Time to resolution of respiratory and systemic coronavirus disease 2019 symptoms in community setting

ObjectivesTo assess the time to resolution of respiratory and systemic symptoms and their associated factors in outpatients during the coronavirus disease 2019 (COVID-19) pandemic.MethodsCohort study including adult outpatients, managed with Covidom, a telesurveillance solution, with RT-PCR-confirmed diagnosis, from 9 March 2020 until 23 February 2021. Follow up was 30 days after symptom onset.ResultsAmong the 9667 patients included, mean age was 43.2 ± 14.0 years, and 67.5% were female (n = 6522). Median body mass index (BMI) was 25.0 kg/m² (interquartile range 22.1–28.8 kg/m²). Main co-morbidities were: hypertension (12.9%; n = 1247), asthma (11.0%; n = 1063) and diabetes mellitus (5.5%; n = 527). The most frequent symptom during follow up was dyspnoea (65.1%; n = 6296), followed by tachypnoea (49.9%; n = 4821), shivers (45.6%; n = 4410) and fever (36.7%; n = 3550). Median times to resolution of systemic and respiratory symptoms were 3 days (95% CI 2−4 days) and 7 days (95% CI 6−8 days), respectively. Ultimately, 17.2% (95% CI 15.7%−18.8%) still presented respiratory symptoms at day 30. Longer time to respiratory symptom resolution was associated with older age, increased BMI, chronic obstructive pulmonary disease, coronary artery disease, asthma and heart failure. Regarding systemic symptoms, coronary artery disease, asthma, age above 40 years and elevated BMI were associated with longer time to resolution.ConclusionsTime to symptom resolution among outpatients with COVID-19 seemed shorter for systemic than respiratory symptoms. Prolonged respiratory symptoms were common at day 30. Risk factors associated with later resolution included age, and cardiovascular and pulmonary diseases.     

Aetiology of childhood hearing loss in Cameroon (sub-Saharan Africa)

BackgroundSevere hearing loss is a global problem affecting particularly developing countries. There is scarcity of recent published data on the epidemiology of childhood deafness in sub-Saharan Africa.ObjectiveTo determine the etiological profile of severe childhood deafness in Cameroon.MethodsProspective cross-sectional study of patients with a severe hearing loss that started before the age of 15 years. Detailed family and medical history was obtained; careful clinical, otological and audiological examinations were performed.ResultsA total of 582 patients with a severe hearing loss were examined. Prelingual deafness accounted for 75.1% (n = 437), with a mean age at medical diagnosis of 3.3 ± 1.2 years. This late presentation may be explained by limited parental awareness of signs raising suspicion of hearing loss, poor access to health care and the absence of neonatal screening for hearing loss in Cameroon. Identified genetic causes accounted for 14.8% (n = 86), putative environmental causes for 52.6% (n = 306) and unknown causes for 32.6% (n = 190). Amongst Genetic causes, the syndromic hearing loss accounted for 13.1% (n = 12) of cases, the rest being non syndromic (n = 74). Consanguineous families accounted for 5.7% (n = 33) of the whole sample, and 15.1% (n = 13) of genetic cases. No union between deaf parents was observed.ConclusionThese data highlight the possible predominance of putative environmental causes of childhood deafness in Cameroon, and emphasize the need for improved policies for prevention of infectious diseases and for neonatal hearing screening. However, further molecular analyses and targeted CT scan investigations are required to more accurately gauge the contribution of genetics etiologies.     

Pure post-pubertal yolk sac tumor of the testis: An extremely rare and aggressive entity

