadian Health Measures Survey 2009 to 2013

abstract:
BackgroundAn infection with certain HPV genotypes can lead to cancer or genital warts. HPV can be detected with PCR-based tests, and some genotypes can be prevented by vaccines. However, since the infection rates of various HPV genotypes have not been well reported, the present study aims to provide this information.

MethodsThe Canadian Health Measures Survey (CHMS) is an ongoing biannual national survey. Between 2009 and 2011, it sampled a nationally representative sample of females aged 14 to 59 years to determine the infection rates of 46 HPV genotypes. Females aged 9 to 29 years and 9 to 59 years were asked whether they received HPV vaccines between 2009 to 2011 (cycle 2) and 2012 to 2013 (cycle 3), respectively. The reported infection rates and vaccination proportions were weighted and adjusted for the survey design.

ResultsAmong the estimated 10,592,968 females aged 14 to 59 years at cycle 2, the HPV genotypes with the highest infection rates were 16, 62, 74, and 54, and the rates were 3.42% (95% CI = 1.67% to 5.17%), 2.14% (95% CI = 0.68% to 3.59%), 2.1% (95% CI = 0.51% to 3.69%), and 2.04% (95% CI = 0.38% to 3.7%), respectively. There were an estimated 6,569,100 and 11,603,752 females aged 9 to 29 and 9 to 59 years at cycles 2 and 3, respectively. The proportions receiving a HPV vaccine were 13.55% (11.18% to 15.92%) and 12.3% (9.8% to 14.79%), respectively. The estimated numbers of females that received HPV vaccines were 890,197 and 1,427,000, respectively.

ConclusionCanada is one of the few countries that conduct national surveys to determine HPV infection rates by genotype, which are not limited to the surveillance of carcinogenic genotypes. Our study found discrepancies between the HPV genotypes whose infections were the most common, that could be detected by PCR tests, that were carcinogenic, and that could be prevented by vaccines. For example, 5 of the 7 genotypes (42, 54, 62, 66, and 74) with infection rates of more than 1% cannot be detected by PCR tests and are not targeted by vaccines. HPV 51 is carcinogenic, associated with genital warts, and can be detected by PCR tests, but it is not targeted by vaccines. We recommend a better alignment of the genotypes targeted by HPV tests and vaccines with those genotypes with the highest infection rates in Canada.


title: Prophylactic and reactive vaccination strategies for healthcare workers against MERS-CoV

abstract: Several vaccines candidates are in development against Middle East respiratory syndrome-related coronavirus (MERS-CoV), which remains a major public health concern. Using individual-level data on the 2013-2014 Kingdom of Saudi Arabia epidemic, we employ counterfactual analysis on inferred transmission trees ("who-infected-whom") to assess potential vaccine impact. We investigate the conditions under which prophylactic "proactive" campaigns would outperform "reactive" campaigns (i.e. vaccinating either before or in response to the next outbreak), focussing on healthcare workers. Spatial scale is crucial: if vaccinating healthcare workers in response to outbreaks at their hospital only, proactive campaigns perform better, unless efficacy has waned significantly. However, campaigns that react at regional or national level consistently outperform proactive campaigns. Measures targeting the animal reservoir reduce transmission linearly, albeit with wide uncertainty. Substantial reduction of MERS-CoV morbidity and mortality is possible when vaccinating healthcare workers, underlining the need for at-risk countries to stockpile vaccines when available.


title: Prepandemic prevalence estimates of fatty liver disease and fibrosis defined by liver elastography in the United States

abstract:
Background & AimsFatty liver disease is a growing public health burden with serious consequences. We estimated prepandemic prevalence of fatty liver disease determined by transient elastography assessed hepatic steatosis and fibrosis, and examined associations with lifestyle and other factors in a United States population sample.

MethodsLiver stiffness and controlled attenuation parameter (CAP) were assessed on 7,923 non-Hispanic white, non-Hispanic black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 prepandemic data.

ResultsThe prevalence of fatty liver disease estimated by CAP >300 dB/m was 28.8% and of fibrosis (liver stiffness >8 kPa) was 10.4%. Only 7.2% of participants with fatty liver disease and 10.9% with fibrosis reported being told by a health care provider that they had liver disease. In addition to known risk factors such as metabolic factors and ALT, persons with fatty liver disease were less likely to meet physical activity guidelines, more likely to be sedentary for 12 or more hours a day, and reported a less healthy diet. Persons with fibrosis were less likely to have a college degree and reported a less healthy diet.

ConclusionIn the U.S. population, most persons with fatty liver disease are unaware of their condition. Although physical activity and dietary modifications might reduce the fatty liver disease burden, the COVID pandemic has been less favorable for lifestyle changes. There is an urgent need for fatty liver disease management in high-risk individuals using transient elastography or other noninvasive methods to intervene in disease progression.

category: gastroenterology


title: Serious underlying medical conditions and COVID-19 vaccine hesitancy.

abstract:
ObjectiveTo examine vaccine uptake, hesitancy and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination.

