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Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study

J Clin Immunol. 2021 Jul 17. doi: 10.1007/s10875-021-01083-7. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship of host immune response and viral replication with health outcomes in patients with COVID-19 remains to be defined. We aimed to characterize the medium and long-term clinical, virological, and serological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID.

METHODS: Prospective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2, and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID-19 symptom questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized.

RESULTS: Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2 months and 6 months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct = 38) and 3% (median Ct = 36) patients at 2 months and 6 months, respectively, but no reinfections were demonstrated. Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR [95%CI]) were lower peak S-IgG (0.80 [0.66-0.94]) and higher WHO severity score (2.57 [1.20-5.86]); 6-month predictors were lower peak S-IgG (0.89 [0.79-0.99]) and female sex (2.41 [1.20-4.82]); no association was found with prolonged viral RNA shedding.

CONCLUSIONS: Long-COVID is associated with weak anti-SARS-CoV-2 antibody response, severity of illness, and female gender. Late clinical events and persistent symptoms in the medium and long term occur in a significant proportion of patients hospitalized for COVID-19.

PMID:34273064 | DOI:10.1007/s10875-021-01083-7

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Effects of fuel change to electricity on PM2.5 local levels in the Bus Rapid Transit System of Bogota

Environ Sci Pollut Res Int. 2021 Jul 17. doi: 10.1007/s11356-021-14978-0. Online ahead of print.

ABSTRACT

The TransMilenio (TM) is a transport system. Twenty-year-old TM is a fast, highly efficient, and self-sufficient mode of passenger transport. This work aims to evaluate the effects of changing current TM diesel buses by electricity-powered buses (battery, wire-based), on the PM2.5 concentrations at surface level. Emissions calculations considering combustions and resuspension of TM and Non-TM were performed. A CFD model was implemented to estimate current PM2.5 concentrations at the roadside level, and the CFD results were validated using the statistic parameters: MB, RMSE, r, and IOA. Results from the emission calculations indicate that TM buses (30-50%) are one of the main sources of primary PM2.5 in all the considered urban sites in this study. Non-exhaust emissions from most vehicle categories were also identified as an important source of primary PM2.5 (40% of total emissions). The CFD model reproduced closely the trends and levels of PM2.5 concentrations measured at the roadside level in all the locations. Replacing TM diesel vehicles with electric vehicles reduces PM2.5 concentrations between 10 and 30% according to the CFD results obtained. Higher reductions can be achieved if policies are adopted to control other types of vehicles and non-exhaust emissions since they have a contribution of about 60%. Finally, this study shows that the combined use of emission calculations and advanced near-road dispersion models are useful tools to study and manage air quality in large cities.

PMID:34273076 | DOI:10.1007/s11356-021-14978-0

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Atomoxetine and circadian gene expression in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder

J Neural Transm (Vienna). 2021 Jul 17. doi: 10.1007/s00702-021-02373-5. Online ahead of print.

ABSTRACT

Atomoxetine (ATO) is a second line medication for attention-deficit hyperactivity disorder (ADHD). We proposed that part of the therapeutic profile of ATO may be through circadian rhythm modulation. Thus, the aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after ATO exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with a diagnosis of ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different ATO concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. No statistical significant effect of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, sleep WASO and total number of wake bouts was observed. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. ATO induced the rhythmicity of Clock in the ADHD group. This effect, however, was not observed in HDF cultures of healthy controls. Bmal1 and Per2 expression showed a significant ZT × group interaction via mixed ANOVA. Strong positive correlations for chronotype and circadian genes were observed for Bmal1, Cry1 and Per3 among the study participants. Statistical significant different Clock, Bmal1 and Per3 expressions were observed in HDFs exposed to ATO collected from ADHD participants exhibiting neutral and moderate evening preference, as well as healthy participants with morning preferences. The results of the present study illustrate that ATO impacts on circadian function, particularly on Clock, Bmal1 and Per2 gene expression.

PMID:34273025 | DOI:10.1007/s00702-021-02373-5

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Distress among cancer patients attending rehabilitation in the community

Support Care Cancer. 2021 Jul 17. doi: 10.1007/s00520-021-06422-3. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to identify sources of distress among cancer patients attending rehabilitation in the community.

METHODS: Participants were 430 patients recruited from a cancer rehabilitation center in Singapore between 2017 and 2018, who had rated their distress using the distress thermometer (DT) and indicated associated problems on the problem list. Chi-square tests were used to detect differences in the reported symptoms among three age groups. Exploratory factor analysis was used to identify symptom clusters. Partial correlational analysis was then performed to examine the relationship between distress, symptom clusters, and age controlling for gender and cancer type.