ContextPure post-pubertal yolk sac tumors (YSTs) are an extremely rare type of malignant germ cell tumor (GCT) that account for <1 % of testicular GCTs. Clinically, they are more aggressive compared to the more common pre-pubertal counterpart. The aim of this study is to analyze the clinical presentation, ancillary tests and clinical outcomes in addition to presenting a spectrum of histomorphological features, in a case series along with a literature review.DesignA retrospective review of 4 cases of pure post-pubertal YST of the testis was performed.Data collected for each patient included demographics, clinical presentation, serum markers, radiology and pathologic findings, treatment, and clinical outcomes.ResultsAll patients presented with a testicular mass with or without associated pain and elevated serum alpha-feto protein. Mean age at presentation was 36 years (range 25–68 years). Two patients presented with metastatic disease at the time of diagnosis. Histologic patterns and features are as follows: germ cell neoplasia in-situ (n = 4), reticular/microcystic, solid, glandular, papillary, endometrioid, cystic, necrosis and angiolymphatic invasion (n = 3). Fluorescent in-situ hybridization test performed on Case 2, showed presence of isochromosome 12p and next generation sequencing showed gains of 12p. Case 1, 2 and 4 showed metastatic disease on follow-up.ConclusionsDiagnosis of pure post-pubertal YST remains challenging due to the variety of morphologic patterns often present in these tumors. Extensive sampling along with use of ancillary tests is the key for diagnosis. In this study, 75 % of cases had metastatic disease at or after the diagnosis confirming the aggressive nature of this rare entity.     

Clinical sequelae of COVID-19 survivors in Wuhan,China: a single-centre longitudinal study

ObjectivesTo describe the prevalence, nature and risk factors for the main clinical sequelae in coronavirus disease 2019 (COVID-19) survivors who have been discharged from the hospital for more than 3 months.MethodsThis longitudinal study was based on a telephone follow-up survey of COVID-19 patients hospitalized and discharged from Renmin Hospital of Wuhan University, Wuhan, China before 1 March 2020. Demographic and clinical characteristics and self-reported clinical sequelae of the survivors were described and analysed. A cohort of volunteers who were free of COVID-19 and lived in the urban area of Wuhan during the outbreak were also selected as the comparison group.ResultsAmong 538 survivors (293, 54.5% female), the median (interquartile range) age was 52.0 (41.0–62.0) years, and the time from discharge from hospital to first follow-up was 97.0 (95.0–102.0) days. Clinical sequelae were common, including general symptoms (n = 267, 49.6%), respiratory symptoms (n = 210, 39%), cardiovascular-related symptoms (n = 70, 13%), psychosocial symptoms (n = 122, 22.7%) and alopecia (n = 154, 28.6%). We found that physical decline/fatigue (p < 0.01), postactivity polypnoea (p= 0.04) and alopecia (p < 0.01) were more common in female than in male subjects. Dyspnoea during hospitalization was associated with subsequent physical decline/fatigue, postactivity polypnoea and resting heart rate increases but not specifically with alopecia. A history of asthma during hospitalization was associated with subsequent postactivity polypnoea sequela. A history of pulse ≥90 bpm during hospitalization was associated with resting heart rate increase in convalescence. The duration of virus shedding after COVID-19 onset and hospital length of stay were longer in survivors with physical decline/fatigue or postactivity polypnoea than in those without.ConclusionsClinical sequelae during early COVID-19 convalescence were common; some of these sequelae might be related to gender, age and clinical characteristics during hospitalization.     

Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study

ObjectiveDiscriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses.MethodsChildren with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls.ResultsMxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 μg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78–99%) sensitivity and 100% (95% CI: 51–100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 μg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 μg/l, interquartile range: 679 to 2489).DiscussionMxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.     

Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers; COVIDSTORM—a prospective,randomized, single-centre,open-label study

ObjectivesSevere COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage.MethodsPatients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission.ResultsClinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7–12) in the TCZ group and 12 days (interquartile range, 9–15) in the control group (p = 0.014).DiscussionIn patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone.     