DesignCross-sectional survey.

SettingTen Australian health services.

Participants4683 patients (3560 cancer, 842 diabetes and 281 multiple sclerosis) receiving care at the health services participated in the 42-item survey, between June 30 to October 5, 2021.

Main outcome measuresSociodemographic and disease-related characteristics, COVID-19 vaccine uptake, and the scores of three validated scales which measured vaccine hesitancy and vaccine-related beliefs generally and specific to the participants disease, including the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale. Multivariable logistic regression was used to determine the associations between scale scores and vaccine uptake.

ResultsOf all participants, 81.5% reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas (all p<0.05). Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines (all p<0.05). Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment (all p<0.05).

ConclusionsDisease-specific concerns impact COVID-19 vaccine-related behaviours and beliefs in people with serious and/or chronic health conditions. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.

Trial registrationACTRN12621001467820

category: public and global health


title: Pre-Diagnostic Cognitive and Functional Impairment in Multiple Sporadic Neurodegenerative Diseases

abstract:
INTRODUCTIONThe pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, pre-diagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease.

METHODSUK Biobank data was extracted. Cognitive and functional measures in individuals who subsequently developed Alzheimers Disease, Parkinsons Disease, Frontotemporal Dementia, Progressive Supranuclear Palsy, Dementia with Lewy Bodies, or Multiple System Atrophy, were compared against those without neurodegenerative diagnoses. The same measures were regressed against time to diagnosis, after adjusting for the effects of age.

RESULTSThere was evidence for pre-diagnostic cognitive impairment and decline with time, particularly in Alzheimers. Pre-diagnostic functional impairment and decline was observed in multiple diseases.

DISCUSSIONThe scale and longitudinal follow-up of UK Biobank participants provides evidence for cognitive and functional decline years before symptoms become obvious in multiple neurodegenerative diseases. Identifying pre-diagnostic functional and cognitive changes could improve selection for preventive and early disease-modifying treatment trials.

Research in ContextO_ST_ABSSystematic reviewC_ST_ABSStudies of genetic dementia cohorts provide evidence for pre-diagnostic changes in disease biomarkers and cognitive function in several genetic neurode-generative diseases. The pre-diagnostic phase of sporadic neurodegenerative disease has been less well-studied. It is unclear whether early functional or cognitive changes are detectable in sporadic neurodegenerative disease.

InterpretationWe have established an approach to identify cognitive and functional pre-diagnostic markers of neurodegenerative disease years before diagnosis. We found disease-relevant patterns of pre-diagnostic cognitive and functional impairment, and observed a pre-diagnostic linear decline in a number of cognitive and functional measures.

Future DirectionsOur approach can form the basis for pre-diagnostic cognitive and functional screening to recruit into trials of disease prevention and disease modifying therapies for neurodegenerative diseases. A screening panel based on cognition and function could be followed by disease-specific biomarkers to further improve risk stratification.

category: neurology


title: Pandemic-EBT and grab-and-go school Meals: Costs, reach, and benefits of two approaches to keep children fed during school closures due to COVID-19

abstract:
ImportanceSchool meals improve nutrition and health for millions of U.S. children. School closures due to the COVID-19 pandemic disrupted childrens access to school meals. Two policy approaches were activated to replace missed meals for children from low-income families. The Pandemic Electronic Benefit Transfer (P-EBT) program provided the cash value of missed meals directly to families on debit-like cards to use for making food purchases. The grab-and-go meals program offered prepared meals from school kitchens at community distribution points. The effectiveness of these programs at reaching those who needed them and their costs were unknown.

ObjectiveTo determine how many eligible children were reached by P-EBT and grab-and-go meals, how many meals or benefits were received, and how much each program cost to implement.

DesignCross-sectional study, Spring 2020.

SettingNational.

ParticipantsAll children <19 years old and children age 6-18 eligible to receive free or reduced price meals (FRPM).

Exposure(s)Receipt of P-EBT or grab-and-go school meals.

Main Outcome(s) and Measure(s)Percentage of children reached by P-EBT and grab-and-go school meals; average benefit received per recipient; and average cost, including implementation costs and time costs to families, per meal distributed.

ResultsGrab-and-go school meals reached about 10.5 million children (17% of all US children), most of whom were FRPM-eligible students. Among FRPM-eligible students only, grab-and-go meals reached 27%, compared to 89% reached by P-EBT. Among those receiving benefits, the average monthly benefit was larger for grab-and-go school meals ($148) relative to P-EBT ($110). P-EBT had lower costs per meal delivered - $6.51 - compared to $8.20 for grab- and-go school meals. P-EBT had lower public sector implementation costs but higher uncompensated time costs to families (e.g., preparation time for meals) compared to grab-and-go school meals.

Conclusions and RelevanceBoth programs supported childrens access to food when schools were closed and in complementary ways. P-EBT is an efficient and effective policy option to support food access for eligible children when school is out.

KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat were the operating costs, costs and benefits to families, and proportion of eligible children who received benefits of two programs aimed at replacing school meals missed when schools were closed due to COVID-19?

