Tag: pubmed

PLoS One. 2022 Oct 27;17(10):e0274360. doi: 10.1371/journal.pone.0274360. eCollection 2022.

ABSTRACT

BACKGROUND: The COVID-19 pandemic had a severe impact on public life around the world, influencing medicine and health, the economy, employment, science, and education. Health care specialists are key workers who faced extreme challenges posed by the pandemic, including threats to their own lives due to the rapid spread of the virus, a huge increase in workload, and professional burnout syndrome. Analysis of the factors that physicians found most exhausting during the pandemic could lay the groundwork for the effective management of future crises.

OBJECTIVE: To identify the factors that physicians working in family physician (family and internal medicine) teams found most exhausting during the COVID-19 pandemic in Lithuania and assess their causes.

METHODS: An anonymous survey of physicians (n = 191) working in family physician teams was carried out from 21 June 2021 to 17 September 2021. Physicians signed an informed consent form prior to completion of the questionnaire. Mixed data analysis was performed, consisting of statistical analysis using the SPSS 27 software and a qualitative causal analysis.

RESULTS: During the pandemic, physicians were most exhausted by: chaotic vaccination priorities (44.5%); unsatisfied patients (52.4%); constantly changing legislation (71.7%); the large workload (75.9%); and the malfunctioning of online systems (81.2%).

CONCLUSIONS: Physicians in family physician teams indicated the following aspects that require improvement: service provision; effective work organization for physicians; and the satisfaction of patients with decisions made during the pandemic.

PMID:36301891 | DOI:10.1371/journal.pone.0274360

J Ultrasound Med. 2022 Oct 27. doi: 10.1002/jum.16117. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to present a comparison between panoramic radiographs and USG imaging with a focus on revealing the advantages of USG over radiographs, and to show the distribution of calcifications detected in USG by considering the age and gender.

METHODS: A total of 148 patients with soft tissue calcifications as seen on panoramic radiographs were examined with USG imaging. Sialoliths, carotid artery calcifications, tonsilloliths, phleboliths and lymph node calcifications were examined in terms of anatomical localization, distribution and shape.

RESULTS: In the USG evaluation of these 148 patients, soft tissue calcifications were observed in 113 (76.4%) patients. The mean age of the patients with calcification was 55.6 ± 13.1 (min: 22-max: 77). Bilateral calcifications were detected in 25 (22.1%) patients, whereas unilateral calcifications were found in 88 (77.9%) patients. While the rates of tonsilloliths, sialoliths, phleboliths, and lymph node calcifications were statistically similar in male and female patients, the rate of carotid artery calcifications was found to be higher in men than in women (P = 0.017). No statistical significance was found between age groups in terms of the formation of soft tissue calcifications (P = 0.117).

CONCLUSIONS: Panoramic radiographs may mislead clinicians in the diagnosis and differential diagnosis of soft tissue calcifications in the head and neck region due to the presence of distortion, superpositions, metal artefacts, and ghost images. USG is an important diagnostic tool in determining the localization of soft tissue calcifications that can be confused on two-dimensional radiographs, their relationship with neighboring structures, and defining calcification. It can be used safely in the detection of soft tissue calcifications as it provides dynamic imaging without the use of radiation or contrast material compared to other advanced imaging methods.

PMID:36301624 | DOI:10.1002/jum.16117

J Med Microbiol. 2022 Oct;71(10). doi: 10.1099/jmm.0.001595.