Extrapulmonary tuberculosis among migrants in Europe, 1995 to 2017

ObjectivesThe proportion of tuberculosis (TB) cases occurring in migrants in Europe is increasing. Extrapulmonary TB poses challenges in diagnosis and treatment and causes serious morbidity and mortality, yet its extent in migrant populations is unclear. We assessed patterns of extrapulmonary TB in migrants across the European Union (EU)/European Free Trade Association (EFTA). We investigated the proportion of extrapulmonary TB cases among migrants versus non-migrants, and variations by specific site of disease, reporting European region, and migrant region of origin.MethodsWe carried out a cross-sectional secondary database analysis, utilizing 23 years of data collected between 1995 and 2017 from the European Surveillance System of the European Centre for Disease Prevention and Control for 32 EU/EFTA countries.ResultsIn total, 1 270 896 TB cases were included, comprising 326 987 migrants (25.7%) and 943 909 non-migrants (74.3%). Of TB cases among migrants, 45.2% (n = 147 814) were extrapulmonary compared to 21.7% (n = 204 613) among non-migrants (p < 0.001). Lymphatic, bone/joint and peritoneal/digestive TB were more common among migrant than non-migrant extrapulmonary cases. A lower proportion of extrapulmonary TB was seen in Eastern Europe (17.4%, n = 98 656 of 566 170) and Southern Europe (29.6%, n = 62 481 of 210 828) compared with Western (35.7%, n = 89 498 of 250 517) and Northern Europe (41.8%, n = 101 792 of 243 381). Migrants from South-East Asia and Sub-Saharan Africa were at highest risk of extrapulmonary disease, with 62.0% (n = 55 401 of 89 353) and 54.5% (n = 38 327 of 70 378) of cases, respectively, being extrapulmonary.ConclusionsAmong TB cases in the EU/EFTA, extrapulmonary disease is significantly more common in migrants than in non-migrants. There is a need to improve clinical awareness of extrapulmonary TB and to integrate its detection into screening programmes.     

Repeated introduction and spread of the MRSA clone t304/ST6 in northern Europe

ObjectivesDuring the last decades several methicillin-resistant Staphylococcus aureus (MRSA) clones with the capability of global spread have emerged in the community. Here, we have investigated a large collection of clinical isolates belonging to MRSA clone t304/ST6, which has emerged in many European countries over the last years, in order to retrace its phylogeny and its spread.MethodsWe characterized 466 ST6 isolates from Denmark (n = 354), France (n = 10), Norway (n = 24), Sweden (n = 27) and the UK (n = 51). All had spa-type t304 (n = 454) or t304-related spa-types (n = 12) and whole genome sequencing (WGS) was carried out on Illumina Miseq or Hiseq with 100–300 bp reads. cgMLST was performed using Ridom SeqSphere.ResultsA minimum spanning tree (MST) of all 466 isolates showed one large cluster including 182 isolates collected only from Denmark and related to a long-term neonatal outbreak in Copenhagen. This cluster contrasted with numerous small clusters, including the remaining Danish isolates and isolates from the other countries that interspersed throughout the tree. Most isolates were Panton-Valentine leukocidin (PVL) negative (95%) and harboured SCCmec IVa. One genome was closed using Oxford Nanopore technology and Illumina MiSeq. It contained a plasmid of 19.769 bp including the blaZ gene. A similar plasmid was found in 78% of all isolates.Discussiont304/ST6 is a successful emerging clone and the fact that isolates from five countries are interspersed throughout the MST indicates a common origin. This clone is commonly described in the Middle East and its emergence in Europe coincides with influx of refugees from the Syrian Civil War.     

Hepatitis E virus seroprevalence in three hyperendemic areas: Nepal,Bangladesh and southwest France

BackgroundHepatitis E causes a significant burden of disease in developing countries and has recently been increasingly recognized in developed countries. Comparing population anti-hepatitis E virus (HEV) seroprevalence across populations has been difficult.ObjectivesThe aim of this study was to compare the anti-HEV IgG seroprevalence in both adults and children in three hyper-endemic areas (Nepal, Bangladesh and southwest France) using a sensitive, commercial anti-HEV IgG assay.Study DesignSerum or plasma from adults and children in Nepal (n=498), Bangladesh (n = 1,009) and Southwest France (n = 1031) were tested for anti-HEV IgG using the Wantai assay.ResultsAfter age-standardization, anti-HEV IgG seroprevalence was 47.1%, 49.8% and 34.0% in Nepal, Bangladesh and southwest France, respectively. There was no difference in seroprevalence by gender in any of the countries. A paucity of infections in children 1–10 years-old was consistently observed (less than 15%) at all 3 locations.ConclusionsSurprisingly similar high rates of anti-HEV antibodies were detected using a common, sensitive assay. Despite differences in the epidemiology and circulating genotype of HEV in Nepal, Bangladesh and southwest France, this study found more similarities in population seroprevalence than expected.     