FindingsIn this cross sectional analysis, we found that the Pandemic-Electronic Benefit Transfer program, in which state agencies sent debit cards loaded with the cash value of missed school meals directly to families, reached nearly all low income students (89%) and cost relatively little per meal provided. In comparison, grab-and-go school meals, in which school food service departments provided prepared meals for offsite consumption, reached 27% of low income children and was associated with larger per meal costs.

MeaningDuring times when children cannot access school meals, state and federal agencies should support cost-efficient programs for schools to distribute prepared meals and activate programs like P-EBT to efficiently reach eligible children.

category: nutrition


title: Delta/ Omicron and Omicron/BA.2 co-infections occurring in Immunocompromised hosts

abstract: Concomitant infection of multiple SARS-CoV-2 variants has become an increasing concern, as this scenario increases the likelihood of recombinant variants. Detecting co-infection of SARS-CoV-2 variants is difficult to detect by whole genome sequencing approaches, but genotyping methods facilitate detection. We describe 2 cases of Delta/Omicron and 2 cases of Omicron sublineage BA.1/ BA.2 co-infection as detected by a multiplex genotyping fragment analysis method. Findings were confirmed by whole genome sequencing. Review of the patient characteristics revealed co-morbidities and conditions which weaken the immune system and may make them more susceptible to harboring SARS-CoV-2 variant co-infections.


title: Racial/Ethnic, Biomedical, and Sociodemographic Risk Factors for COVID-19 Positivity and Hospitalization in the San Francisco Bay Area

abstract:
BACKGROUNDThe COVID-19 pandemic has uncovered clinically meaningful racial/ethnic disparities in COVID-19-related health outcomes. Current understanding of the basis for such an observation remains incomplete, with both biomedical and social/contextual variables proposed as potential factors.

PURPOSEUsing a logistic regression model, we examined the relative contributions of race/ethnicity, biomedical, and socioeconomic factors to COVID-19 test positivity and hospitalization rates in a large academic health care system in the San Francisco Bay Area prior to the advent of vaccination and other pharmaceutical interventions for COVID-19.

RESULTSWhereas socioeconomic factors, particularly those contributing to increased social vulnerability, were associated with test positivity for COVID-19, biomedical factors and disease co-morbidities were the major factors associated with increased risk of COVID-19 hospitalization. Hispanic individuals had a higher rate of COVID-19 positivity, while Asian persons had higher rates of COVID-19 hospitalization. Diabetes was an important risk factor for COVID-19 hospitalization, particularly among Asian patients, for whom diabetes tended to be more frequently undiagnosed and higher in severity.

CONCLUSIONSWe observed that biomedical, racial/ethnic, and socioeconomic factors all contributed in varying but distinct ways to COVID-19 test positivity and hospitalization rates in a large, multiracial, socioeconomically diverse metropolitan area of the United States. The impact of a number of these factors differed according to race/ethnicity. Improving over-all COVID-19 health outcomes and addressing racial and ethnic disparities in COVID-19 out-comes will likely require a comprehensive approach that incorporates strategies that target both individual-specific and group contextual factors.


title: Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1H and 129Xe lung MRI

abstract:
IntroductionMicrovascular abnormalities and impaired 129Xe gas transfer have been observed in patients with COVID-19. The progression of pathophysiological pulmonary changes during the post-acute period in these patients remains unclear.

MethodsPatients who were hospitalised due to COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25 and 50 weeks after hospital admission. The imaging protocol included: ultra-short echo time, dynamic contrast enhanced lung perfusion, 129Xe lung ventilation, 129Xe diffusion weighted and 129Xe 3D spectroscopic imaging of gas exchange.

Results9 patients were recruited and underwent MRI at 6 (n=9), 12 (n=9), 25 (n=6) and 50 (n=3) weeks after hospital admission. At 6 weeks after hospital admission, patients demonstrated impaired 129Xe gas transfer (RBC:M) but normal lung microstructure (ADC, LmD). Minor ventilation abnormalities present in four patients were largely resolved in the 6-25 week period. At 12 week follow up, all patients with lung perfusion data available (n=6) showed an increase in both pulmonary blood volume and flow when compared to 6 weeks, though this was not statistically significant. At 12 and 25 week follow up, significant improvements in 129Xe gas transfer were observed compared to 6-week examinations, however 129Xe gas transfer remained abnormally low.

ConclusionsThis study demonstrates that multinuclear MRI is sensitive to functional pulmonary changes in the follow up of patients who were hospitalised with COVID-19. Persistent impairment of xenon transfer may represent a physiological mechanism underlying ongoing symptoms in some patients and may indicate damage to the pulmonary microcirculation.

category: radiology and imaging


title: CHANGES IN LIFE EXPECTANCY BETWEEN 2019 AND 2021: UNITED STATES AND 19 PEER COUNTRIES

abstract:
BACKGROUNDPrior studies reported large decreases in US life expectancy during 2020 as a result of the COVID-19 pandemic, disproportionately affecting Hispanic and non-Hispanic Black populations and vastly exceeding the average change in life expectancy in other high-income countries. Life expectancy estimates for 2021 have not been reported. This study estimated changes in life expectancy during 2019-2021 in the US population, in three US racial/ethnic groups, and in 19 peer countries.