RESULTS: About 30% of the participants reported distress ≥ 5 on the DT (mean 3.3 ± 2.5), and the mean number of problems endorsed was 8 ± 6. A higher total number of reported problems (r = .63) and younger age (r = – .21) were associated with increased distress. The younger age group also reported more problems surrounding emotions, finance, work/school, children-related issues, and physical symptoms such as sleep and nausea. Of the 12 factors identified, 9 psychosocial and physical symptom clusters correlated with distress (r ranging from .12 to .41). All results were statistically significant after adjustment (p ≤ 0.05).

CONCLUSION: Younger survivors are more at risk of distress and report greater role functioning concerns related to childcare, partner relationship, and work participation. Age-tailored and multimodal interventions may be necessary to adequately address age-related differences and help coordinate management of multiple symptom clusters across physical and psychosocial concerns.

PMID:34273033 | DOI:10.1007/s00520-021-06422-3

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Early postoperative pain as a marker of anastomotic leakage in colorectal cancer surgery

Int J Colorectal Dis. 2021 Jul 17. doi: 10.1007/s00384-021-03984-w. Online ahead of print.

ABSTRACT

PURPOSE: Even though anastomotic leakage after colorectal surgery is a major clinical problem in need of a timely diagnosis, early indicators of leakage have been insufficiently studied. We therefore conducted a population-based observational study to determine whether the patient’s early postoperative pain is an independent marker of anastomotic leakage.

METHODS: By combining the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry, we retrieved prospectively collected data on 3084 patients who underwent anastomotic colorectal surgery for cancer in 2014-2017. Postoperative pain, measured with the numerical rating scale (NRS), was considered exposure, while anastomotic leakage and reoperation due to leakage were outcomes. We performed logistic regression to evaluate associations, estimating odds ratios (ORs) and 95% confidence intervals (CIs), while multiple imputation was used to handle missing data.

RESULTS: In total, 189 patients suffered from anastomotic leakage, of whom 121 patients also needed a reoperation due to leakage. Moderate or severe postoperative pain (NRS 4-10) was associated with an increased risk of anastomotic leakage (OR 1.69, 95% CI 1.21-2.38), as well as reoperation (OR 2.17, 95% CI 1.41-3.32). Severe pain (NRS 8-10) was more strongly related to leakage (OR 2.38, 95% CI 1.44-3.93). These associations were confirmed in multivariable analyses and when reoperation due to leakage was used as an outcome.

CONCLUSION: In this population-based retrospective study on prospectively collected data, increased pain in the post-anaesthesia care unit is an independent marker of anastomotic leakage, possibly indicating a need for further diagnostic measures.

PMID:34272996 | DOI:10.1007/s00384-021-03984-w

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Three-dimensional craniofacial characteristics associated with obstructive sleep apnea severity and treatment outcomes

Clin Oral Investig. 2021 Jul 17. doi: 10.1007/s00784-021-04066-5. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aims to assess craniofacial dimensions in obstructive sleep apnea (OSA) patients treated with a mandibular advancement device (MAD) and to identify anatomic influences on OSA severity and MAD therapy outcomes.

MATERIALS AND METHODS: Twenty patients with OSA were prospectively treated with MAD. Clinical, cone-beam computed tomography, and polysomnography exams were performed before treatment and 4-6 months after achieving the MAD therapeutic position. Polysomnographic exams and three-dimensional maxillary, mandibular, and upper airway (UA) measurements were evaluated. Pearson’s correlation and t-tests were applied.

RESULTS: Before MAD treatment, the transverse width measured at the frontomaxillary suture and the angle between the mandibular ramus and Frankfurt horizontal were statistically correlated with apnea and the hypopnea index (AHI), while the gonial angle was correlated with therapeutic protrusion. After MAD treatment, all patients showed a significant AHI reduction and an improvement in minimum oxyhemoglobin saturation. The UA total volume, superior and inferior oropharynx volume, and area were statistically correlated with MAD therapeutic protrusion. The UA total area showed a statistical correlation with the improvement in AHI, and the superior oropharynx volume and area increased significantly.

CONCLUSIONS: The transversal frontomaxillary suture width and the mandibular ramus facial angle may influence OSA severity. The gonial angle, volume, and area of all UA regions may indicate the amount of protrusion needed for successful MAD treatment.

CLINICAL RELEVANCE: The craniofacial characteristics reported as important factors for OSA severity and MAD treatment outcomes impact therapy planning for OSA patients, considering individual anatomic characteristics, prognosis, and cost benefits.