Impact of variants of uncertain significance of LDL receptor on phenotypes of familial hypercholesterolemia

BackgroundData on the effect of variants of uncertain significance (VUS) of LDL receptor (LDLR) on familial hypercholesterolemia (FH) phenotype is limited.ObjectiveTo investigate the associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and occurrence of major adverse cardiac events (MACEs), in FH patients (N = 1050, male/female = 490/560).MethodsWe retrospectively assessed the data of patients with FH admitted at Kanazawa University Hospital between 1990 and 2020. Based on genotype, the patients were divided into patients without variants, with VUS of LDLR, and with pathogenic variants. Cox proportional hazard model was used to identify the factors associated with MACEs.ResultsThe median follow-up duration was 12.6 years (interquartile range: 9.5–17.9 years). Altogether, 777 patients had FH mutation and 273 had pathogenic mutation, with 92 having VUS. Over the follow-up duration, 175 MACEs were observed. LDL cholesterol level was found to be significantly higher in patients with pathogenic variants (251 mg/dL) than in patients with VUS (225 mg/dL) and without variants (203 mg/dL). Pathogenic variants and VUS are significantly associated with MACEs (hazard ratio [HR] = 1.52, 95% confidence interval [CI] = 1.02–2.02, P = 0.033 and HR = 3.18, 95% CI = 2.00–4.36, P = 1.9 × 10^?5, relative to patients without any variants, respectively), independent of classical risk factors.ConclusionVUS of LDLR was significantly associated with poor outcomes in FH patients. Genetic testing is useful for the diagnosis and risk stratification of FH patients.     

Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, “undifferentiated small round cell tumors”. A clinicopathologic,immunophenotypic and molecular analysis

BackgroundDespite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findings, a group of round/ovoid cell tumors histologically similar to Ewing sarcomas (ES) but lacking EWSR1-rearrangements may remain unclassifiable.DesignWe retrospectively analyzed 41 Ewing-like tumors (formalin-fixed, paraffin-embedded) previously determined as negative or non-informative for EWSR1-rearrangements by FISH and/or RT-PCR. A new histopathology revision and additional IHC and molecular analyses were carried out in order to investigate whether additional IHC and/or molecular testing in combination with the morphological findings may help in reaching a definitive diagnosis.ResultsAlmost all the tumors (n = 40) involved soft tissue and/or bone and half the patients died of disease. In the archival cases all diagnoses were Ewing sarcoma (ES), Ewing-like sarcoma (ELS), myoepithelial tumor and undifferentiated sarcoma (US). In the new review all the tumors were re-classified as, ES (n = 16), Ewing-like tumor with EWSR1 rearrangement and amplification and possible EWSR1-NFATC2 gene fusion (n = 1), CIC-rearranged sarcomas or undifferentiated sarcoma, most consistent with CIC-rearranged sarcoma (n = 7), sarcoma with BCOR-alteration or undifferentiated sarcoma, consistent with BCOR-associated sarcoma (n = 3), neuroblastoma (n = 2), unclassifiable neoplasm with neuroblastic differentiation (n = 1), malignant rhabdoid tumor (n = 2), lymphoblastic lymphoma (n = 1), clear cell sarcoma of the gastrointestinal tract (n = 1), small cell carcinoma (n = 1), sclerosing rhabdomyosarcoma (n = 1), desmoplastic small round cell tumor (n = 1), malignant peripheral sheath nerve tumor (n = 1), poorly-differentiated synovial sarcoma (n = 1), Possible gastrointestinal stromal tumor/GIST with predominant round cells (n = 1) and possible SMARCA4-deficient-sarcoma (n = 1). NKX2.2, ETV4 and BCOR immunoreactivity was observed in all ES, CIC-rearranged sarcomas and sarcomas with BCOR alteration, respectively. CIC-rearrangement by FISH was observed in many of the CIC-rearranged sarcomas.ConclusionOur analysis of 41 Ewing-like tumors confirms that there may be a significant pathological and IHC overlap among Ewing-like tumors, with prognostic and therapeutic impacts. Additional IHC (NKX2.2, ETV4 and BCOR) and molecular studies including FUS, CIC or BCOR analysis may support the final diagnosis when FISH or RT-PCR fail to detect EWSR1-rearrangements. Any molecular findings should always be interpreted in relation to the specific clinical and pathological context.     