METHODSUS and peer country death data for 2019-2021 were obtained from the National Center for Health Statistics, the Human Mortality Database, and overseas statistical agencies. The 19 peer countries included Austria, Belgium, Denmark, England and Wales, Finland, France, Germany, Israel, Italy, Netherlands, New Zealand, Northern Ireland, Norway, Portugal, Scotland, South Korea, Spain, Sweden, and Switzerland. Life expectancy was calculated for 2019 and 2020 and estimated for 2021 using a previously validated modeling method.

RESULTSUS life expectancy decreased from 78.86 years in 2019 to 76.99 years in 2020 and 76.47 years in 2021, a net loss of 2.39 years. In contrast, peer countries averaged a smaller decrease in life expectancy between 2019 and 2020 (0.57 years) and a 0.27-year increase between 2020 and 2021, widening the gap in life expectancy between the United States and peer countries to more than five years. The decrease in US life expectancy was highly racialized: whereas the largest decreases in 2020 occurred among Hispanic and non-Hispanic Black populations, in 2021 only the non-Hispanic White population experienced a decrease in life expectancy.

DISCUSSIONThe US mortality experience during 2020 and 2021 was more severe than in peer countries, deepening a US disadvantage in health and survival that has been building for decades. Over the two-year period between 2019 and 2021, US Hispanic and non-Hispanic Black populations experienced the largest losses in life expectancy, reflecting the legacy of systemic racism and inadequacies in the US handling of the pandemic. Reasons for the crossover in racialized outcomes between 2020 and 2021, in which life expectancy decreased only in the non-Hispanic White population, could have multiple explanations.


title: Diabetes Management Beliefs among Adults Diagnosed with Type 2 Diabetes in Iran: A Theory Informed Approach from a Theory of Planned Behavior Framework

abstract:
ObjectiveThe current study was informed by the belief basis of Ajzens (1991) Theory of Planned Behavior (TPB) to identify the important behavioral (advantages and disadvantages), normative (important referents) and control (barriers and facilitators) beliefs associated with the key recommended prevention and management behaviors for adults in Iran diagnosed with Type 2 diabetes (T2D).

MethodsA cross-sectional study was conducted. A total of 115 adults diagnosed with T2D completed a questionnaire examining behavioral, normative and control beliefs and intention in relation to the three diabetes management behaviors including low fat food consumption, carbohydrate counting and physical activity. For each behavior, intention was considered as dependent variable; beliefs were independent variables. Analyses involved three multivariate one-way analysis of variance (MANOVAs).

ResultsThe findings for carbohydrate counting and physical activity suggested behavioral and control beliefs as differentiating high from low intenders to perform the behavior. For carbohydrate counting, behavioral beliefs such as weight control, improving ones health, feeling good and controlling diabetic complications differed significantly between low and high intenders. For physical activity, feeling good, controlling blood sugar and tiredness were among behavioral beliefs differentiating low and high intenders. Medical advice from professionals and greater knowledge were identified as facilitators of carbohydrate counting. High costs were identified as a key barrier preventing individuals from engaging in physical activity. Spouse was the single significant referent influencing carbohydrate counting.

Conclusions & ImplicationsIdentifying the underlying beliefs of key diabetes management behaviors can assist in the design of tailored educational interventions for individuals with T2D.

category: primary care research


title: Have deaths of despair risen during the COVID-19 pandemic? A rapid systematic review

abstract:
ObjectiveTo systematically review the literature on the impact of the COVID-19 pandemic on deaths of despair (suicide, overdoses and drug-related liver diseases).

MethodsFive electronic databases were searched using search terms on deaths of despair and COVID-19.

ResultsThe review of 70 publications included indicates that there is no change or a decline in the suicide rate during the pandemic compared to the pre-pandemic period. Drug-related deaths such as overdose deaths and liver diseases, however, have been increased compared to the pre-pandemic rate. Findings are mainly from middle-high- and high-income countries and data from low-income countries are lacking. Synthesis of data from subgroup analysis indicates that some groups such as Black people, women and younger age groups would be more vulnerable to socioeconomic disruption during the pandemic.

ConclusionStudies included in this review were preliminary and suffered from methodological limitations such as lack of inferential analysis or using provisional data. Further high-quality studies are needed considering the contribution of factors such as disease prevalence, government intervention and environmental characteristics.


title: Does pre-infection stress increase the risk of long COVID? Longitudinal associations between adversity worries and experiences in the month prior to COVID-19 infection and the development of long COVID and specific long COVID symptoms

abstract:
BackgroundLong COVID is increasingly recognised as public health burden. Demographic and infection-related characteristics have been identified as risk factors, but less research has focused on psychosocial predictors such as stress immediately preceding the index infection. Research on whether stressors predict the development of specific long COVID symptoms is also lacking.