ABSTRACT

Introduction. Human bocavirus 1 (HBoV1) infection occurs with viral genome presence in respiratory secretions (RS) and serum, and therefore both samples can be used for diagnosis.Gap statement. The diagnostic sensitivity of HBoV1 DNA detection in serum and the duration of DNAaemia in severe clinical cases have not been elucidated.Aim. To determine HBoV1 DNA in serum and RS of paediatric patients hospitalized for lower acute respiratory infection (LARI) and to analyse the clinical-epidemiological features of positive cases.Methodology. This was a prospective, transverse study. Physicians selected the clinical situations and obtained paired clinical samples (RS and serum) that were tested by PCR/qPCR for HBoV1. Positive cases were analysed considering time of specimen collection, co-detection, clinical manifestations and viral load; statistical significant level was set at α=0.05.Results. HBoV1 was detected in 98 of 402 cases included (24 %); 18/98 (18 %) patients had the virus detectable in serum and 91/98 (93 %) in RS (P<0.001). Positivity rates were not significantly different in patients with RS and serum collected within or beyond 24 h of admission. Single HBoV1 infection was identified in 39/98 patients (40 %), three patients had HBoV1 in both clinical samples (3/39, 8 %) and 32 (32/39, 82 %) only in RS, 22 of them (69 %) with both clinical samples within 24 h of admission. Cough (P=0.001) and rhinitis (P=0.003) were significantly frequent among them and most patients were diagnosed with bronchiolitis (22/39, 56 %) and pneumonia (9/39, 23 %), which was more frequent compared to cases with co-infection (P=0.04). No significant differences were identified among patients with high, medium or low viral load of HBoV1 regarding rate of positivity in both clinical samples, the time of collection of RS and serum, co-detection, first episode of LARI, clinical manifestations, comorbidity or requirement for assisted ventilation. Intensive care unit (ICU) patients had a significantly higher frequency of detection (P<0.001) and co-detection (P=0.001) compared to patients on standard care.Conclusions. HBoV1 is prevalent among infant patients hospitalized for LARI and including it in the standard testing can add to the aetiological diagnosis in these cases, especially for patients admitted to the ICU. HBoV1 detection in serum did not contribute significantly to the diagnosis as compared to detection in respiratory secretions.

PMID:36301612 | DOI:10.1099/jmm.0.001595

Optom Vis Sci. 2022 Oct 25. doi: 10.1097/OPX.0000000000001954. Online ahead of print.

ABSTRACT

SIGNIFICANCE: Scleral lenses rely on the scleroconjunctival region without bearing the cornea, which could improve the symptoms and modify the corneal nerve plexus morphology.

PURPOSE: To evaluate symptoms and changes in corneal nerve plexus morphology and density of Langerhans cells in keratoconus patients with and without intrastromal corneal ring before and after scleral lens wear.

METHODS: Sixteen scleral lens wearers with keratoconus were recruited for this short-term experimental pilot study. Subjects were divided into two groups: keratoconus (KC group) and intrastromal corneal ring (KC-ICRS group). All subjects were examined in two visits: baseline (before scleral lens wear) and after six months of scleral lens wear, after lens removal. The Schirmer I test, Ocular Surface Disease Index (OSDI questionnaire), tear break-up time (TBUT) and in vivo confocal microscopy were evaluated.

RESULTS: The mean age was 42.33 ± 11.27 years. A significant decrease of TBUT was found in the total group (P = .01, Wilcoxon) compared with baseline. OSDI score had decreased after six months of scleral lenses wear in KC-ICRS subgroup (P = .03, Wilcoxon) and in total group (P = .001, Wilcoxon). No statistical changes in nerves density, tortuosity and ramification were found for the total group either subgroup. However, the mean nerves length was higher in all groups, especially in the keratoconus subgroup (P = .03, Wilcoxon) after 6 months of scleral lens wear. Regarding optical density, the total group showed a significant increase after 6 months of wearing, (P = .02, Wilcoxon). Finally, Langerhans cells density was not statistically different in any group.

CONCLUSIONS: These results suggest that scleral lens wearing improve the symptoms and increased the mean length nerves after six months of wear use in keratoconus patients.

PMID:36301598 | DOI:10.1097/OPX.0000000000001954

JAMA Otolaryngol Head Neck Surg. 2022 Oct 27. doi: 10.1001/jamaoto.2022.3282. Online ahead of print.

ABSTRACT

IMPORTANCE: Circulating tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA is a dynamic, clinically relevant biomarker for HPV-positive oropharyngeal squamous cell carcinoma. Reasons for its wide pretreatment interpatient variability are not well understood.

OBJECTIVE: To characterize clinicopathologic factors associated with TTMV HPV DNA.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients evaluated for HPV-positive oropharyngeal squamous cell carcinoma at Dana-Farber Cancer Institute in Boston, Massachusetts, between December 2019 and January 2022 and who were undergoing curative-intent treatment.