SARS CoV-2 infections in healthcare workers with a pre-existing T-cell response: a prospective cohort study

ObjectiveT-cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are observed in unexposed individuals. We evaluated the impact of this pre-existing cellular response on incident SARS-CoV-2 infections.MethodsThis was a follow-up study of 38 seronegative healthcare workers (HCWs) with previous evaluation of CD8+ and CD4+ T-cell responses after stimulation with SARS-CoV-2 structural proteins. Infection was considered in the presence of a positive RT-PCR test and/or confirmed seroconversion.ResultsTwenty of the 38 HCWs included (53%) had a previous specific CD8+ T-cell response to peptides encompassing the spike protein (S) in 13 (34%), the membrane (M) in 17 (45%), or/and the nucleocapsid (N) in three (8%). During a follow-up of 189 days (interquartile range (IQR) 172–195), 11 HCWs (29%) had an RT-PCR-positive test (n = 9) or seroconverted (n = 2). Median duration of symptoms was 2 days (IQR 0–7), and time to negative RT-PCR was 9 days (IQR 4–10). Notably, six incident infections (55%) occurred in HCWs with a pre-existing T-cell response (30% of those with a cellular response), who showed a significantly lower duration of symptoms (three were asymptomatic). Three of the six HCWs having a previous T-cell response continued to test seronegative. All the infected patients developed a robust T-cell response to different structural SARS-CoV-2 proteins, especially to protein S (91%).ConclusionA pre-existing T-cell response does not seem to reduce incident SARS-CoV-2 infections, but it may contribute to asymptomatic or mild disease, rapid viral clearance and differences in seroconversion.     

Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients

ObjectivesExhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its usefulness in the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia Aspergillus enzyme-linked immunosorbent assay was investigated.MethodsProspective, cross-sectional study of lung transplant recipient and haemotologic malignancy patients at a university centre. EBC samples were compared to concomitant bronchoalveolar lavage (BAL) samples among lung transplant recipients and healthy controls. EBC was collected over 10 minutes using a refrigerated condenser according to the European Respiratory Society/American Thoracic Society recommendations, with the BAL performed immediately thereafter.ResultsA total of 476 EBC specimens with 444 matched BAL specimens collected from lung transplant recipients (n = 197) or haemotologic malignancy patients (n = 133) were examined. Both diluted and untreated EBC optical density (OD) values (0.0830, interquartile range (IQR) 0.0680–0.1040; and 0.1130, IQR 0.0940–0.1383), respectively, from all patients regardless of clinical syndrome were significantly higher than OD values in healthy control EBCs (0.0508, IQR 0.0597–0.0652; p < 0.0001). However, the OD index values did not correlate with the diagnosis of IA (44 samples were associated with IA). Furthermore, no significant correlation was found between EBC GM and the matched BAL specimen.ConclusionsGM is detectable in EBC; however, no correlation between OD index values and IA was noted in lung transplant recipients.     

Machine learning for clinical decision support in infectious diseases: a narrative review of current applications

BackgroundMachine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID).ObjectivesWe aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID.SourcesReferences for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019.ContentWe found 60 unique ML-clinical decision support systems (ML-CDSS) aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n = 24, 40%), ID consultation (n = 15, 25%), medical or surgical wards (n = 13, 20%), emergency department (n = 4, 7%), primary care (n = 3, 5%) and antimicrobial stewardship (n = 1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%).ImplicationsConsidering comprehensive patient data from socioeconomically diverse healthcare settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for clinicians and patients.     

High prevalence of Pseudomonas aeruginosa carriage in residents of French and German long-term care facilities