MethodsData from 1,966 UK adults who had previously been infected with COVID-19 and who took part in the UCL COVID-19 Social Study were analysed. The number of adversity experiences (e.g., job loss) and the number of worries about adversity experiences within the month prior to COVID-19 infection were used to predict the development of self-reported long COVID and the presence of three specific long COVID symptoms (difficulty with mobility, cognition, and self-care). The interaction between a three-level index of socio-economic position (SEP; with higher values indicating lower SEP) and the exposure variables in relation to long COVID status was also examined. Analyses controlled for a range of COVID-19 infection characteristics, socio-demographics, and health-related factors.

FindingsOdds of self-reported long COVID increased by 1.25 (95% confidence interval [CI]: 1.04 to 1.51) for each additional worry about adversity in the month prior to COVID-19 infection. Although there was no evidence for an interaction between SEP and either exposure variable, individuals in the lowest SEP group were nearly twice as likely to have developed long COVID as those in the highest SEP group (OR: 1.95; 95% CI: 1.19 to 3.19) and worries about adversity experiences remained a predictor of long COVID (OR: 1.43; 95% CI: 1.04 to 1.98). The number of worries about adversity experiences also corresponded with increased odds of certain long COVID symptoms such as difficulty with cognition (e.g., difficulty remembering or concentrating) by 1.46 (95% CI: 1.02 to 2.09) but not with mobility (e.g., walking or climbing steps) or self-care (e.g., washing all over or dressing).

InterpretationResults suggest a key role of stress in the time preceding the acute COVID-19 infection for the development of long COVID and for difficulty with cognition specifically. These findings point to the importance of mitigating worries and experiences of adversities during pandemics both to reduce their psychological impact but also help reduce the societal burden of longer-term illness.

FundingThe Nuffield Foundation [WEL/FR-000022583], the MARCH Mental Health Network funded by the Cross-Disciplinary Mental Health Network Plus initiative supported by UK Research and Innovation [ES/S002588/1], and the Wellcome Trust [221400/Z/20/Z and 205407/Z/16/Z].


title: Clinical Impact of IDH1 Mutations and MGMT Methylation in Adult Glioblastoma Multiforme

abstract:
BackgroundGenetic aberrations and epigenetic alterations have been reported in different types of cancer. Impact of Isocitrate dehydrogenase1 (IDH1) and O6-methylguanine-DNAmethyltransferase (MGMT) in glioblastoma multiforme (GBM) have been of great interest due to their implications in prediction of prognosis of several types of cancer. Authors aimed to investigate the clinical role of IDH1 mutation and MGMT methylation pattern among GBM patients versus non-neurooncological diseases (NND) patients and their impact on survival criteria.

MethodsFormalin-Fixed Paraffin-Embedded (FFPE) tissue sections of 58 GBM and 20 non-onconeurological diseases patients were recruited and IDH1 mutation were detected using Cast-PCR technology and MGMT methylation was detected using Methyl II quantitative PCR approach. Their results were assessed with other clinicopathological criteria and assess its correlation with survival patterns.

ResultsIDH1 mutation was detected among 15 GBM cases (15/58) and it was not reported among NND (P=0.011). Receiver operating characteristic (ROC) curve were plotted to discriminate between MGMT methylation among studied groups. Patients with MGMT methylation [≥] 66% was reported as high methylation, which was recorded significantly in 51.7% and 100% of GBM cases and NND, respectively. Both showed significant difference with performance status, while MGMT methylation was significantly related with tumor size and tumor location. IDH1 mutation and MGMT methylation reported significant increase with GBM patients revealed complete response to treatment. Survival pattern was better for IDH1 mutation and MGMT high methylation as compared to IDH1 wild type or MGMT low-moderate methylation, respectively and favorable survival was detected when both were combined than using either of them alone.

ConclusionDetection of IDH1 mutation and MGMT methylation among GBM patients could aid in prediction of their response to treatment and their survival patterns, and their combination is better than using any of them alone.


title: Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders

abstract: World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have higher prevalence (23%) of persistent, clinically significant WTC-related post-traumatic stress disorder (WTC-PTSD). Here, we applied eigenvector centrality (EC) metrics and data driven methods on resting state functional magnetic resonance (fMRI) outcomes to investigate neural mechanisms underlying WTC-PTSD and to identify how EC shifts in brain areas relate to WTC-exposure and behavioral symptoms. Nine brain areas differed significantly and contributed the most to differentiate functional neuro-profiles between WTC-PTSD and non-PTSD responders. The association between WTC-exposure and EC values differed significantly between WTC-PTSD and non-PTSD in the right anterior parahippocampal gyrus and left amygdala (p= 0.010; p= 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, the index of PTSD symptoms was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Our understanding of functional changes in neural mechanisms underlying WTC-related PTSD is key to advance intervention and treatment.


title: Summaries, Analysis and Simulations of Recent COVID-19 Epidemics in Mainland China

abstract:
BackgroundGlobally COVID-19 epidemics have caused tremendous disasters. China prevented effectively the spread of COVID-19 epidemics before 2022. Recently Omicron and Delta variants cause a surge in reported COVID-19 infections.