EXPOSURES: Clinicopathologic characteristics including demographic variables, tumor and nodal staging, HPV genotype, and imaging findings.

MAIN OUTCOMES AND MEASURES: Pretreatment circulating TTMV HPV DNA from 5 genotypes (16, 18, 31, 33, and 35) assessed using a commercially available digital droplet polymerase chain reaction-based assay, considered as either detectable/undetectable or a continuous score (fragments/mL).

RESULTS: Among 110 included patients, 96 were men (87%) and 104 were White (95%), with a mean (SD) age of 62.2 (9.4) years. Circulating TTMV HPV DNA was detected in 98 patients (89%), with a median (IQR) score of 315 (47-2686) fragments/mL (range, 0-60 061 fragments/mL). Most detectable TTMV HPV DNA was genotype 16 (n = 86 [88%]), while 12 patients (12%) harbored other genotypes. Circulating TTMV HPV DNA detection was most strongly associated with clinical N stage. Although few patients had clinical stage N0 disease, only 4 of these 11 patients (36%) had detectable DNA compared with 94 of 99 patients (95%) with clinical stage N1 to N3 disease (proportion difference, 59%; 95% CI, 30%-87%). Among patients with undetectable TTMV HPV DNA, more than half (7 of 12 [58%]) had clinical stage N0 disease. The TTMV HPV DNA prevalence and score increased with progressively higher clinical nodal stage, diameter of largest lymph node, and higher nodal maximum standardized uptake value on positron emission tomography/computed tomography. In multivariable analysis, clinical nodal stage and nodal maximum standardized uptake value were each strongly associated with TTMV HPV DNA score. Among 27 surgically treated patients, more patients with than without lymphovascular invasion had detectable TTMV HPV DNA (12 of 12 [100%] vs 9 of 15 [60%]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, circulating TTMV HPV DNA was statistically significantly associated with nodal disease at HPV-positive OPSCC diagnosis. The few patients with undetectable levels had predominantly clinical stage N0 disease, suggesting assay sensitivity for diagnostic purposes may be lower among patients without cervical lymphadenopathy. Mechanisms underlying this association, and the use of this biomarker for surveillance of patients with undetectable baseline values, warrant further investigation.

PMID:36301568 | DOI:10.1001/jamaoto.2022.3282

JAMA Ophthalmol. 2022 Oct 27. doi: 10.1001/jamaophthalmol.2022.4394. Online ahead of print.

ABSTRACT

IMPORTANCE: Dry eye is a common clinical manifestation, a leading cause of eye clinic visits, and a significant societal and personal economic burden in the United States. Meibomian gland dysfunction (MGD) is a major cause of evaporative dry eye.

OBJECTIVE: To conduct a systematic review and meta-analysis to obtain updated estimates of the prevalence and incidence of dry eye and MGD in the United States.

DATA SOURCES: Ovid MEDLINE and Embase.

STUDY SELECTION: A search conducted on August 16, 2021, identified studies published between January 1, 2010, and August 16, 2021, with no restrictions regarding participant age or language of publication. Case reports, case series, case-control studies, and interventional studies were excluded.

DATA EXTRACTION AND SYNTHESIS: The conduct of review followed a protocol registered on PROSPERO (CRD42021256934). PRISMA guidelines were followed for reporting. Joanna Briggs Institute and Newcastle Ottawa Scale tools were used to assess risk of bias. Data extraction was conducted by 1 reviewer and verified by another for accuracy. Prevalence of dry eye and MGD were combined in separate meta-analyses using random-effects models.

MAIN OUTCOMES AND MEASURES: Prevalence and incidence of dry eye and MGD in the United States. Summary estimates from meta-analysis of dry eye and MGD prevalence with 95% CI and 95% prediction intervals (95% PI).

RESULTS: Thirteen studies were included in the systematic review. Dry eye prevalence was reported by 10 studies, dry eye incidence by 2 studies, and MGD prevalence by 3 studies. Meta-analysis estimated a dry eye prevalence of 8.1% (95% CI, 4.9%-13.1%; 95% PI, 0%-98.9%; 3 studies; 9 808 758 participants) and MGD prevalence of 21.2% (95% CI, 7.2%-48.3%; 95% PI, 0%-100%; 3 studies; 19 648 participants). Dry eye incidence was 3.5% in a population 18 years and older and 7.8% in a population aged 68 years and older. No studies reported MGD incidence.