ObjectivesTo determine prevalence, incidence, and factors associated with Pseudomonas aeruginosa (PA) intestinal carriage in residents of long-term care facilities (LTCFs) and to understand the population structure of this pathogen in LTCFs from two European countries.MethodsWe assessed the prevalence of PA intestinal carriage and the incidence of acquisition by collecting fecal samples from 403 residents of 20 LTCFs. We collected 289 environmental samples from sinks and drinking water. Factors associated with carriage and acquisition of intestinal PA were identified. All PA isolates had their antibiotic phenotypic resistance profile determined and their genome sequenced, from which we assessed the population structure of the collection and identified resistance determinants.ResultsWe found a high proportion of residents with PA intestinal carriage (51.6%) over the entire study period. Over the follow-up period, 28.6% of the residents acquired intestinal PA. Older age (OR, 1.29; 95% CI, 1.09–1.52; p = 0.002), urinary incontinence (OR, 2.56; 95% CI, 1.37–4.88; p = 0.003), and male sex (OR, 2.55; 95% CI, 1.05–6.18; p = 0.039) were associated with higher probability of carriage. Wheelchair usage (OR, 4.56; 95% CI, 1.38–15.05; p = 0.013) and a body mass index >25 (OR, 3.71; 95% CI, 1.17–11.82; p = 0.026) were associated with higher risk of PA acquisition. Population structure of our isolates was mainly non-clonal with 112 different STs among the 241 isolates. Most represented STs were high risk clones ST253 (n = 26), ST17 (n = 11), ST244 (n = 11), ST309 (n = 10), and ST395 (n = 10). Most PA isolates (86.3%) were susceptible to antibiotics, with no acquired genes conferring resistance to antipseudomonal agents.DiscussionWe found an unexpected high prevalence of PA intestinal carriage in LTCF residents mainly associated with individual-level factors. Our study revealed a polyclonal PA population structure suggesting that individual acquisition is more frequent than resident-to-resident transmission.     

Impact of Tele-nursing on adherence to treatment plan in discharged patients after coronary artery bypass graft surgery: A quasi-experimental study in Iran

Background and aimsCoronary artery bypass graft is a major surgery and has complications that require professional and long term follow-up and nursing care that if do not properly handled, could reduce the quality of life and increase post-operative complications. On the other hand Tele-nursing is a cost-effective way to educate and follow-up of patients. This study aimed to assess the impact of Tele-nursing on adherence to treatment plan in discharged patients after coronary artery bypass graft.Materials and methodsA quasi-experimental study was carried out at Ekbatan Therapeutic and Educational Center of Hamadan University of Medical Sciences at Hamadan, Iran, in 2013. In this study, 71 patients who had undergone coronary artery bypass graft surgery and had inclusion criteria were randomly divided into two experimental group (n = 36), and control group (n = 35). They completed questionnaire before discharging from Therapeutic and Educational Center. In the experimental group on days 2, 4, 7, second week (day 11), third week (day 18) and fourth week (day 25) after discharge, follow-up interventions and nursing education with Tele-nursing was done, but in the in the control groups, patients received only routine interventions. After completion of the intervention period, both groups completed the questionnaire and the results were compared.ResultsAdherence of treatment plan in both groups did not have significant difference before intervention (P = 0.696), but had a significant difference with regard to baseline after intervention in aromatherapy group (P <  0.01) and with control group after intervention (P < 0.01). Adherence to treatment plan in the aromatherapy group was better in compared to control group (P < 0.01).ConclusionTele-nursing is a convenient way, cost effective training and follow-up care for patients after coronary artery bypass surgery, which can improve patients’ adherence to treatment plan in developing countries such as Iran.     

Long-term follow-up for incident cirrhosis among pediatric cancer survivors with hepatitis C virus infection

BackgroundPediatric cancer patients who received blood transfusions were potentially exposed to hepatitis C virus (HCV) prior to second-generation HCV screening of blood products in 1992. Limited evidence is available about long-term incident cirrhosis in this population.ObjectivesWe aimed to estimate the overall and sex-specific incidence of cirrhosis among HCV-seropositive survivors of pediatric cancer.Study designWe identified 113HCV-seropositive pediatric cancer patients treated at St. Jude Children’s Research Hospital between 1962 and 1997, who survived ≥5 years post-diagnosis, and were followed through 2014. Our outcome was cirrhosis determined by liver biopsy or diagnostic imaging. We used a competing-risk framework to estimate the overall and sex-specific cumulative incidence and 95% confidence limits (CL) of cirrhosis at 10-year follow-up intervals.ResultsThe median duration of follow-up was 30 years (interquartile range = 28–36) post-cancer diagnosis. Cumulative incidence of cirrhosis increased at each 10-year interval from 0% after 10 years to 13% after 40 years (P_trend < 0.001). The median age at diagnosis of cirrhosis was 30 years (interquartile range = 24–38). We observed a linear trend in incidence for males (P_trend < 0.001), with a cumulative incidence of 18% (95% CL: 6.1%, 34%) after 40 years. The cumulative incidence for females was 6.5% (95% CL: 0.42%, 26%) after 40 years, but we did not observe a linear trend (P_trend = 0.99).ConclusionOur results suggest that the incidence of cirrhosis is similar between HCV-seropositive pediatric cancer survivors and the general population given similar duration of follow-up, but survivors may be diagnosed with cirrhosis at an earlier age.     