PMID:34273012 | DOI:10.1007/s00784-021-04066-5

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The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration

J Perinat Med. 2021 Jul 15. doi: 10.1515/jpm-2021-0048. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination.

METHODS: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks’ gestation, rate of admission to neonatal intensive care unit (NICU).

RESULTS: In total, 130 cases were included. “PAMG-1 group” consisted of 68 women, 62 cases built the “historical control group”. ACS administration was performed less frequently in the “PAMG-1 cohort” (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks’ gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks’ gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the “historical control group” (22 (38%) vs. 28 (60%); p=0.0272).

CONCLUSIONS: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.

PMID:34271603 | DOI:10.1515/jpm-2021-0048

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Birth and death notification via mobile devices: a mixed methods systematic review

Cochrane Database Syst Rev. 2021 Jul 16;7:CD012909. doi: 10.1002/14651858.CD012909.pub2.

ABSTRACT

BACKGROUND: Ministries of health, donors, and other decision-makers are exploring how they can use mobile technologies to acquire accurate and timely statistics on births and deaths. These stakeholders have called for evidence-based guidance on this topic. This review was carried out to support World Health Organization (WHO) recommendations on digital interventions for health system strengthening.

OBJECTIVES: Primary objective: To assess the effects of birth notification and death notification via a mobile device, compared to standard practice. Secondary objectives: To describe the range of strategies used to implement birth and death notification via mobile devices and identify factors influencing the implementation of birth and death notification via mobile devices.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Global Health Library, and POPLINE (August 2, 2019). We searched two trial registries (August 2, 2019). We also searched Epistemonikos for related systematic reviews and potentially eligible primary studies (August 27, 2019). We conducted a grey literature search using mHealthevidence.org (August 15, 2017) and issued a call for papers through popular digital health communities of practice. Finally, we conducted citation searches of included studies in Web of Science and Google Scholar (May 15, 2020). We searched for studies published after 2000 in any language. SELECTION CRITERIA: For the primary objective, we included individual and cluster-randomised trials; cross-over and stepped-wedge study designs; controlled before-after studies, provided they have at least two intervention sites and two control sites; and interrupted time series studies. For the secondary objectives, we included any study design, either quantitative, qualitative, or descriptive, that aimed to describe current strategies for birth and death notification via mobile devices; or to explore factors that influence the implementation of these strategies, including studies of acceptability or feasibility. For the primary objective, we included studies that compared birth and death notification via mobile devices with standard practice. For the secondary objectives, we included studies of birth and death notification via mobile device as long as we could extract data relevant to our secondary objectives. We included studies of all cadres of healthcare providers, including lay health workers; administrative, managerial, and supervisory staff; focal individuals at the village or community level; children whose births were being notified and their parents/caregivers; and individuals whose deaths were being notified and their relatives/caregivers.

DATA COLLECTION AND ANALYSIS: For the primary objective, two authors independently screened all records, extracted data from the included studies and assessed risk of bias. For the analyses of the primary objective, we reported means and proportions, where appropriate. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence and we prepared a ‘Summary of Findings’ table. For the secondary objectives, two authors screened all records, one author extracted data from the included studies and assessed methodological limitations using the WEIRD tool and a second author checked the data and assessments. We carried out a framework analysis using the Supporting the Use of Research Evidence (SURE) framework to identify themes in the data. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in the evidence and we prepared a ‘Summary of Qualitative Findings’ table.

MAIN RESULTS: For the primary objective, we included one study, which used a controlled before-after study design. The study was conducted in Lao People’s Democratic Republic and assessed the effect of using mobile devices for birth notification on outcomes related to coverage and timeliness of Hepatitis B vaccination. However, we are uncertain of the effect of this approach on these outcomes because the certainty of this evidence was assessed as very low. The included study did not assess resource use or unintended consequences. For the primary objective, we did not identify any studies using mobile devices for death notification. For the secondary objective, we included 21 studies. All studies were conducted in low- or middle-income settings. They focussed on identification of births and deaths in rural, remote, or marginalised populations who are typically under-represented in civil registration processes or traditionally seen as having poor access to health services. The review identified several factors that could influence the implementation of birth-death notification via mobile device. These factors were tied to the health system, the person responsible for notifying, the community and families; and include: – Geographic barriers that could prevent people’s access to birth-death notification and post-notification services – Access to health workers and other notifiers with enough training, supervision, support, and incentives – Monitoring systems that ensure the quality and timeliness of the birth and death data – Legal frameworks that allow births and deaths to be notified by mobile device and by different types of notifiers – Community awareness of the need to register births and deaths – Socio-cultural norms around birth and death – Government commitment – Cost to the system, to health workers and to families – Access to electricity and network connectivity, and compatibility with existing systems – Systems that protect data confidentiality We have low to moderate confidence in these findings. This was mainly because of concerns about methodological limitations and data adequacy.