MethodsUsing differential equations and real word data, this study modelings and simulates COVID-19 epidemic in mainland China, estimates transmission rates, recovery rates, and blocking rates to symptomatic and asymptomatic infections. The transmission rates and recovery rates of the foreign input COVID-19 infected individuals in mainland China have also been studied.

ResultsThe simulation results were in good agreement with the real word data. The recovery rates of the foreign input symptomatic and asymptomatic infected individuals are much higher than those of the mainland COVID-19 infected individuals. The blocking rates to symptomatic and asymptomatic mainland infections are lower than those of the previous epidemics in mainland China. The blocking rate implemented between March 24-31, 2022 may not prevent the rapid spreads of COVID-19 epidemics in mainland China. For the foreign input COVID-19 epidemics, the numbers of the current symptomatic individuals and the asymptomatic individuals charged in medical observations have decreased significantly after March 17 2022.

ConclusionsNeed to implement more strict prevention and control strategies to prevent the spread of the COVID-19 epidemics in mainland China. Keeping the present prevention and therapy measures to foreign input COVID-19 infections can rapidly reduce the number of foreign input infected individuals to a very low level.


title: Genetic Risk for Attention-Deficit/Hyperactivity Disorder Predicts Cognitive Decline and Development of Alzheimer's Disease Pathophysiology in Cognitively Unimpaired Older Adults

abstract:
BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) persists in older age and is postulated to be a risk factor for cognitive impairment and Alzheimers Disease (AD). However, this notion relies exclusively on epidemiological associations, and no previous study has linked ADHD with a decline in cognitive performance in older adults or with AD progression. Therefore, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with longitudinal cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults.

MethodsWe calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years) using whole-genome information. These individuals had baseline amyloid-{beta} (A{beta}) positron emission tomography, as well as longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181, structural magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers.

OutcomesHigher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain A{beta} deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau181 levels and frontoparietal atrophy in CU A{beta}-positive individuals.

InterpretationOur results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology in the CU elderly. These findings indicate that ADHD-PRS might inform the risk of developing cognitive decline in this population.

FundingNational Institute of Health and Brain & Behavioral Research Foundation.

category: psychiatry and clinical psychology


title: INTERCEPT pathogen reduction of platelet concentrates induces trans-arachidonic acids and affects eicosanoid formation

abstract:
Gamma-irradiation of blood products is mandatory to avoid graft versus host disease in patients with immunosuppressed clinical conditions. Pathogen inactivation techniques were implemented to optimize safe blood component supply. The INTERCEPT treatment uses amotosalen together with UVA irradiation. The functional and molecular implications of these essential treatments have not yet been systematically assessed. The irradiation-induced inactivation of nucleic acids may actually be accompanied with modifications of chemically reactive polyunsaturated fatty acids, known to be important mediators of platelet functions. Thus, here we investigated eicosanoids and related fatty acids released upon treatment and during platelet storage for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. In contrast to gamma-irradiation, here we demonstrate that UVA treatment attenuated the formation of ALOX12-products such as 12-HETE and 12-HEPE but induced the formation of trans-arachidonic acids in addition to 11-HETE and HpODEs. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation and clot firmness hardly differed between the two treatment groups. In vitro synthesis of trans-arachidonic acids (trans-AA) out of arachidonic acid in the presence of {beta}-mercaptoethanol suggested that thiol radicals formed by UVA treatment are responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is plausible to assume that trans-AA and other UVA-induced molecules may have specific biological effects on the recipients, which need to be addressed in future studies.

Key pointsO_LIA previously unrecognized radical mechanisms for the generation of trans-fatty acids by UVA was identified
C_LIO_LIIrradiation with UVA was found to immediately affect the generation of polyunsaturated fatty acid oxidation products
C_LI

category: intensive care and critical care medicine


title: STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study Protocol.

abstract:
IntroductionAs mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs.

Methods and analysisThis study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID.

Ethics and disseminationEthical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID.

RegistrationResearchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.

Strengths and limitations of this studyO_ST_ABSGapC_ST_ABSThere is no general model for providing ICPs to many LTCs, especially in case of multi-morbidity or MNYES.

SolutionWe will develop policy recommendations for such ICPs based upon a Delphi process exploring the value and interchangeability of elements of ICPs for Long COVID. This will help patients and clinicians navigate access to, or provide ICPs for, LTCs.

StrengthsA key tenet is that people with lived experience of Long COVID or an LTC will be involved from inception in the design and conduct of the study.