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis demonstrated uncertainty about the prevalence and incidence of dry eye and MGD in the United States. Population-based epidemiological studies that use consistent and validated definitions of dry eye and MGD are needed for higher-certainty estimates of dry eye and MGD prevalence and incidence in the United States.

PMID:36301551 | DOI:10.1001/jamaophthalmol.2022.4394

JAMA Otolaryngol Head Neck Surg. 2022 Oct 27. doi: 10.1001/jamaoto.2022.3316. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite growing scientific knowledge and research, it is still unknown if office flexible laryngoscopy (FL) is aerosol generating and thereby potentially increases the risk of SARS-CoV-2 transmission. The limited literature that exists is conflicting, precluding formal conclusions.

OBJECTIVE: To determine whether FL is aerosol generating.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 134 patients seen in the otolaryngology clinic at a single tertiary care academic institution between February and May 2021. Two optical particle sizer instruments were used, quantifying particles ranging from 0.02 μm to 5 μm. Measurements were taken every 30 seconds, with sample periods of 15 seconds throughout the patient encounter. Instruments were located 12 inches from the patient’s nares. Timing of events was recorded, including the start and end of physical examination, topical spray administration, start and end of laryngoscopy, and other potential aerosol-generating events (eg, coughing, sneezing). Data analysis was performed from February to May 2021.

EXPOSURES: Office examination and office FL.

MAIN OUTCOMES AND MEASURES: Bayesian online change point detection (OCPD) algorithm was used to detect significant change points (CPs) in this time-series data. The primary outcome was significant CP after FL compared with baseline physiologic variations, such as breathing and phonation.

RESULTS: Data were collected from 134 patients between February and May 2021. Ninety-one encounters involved FL. Of this group, 51 patients (56%) wore no mask over their mouth during FL. There was no statistically significant CP in either visits involving FL or visits where FL was not performed. Use of nasal spray did not result in CP in aerosol levels. Overall, neither the number of people present in the examination room, masks over patients’ mouth, the duration of the visit, nor the duration of FL were associated with mean aerosol counts, regardless of the exposure. For larger aerosol sizes (≥1 μm), however, rooms with higher air exchange rates had significantly higher reductions in mean aerosol counts for visits involving FL.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study support that FL, including topical spray administration, is not a significant aerosol-generating procedure. The Bayesian OCPD model has a promising application for future aerosol studies in otolaryngology.

PMID:36301539 | DOI:10.1001/jamaoto.2022.3316

JAMA Oncol. 2022 Oct 27. doi: 10.1001/jamaoncol.2022.5041. Online ahead of print.

ABSTRACT

IMPORTANCE: Management of checkpoint inhibitor-induced immune-related adverse events (irAEs) is primarily based on expert opinion. Recent studies have suggested detrimental effects of anti-tumor necrosis factor on checkpoint-inhibitor efficacy.

OBJECTIVE: To determine the association of toxic effect management with progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) in patients with advanced melanoma treated with first-line ipilimumab-nivolumab combination therapy.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, multicenter cohort study included patients with advanced melanoma experiencing grade 3 and higher irAEs after treatment with first-line ipilimumab and nivolumab between 2015 and 2021. Data were collected from the Dutch Melanoma Treatment Registry. Median follow-up was 23.6 months.

MAIN OUTCOMES AND MEASURES: The PFS, OS, and MSS were analyzed according to toxic effect management regimen. Cox proportional hazard regression was used to assess factors associated with PFS and OS.