AUTHORS’ CONCLUSIONS: We need more, well-designed studies of the effect of birth and death notification via mobile devices and on factors that may influence its implementation.

PMID:34271590 | DOI:10.1002/14651858.CD012909.pub2

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Knowledge of osteopathic manipulative medicine and osteopathic physicians in a New York South Asian community

J Osteopath Med. 2021 Jul 16. doi: 10.1515/jom-2021-0060. Online ahead of print.

ABSTRACT

CONTEXT: Research regarding patient awareness of osteopathic manipulative medicine (OMM) can help identify barriers and factors limiting patient knowledge. Levels of knowledge about OMM and osteopathic physicians have been studied in New York’s Chinese and Korean populations, but have not previously been investigated in the South Asian population.

OBJECTIVES: To assess the knowledge of OMM and osteopathic physicians within a South Asian community of New York.

METHODS: A cross-sectional study was designed in which a culturally appropriate survey, provided in both English and Hindi, was administered to study participants in order to measure knowledge of osteopathic medicine. The study utilized convenience sampling and distributed surveys to individuals who identified themselves of South Asian descent at high traffic sites in Hicksville, New York. The survey contained 10 questions, assessing the individual’s knowledge of osteopathic medicine. The Kruskal-Wallis and Chi-Square tests were employed to determine statistical significance of the data obtained from the surveys.

RESULTS: The survey was conducted on 100 participants in Hicksville, New York. The respondent demographics included 53 males and 47 females with an average age of 41.2 ± 16.3 years old. There were 34 (34%) participants who had heard of osteopathic manipulative medicine (OMM) and 26 (26%) participants who had knowledge of doctor of osteopathic medicine (DO) physicians. Respondents were found more likely to have knowledge of DOs if they were born in the United States (US) vs. other countries (US, 8 of 14 [57.1%] vs. others, 18 of 86 [20.9%]; p=0.006) or lived longer in the US (11 of 26 [42.3%], p=0.039). Participants who spoke a non-English primary language were also found less likely to have knowledge of DOs as they made up 46 of the 58 respondents who indicated no knowledge (79.3%, p=0.042).

CONCLUSIONS: A general lack of knowledge of DOs and OMM exists within the South Asian community of Hicksville, New York and lower levels of awareness were found among participants who were male, born outside the US, had a language other than English as their primary language, and had spent less time in the US. Additional educational resources may be implemented to increase awareness of DOs and OMM among this and similar communities.

PMID:34271600 | DOI:10.1515/jom-2021-0060

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Inference of ventricular activation properties from non-invasive electrocardiography

Med Image Anal. 2021 Jun 23;73:102143. doi: 10.1016/j.media.2021.102143. Online ahead of print.

ABSTRACT

The realisation of precision cardiology requires novel techniques for the non-invasive characterisation of individual patients’ cardiac function to inform therapeutic and diagnostic decision-making. Both electrocardiography and imaging are used for the clinical diagnosis of cardiac disease. The integration of multi-modal datasets through advanced computational methods could enable the development of the cardiac ‘digital twin’, a comprehensive virtual tool that mechanistically reveals a patient’s heart condition from clinical data and simulates treatment outcomes. The adoption of cardiac digital twins requires the non-invasive efficient personalisation of the electrophysiological properties in cardiac models. This study develops new computational techniques to estimate key ventricular activation properties for individual subjects by exploiting the synergy between non-invasive electrocardiography, cardiac magnetic resonance (CMR) imaging and modelling and simulation. More precisely, we present an efficient sequential Monte Carlo approximate Bayesian computation-based inference method, integrated with Eikonal simulations and torso-biventricular models constructed based on clinical CMR imaging. The method also includes a novel strategy to treat combined continuous (conduction speeds) and discrete (earliest activation sites) parameter spaces and an efficient dynamic time warping-based ECG comparison algorithm. We demonstrate results from our inference method on a cohort of twenty virtual subjects with cardiac ventricular myocardial-mass volumes ranging from 74 cm3 to 171 cm3 and considering low versus high resolution for the endocardial discretisation (which determines possible locations of the earliest activation sites). Results show that our method can successfully infer the ventricular activation properties in sinus rhythm from non-invasive epicardial activation time maps and ECG recordings, achieving higher accuracy for the endocardial speed and sheet (transmural) speed than for the fibre or sheet-normal directed speeds.

PMID:34271532 | DOI:10.1016/j.media.2021.102143