WeaknessesPossible under-representation of digitally hard to reach groups, although efforts will be made to ensure that data collection is widely inclusive, following the NIHR INCLUDE framework.

category: health systems and quality improvement


title: Use of face masks did not impact COVID-19 incidence among 10-12-year-olds in Finland

abstract: In fall 2021 in Finland, the recommendation to use face masks in schools for pupils ages 12 years and above was in place nationwide. Some cities recommended face masks for younger pupils as well. Our aim was to compare COVID-19 incidence among 10-12-year-olds between cities with different recommendations on the use of face masks in schools. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, where clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner, including information such as date of birth, gender, and place of residence. The NIDR is linked to the population data registry, enabling calculation of incidences. We compared the differences in trends of 14-day incidences between Helsinki and Turku among 10-12-year-olds, and for comparison, also among ages 7-9 and 30-49 by using joinpoint regression. According to our analysis, no additional effect seemed to be gained from this, based on comparisons between the cities and between the age groups of the unvaccinated children (10-12 years versus 7-9 years).


title: Prediction of deterioration from COVID-19 in patients in skilled nursing facilities using wearable and contact-free devices: a feasibility study

abstract:
Background and RationaleApproximately 35% of all COVID-19 deaths occurred in Skilled Nursing Facilities (SNFs). In a healthy general population, wearables have shown promise in providing early alerts for actionable interventions during the pandemic. We tested this promise in a cohort of SNFs patients diagnosed with COVID-19 and admitted for post-acute care under quarantine. We tested if 1) deployment of wearables and contact-free biosensors is feasible in the setting of SNFs and 2) they can provide early and actionable insights into deterioration.

MethodsThis prospective clinical trial has been IRB-approved (NCT04548895). We deployed two commercially available devices detecting continuously every 2-3 minutes heart rate (HR), respiratory rate (RR) and uniquely providing the following biometrics: 1) the wrist-worn bracelet by Biostrap yielded continuous oxygen saturation (O2Sat), 2) the under-mattress ballistocardiography sensor by Emfit tracked in-bed activity, tossing, and sleep disturbances. Patients also underwent routine monitoring by staff every 2-4 h. For death outcomes, cases are reported due to the small sample size. For palliative care versus at-home discharges, we report mean{+/-}SD at p<0.05.

ResultsFrom 12/2020 - 03/2021, we approached 26 PCR-confirmed SarsCoV2-positive patients at two SNFs: 5 declined, 21 were enrolled into monitoring by both sensors (female=13, male=8; age 77.2{+/-}9.1). We recorded outcomes as discharged to home (8, 38%), palliative care (9, 43%) or death (4, 19%). The O2Sat threshold of 91% alerted for intervention. Biostrap captured hypoxic events below 91% nine times as often as the routine intermittent pulse oximetry. In the patient deceased, two weeks prior we observed a wide range of O2Sat values (65-95%) captured by the Biostrap device and not noticeable with the routine vital sign spot checks. In this patient, the Emfit sensor yielded a markedly reduced RR (7/min) in contrast to 18/min from two routine spot checks performed in the same period of observation as well as compared to the seven patients discharged home over a total of 86 days of monitoring (RR 19{+/-} 4). Among the patients discharged to palliative care, a total of 76 days were monitored, HR did not differ compared to the patients discharged home (68{+/-}8 vs 70{+/-}7 bpm). However, we observed a statistically significant reduction of RR at 16{+/-}4/min as well as the variances in RR (10{+/-}6 vs 19{+/-}4/min vs16{+/-}13) and activity of palliative care patients vs. patients discharged home.

Conclusion/DiscussionWe demonstrate that wearables and under-mattress sensors can be integrated successfully into the SNF workflows and are well tolerated by the patients. Moreover, specific early changes of oxygen saturation fluctuations and other biometrics herald deterioration from COVID-19 two weeks in advance and evaded detection without the devices. Wearable devices and under-mattress sensors in SNFs hold significant potential for early disease detection.


title: Impact of the COVID-19 epidemic on mortality in rural coastal Kenya

abstract:
BackgroundThe impact of COVID-19 on all-cause mortality in sub-Saharan Africa remains unknown.

MethodsWe monitored mortality among 306,000 residents of Kilifi Health and Demographic Surveillance System, Kenya, through four COVID-19 waves from April 2020-September 2021. We calculated expected deaths using negative binomial regression fitted to baseline mortality data (2010-2019) and calculated excess mortality as observed-minus-expected deaths. We excluded deaths in infancy because of under-ascertainment of births during lockdown. In February 2021, after two waves of wild-type COVID-19, adult seroprevalence of anti-SARS-CoV-2 was 25.1%. We predicted COVID-19-attributable deaths as the product of age-specific seroprevalence, population size and global infection fatality ratios (IFR). We examined changes in cause of death by Verbal Autopsy (VA).

ResultsBetween April 2020 and February 2021, we observed 1,000 deaths against 1,012 expected deaths (excess mortality -1.2%, 95% PI -6.6%, 5.8%). Based on SARS-CoV-2 seroprevalence, we predicted 306 COVID-19-attributable deaths (a predicted excess mortality of 30.6%) within this period. Monthly mortality analyses showed a significant excess among adults aged [≥]45 years in only two months, July-August 2021, coinciding with the fourth (Delta) wave of COVID-19. By September 2021, overall excess mortality was 3.2% (95% PI -0.6%, 8.1%) and cumulative excess mortality risk was 18.7/100,000. By VA, there was a transient reduction in deaths attributable to acute respiratory infections in 2020.