RESULTS: Of 771 patients treated with ipilimumab and nivolumab, 350 patients (median [IQR] age, 60.0 [51.0-68.0] years; 206 [58.9%] male) were treated with immunosuppression for severe irAEs. Of these patients, 235 received steroids alone, and 115 received steroids with second-line immunosuppressants. Colitis and hepatitis were the most frequently reported types of toxic effects. Except for type of toxic effect, no statistically significant differences existed at baseline. Median PFS was statistically significantly longer for patients treated with steroids alone compared with patients treated with steroids plus second-line immunosuppressants (11.3 [95% CI, 9.6-19.6] months vs 5.4 [95% CI, 4.5-12.4] months; P = .01). Median OS was also statistically significantly longer for the group receiving steroids alone compared with those receiving steroids plus second-line immunosuppressants (46.1 months [95% CI, 39.0 months-not reached (NR)] vs 22.5 months [95% CI, 36.5 months-NR]; P = .04). Median MSS was also better in the group receiving steroids alone compared with the group receiving steroids plus second-line immunosuppressants (NR [95% CI, 46.1 months-NR] vs 28.8 months [95% CI, 20.5 months-NR]; P = .006). After adjustment for potential confounders, patients treated with steroids plus second-line immunosuppressants showed a trend toward a higher risk of progression (adjusted hazard ratio, 1.40 [95% CI, 1.00-1.97]; P = .05) and had a higher risk of death (adjusted hazard ratio, 1.54 [95% CI, 1.03-2.30]; P = .04) compared with those receiving steroids alone.

CONCLUSIONS AND RELEVANCE: In this cohort study, second-line immunosuppression for irAEs was associated with impaired PFS, OS, and MSS in patients with advanced melanoma treated with first-line ipilimumab and nivolumab. These findings stress the importance of assessing the effects of differential irAE management strategies, not only in patients with melanoma but also tumor types.

PMID:36301521 | DOI:10.1001/jamaoncol.2022.5041

J Cardiovasc Transl Res. 2022 Oct 27. doi: 10.1007/s12265-022-10335-9. Online ahead of print.

ABSTRACT

Neonatal coarctation of the aorta (CoA) is a common congenital heart defect. Its antenatal diagnosis remains challenging, and its pathophysiology is poorly understood. We present a novel statistical shape modeling (SSM) pipeline to study the role and predictive value of arch shape in CoA in utero. Cardiac magnetic resonance imaging (CMR) data of 112 fetuses with suspected CoA was acquired and motion-corrected to three-dimensional volumes. Centerlines from fetal arches were extracted and used to build a statistical shape model capturing relevant anatomical variations. A linear discriminant analysis was used to find the optimal axis between CoA and false positive cases. The CoA shape risk score classified cases with an area under the curve of 0.907. We demonstrate the feasibility of applying a SSM pipeline to three-dimensional fetal CMR data while providing novel insights into the anatomical determinants of CoA and the relevance of in utero arch anatomy for antenatal diagnosis of CoA.

PMID:36301513 | DOI:10.1007/s12265-022-10335-9

Methods Mol Biol. 2023;2575:305-321. doi: 10.1007/978-1-0716-2716-7_16.

ABSTRACT

Infectious agents often challenge therapeutics, from antibiotics resistance to antigenic variability affecting inoculation measures. Over the last decades, genome sequencing arose as an important ally to address such challenges. In bacterial infection, whole-genome-sequencing (WGS) supports tracking pathogenic alterations affecting the human microbiome. In viral infection, the analysis of the relevant sequence of nucleotides helps with determining historical variants of a virus and elucidates details about infection clusters and their distribution. Additionally, genome sequencing is now an important step in inoculation protocols, isolating target genes to design more robust immunisation assays. Ultimately, genetic engineering has empowered repurposing at scale, allowing long-lasting repeating clinical trials to be automated within a much shorter time-frame, by adjusting existing protocols. This is particularly important during sanitary emergencies as the ones caused by the 2014 West African Ebola outbreak, the Zika virus rapid spread in both South and North America in 2015, followed by Asia in 2016, and the pandemic caused by the SARS-CoV-2, which has infected more than 187 million people and caused more than 4 million deaths, worldwide, as per July 2021 statistics. In this scenery, this chapter presents a novel fully automated strategy to handle antigenic variability in immunisation protocols. The methodology comprises of two major steps (1) nanopore sequencing of infectious agent variants – the focus is on the SARS-CoV-2 and its variants; followed by (2) mRNA vector design for immunotherapy. This chapter presents the nanopore sequencing step and Chapter 17 introduces a protocol for mRNA vector design.

PMID:36301483 | DOI:10.1007/978-1-0716-2716-7_16