ConclusionsNormal mortality rates during extensive transmission of wild-type SARS-CoV-2 through February 2021 suggests that the IFR for this variant is lower in Kenya than elsewhere. We found excess mortality associated with the Delta variant but the cumulative excess mortality risk remains low in coastal Kenya compared to global estimates.


title: Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study

abstract:
BackgrounCommon pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in offspring and these associations might differ with offspring age.

MethodsWe used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1-1.6y), childhood (4.2-7.5y); adolescence (12.0-16.0y), and adulthood (22.0-67.8y).

ResultsOffspring numbers for each age category/analysis varied from 8,925 adults (441 PTB) to 1,181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P[≤]0.001) with some limited evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of -0.89 standard deviation (SD) units for albumin with PTB (95%CI: -1.10 to -0.69, P=1.3x10-17) and -0.41SD for total lipids in medium HDL with SGA (95%CI: -0.56 to -0.25, P=2.6x10-7), with limited evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g., -0.11SD total fatty acids, 95%CI: -0.18 to -0.05, P=0.0009), and attenuating with older age across adulthood.

ConclusionsThese reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for new-borns rather than older ages, and for perinatal rather than pregnancy complications.


title: Vaccine effectiveness of BNT162b2 against Omicron and Delta outcomes in adolescents

abstract:
IntroductionData on vaccine effectiveness (VE) against Omicron in adolescents are limited. We estimated 2-dose and 3-dose VE against Omicron and Delta in adolescents aged 12-17 years in Ontario, Canada.

MethodsWe conducted a test-negative design study among SARS-CoV-2-tested adolescents aged 12-17 years between November 22, 2021 (date of first Omicron detection) and March 6, 2022; we assessed Delta outcomes prior to January 2, 2022. We used multivariable logistic regression to compare the odds of vaccination in cases to symptomatic test-negative controls and calculated VE as 1-adjusted odds ratio.

ResultsVE was lower against symptomatic Omicron infection than against Delta and decreased more rapidly over time, from 51% (95%CI, 38-61%) in the 7-59 days following a second dose to 29% (95%CI, 17-38%) after 180 days, compared to 97% (95%CI, 94-99%) and 90% (95%CI, 79-95%) for the same intervals against symptomatic Delta infection. Overall, 2-dose VE against severe outcomes caused by Omicron was 85% (95%CI, 74-91%) [≥]7 days following a second dose and estimates were similar over time. VE against symptomatic Omicron infection was 62% (95%CI, 49-72%) [≥]7 days following a third dose.

DiscussionTwo-dose VE against symptomatic Omicron infection wanes over time in adolescents. While lower than observed against Delta, protection against severe outcomes appears to be maintained over time. A third dose substantially improves protection against Omicron infection, but 3-dose VE is only moderate at approximately 60% in the early period following vaccination and the duration of this protection is unknown.


title: Prevalence and Factors Associated with Chronic Kidney Disease among Patients Admitted to Medical Ward in a Tertiary Hospital, Northern Ethiopia, a Cross Sectional Study

abstract:
IntroductionChronic Kidney Disease (CKD) is being recognized as a global public health problem. CKD is a major non-communicable disease with the global prevalence varying between 10.5% and 13.1%. Diabetes and hypertension appear to be the leading causes of CKD and End Stage Renal Disease worldwide. The aim of this study is to determine the prevalence of CKD and its associated factors among patients admitted to medical ward in a tertiary hospital, Northern Ethiopia.

MethodologyAn institution based cross-sectional study was undertaken using systematic random sampling technique to select study participants. Sample sizes of 450 patients were included in the study. Data was collected using a pre-tested semi-structured questionnaire designed to meet the study objective. The data collection period was from October 20, 2017 to March 20, 2018 G.C. Data was analyzed using SPSS version 21.The odds ratio with their 95% confidence interval and P value were calculated. Statistical significance was declared if P value < 0.05.

ResultOf the 450 patients, 260(57.8%) were males. More than half (54.2%) were between ages of 25 to 40 years. The overall prevalence of CKD among patients admitted to medical ward was 17.3% (95% CI 13 - 29.9) and 14.4% (95 % CI 6.2 - 12.3) by Cockcroft Gault and MDRD equations respectively. Prevalence of stage 5 CKD was 61.5% by Cockcroft Gault equation. Hypertension AOR 3(95%CI 1.28, 4.1), history of recurrent urinary tract infection AOR 3.5 (95% CI 1.1, 7.3) and history of using nephrotoxic drugs AOR 3.4 (95% CI 2, 9.3) were significantly associated with CKD.

ConclusionThe prevalence of CKD among adult patients admitted to medical ward in tertiary hospital, Northern Ethiopia was high and majority of patients with CKD were stage 5. Hypertension, use of nephrotoxic agents and recurrent urinary tract infections were significantly associated with CKD.

category: nephrology