Quantitative histology as a diagnostic tool for celiac disease in children and adolescents

ObjectiveTo measure the villous height, the crypt depth, and the number of intraepithelial lymphocytes/100 enterocytes of the small intestinal mucosa of children and adolescents with celiac disease; and to classify these findings according to Q- Marsh and Q-histology scales.MethodsRetrospective study of a database from the Department of Pathology of biopsies from the second portion of the duodenum of pediatric patients. According to the histological report, three groups were established: celiac disease at diagnosis (n = 50), controls (n = 26), giardiasis (n = 10). In each biopsy, software (cellSens and Image J) evaluated 5 villous heights, 5 crypt depth and the number of intraepithelial lymphocytes/100 enterocytes.ResultsThe celiac group had the lowest mean villous height (197.83 μm) of all three groups (control = 477.70 μm; giardiasis = 397.04 μm. The celiac group's villous:crypt ratio (0.78) was significantly lower than the control group (1.89). The number of intraepithelial lymphocytes ≥25 was exclusive to the celiac group, with a sensitivity and specificity of 100 %. Only celiac patients were included in types 2 and 3 of the Q-histology classification.ConclusionCeliac disease patients showed shorter villous height than other groups, and the number of intraepithelial lymphocytes ≥25 was the best parameter to differentiate celiac from controls and giardiasis groups. Intraepithelial lymphocytes ≥25/100 enterocytes associated with any degree of villous atrophy, the classic Marsh 3 type, set the histological parameters of celiac disease. Quantitative histology is a valuable tool for diagnosing celiac disease, enabling histological changes in a short time, and the Q-histology scale appears to be more suitable than the Q-Marsh scale.     

Clinical characteristics and factors associated with hospital admission or death in 43 103 adult outpatients with coronavirus disease 2019 managed with the Covidom telesurveillance solution: a prospective cohort study

ObjectivesStudies on coronavirus disease 2019 (COVID-19) have mainly focused on hospitalized patients or those with severe disease. We aim to assess the clinical characteristics, outcomes and factors associated with hospital admission or death in adult outpatients with COVID-19.MethodsThis is a prospective cohort of outpatients with suspected or confirmed COVID-19, registered in the Covidom telesurveillance solution for home monitoring of patients with COVID-19 in the Greater Paris area, from March to August 2020. The primary outcome was clinical worsening, defined as hospitalization or death within 1 month after symptom onset.ResultsAmong 43 103 patients, mean age was 42.9 years (SD 14.3 years); 93.0% (n = 40 081) of patients were <65 years old and 61.9% (n = 26 688) were women. Of these 43 103 patients, 67.5% (n = 29 104) completed a medical questionnaire on co-morbidities and symptoms. The main reported co-morbidities were asthma (12.8%; n = 3685), hypertension (12.3%; n = 3546) and diabetes (4.8%; n = 1385). A small proportion of all eligible patients (4.1%, 95% CI 3.9–4.2; 1751/43 103) experienced clinical worsening. The rate of hospitalization was 4.0% (95% CI 3.8%–4.2%; n = 1728) and 0.1% (95% CI 0.1%–0.2%; n = 64) died. Factors associated with clinical worsening were male sex, older age, obesity and co-morbidities such as chronic renal disease or cancer under treatment. Probability of worsening was reduced with anosmia/ageusia.ConclusionsClinical worsening was rare among outpatients. Male sex, older age and co-morbidities such as chronic renal disease, active cancers or obesity were independently associated with clinical worsening. However, our cohort may include patients younger and healthier than the general population.     

Presence of pldA and exoU in mucoid Pseudomonas aeruginosa is associated with high risk of exacerbations in non–cystic fibrosis bronchiectasis patients

ObjectivesTo explore the association between the virulence genes exoU and pldA in isolated mucoid Pseudomonas aeruginosa and the clinical outcomes of patients with non–cystic fibrosis (CF) bronchiectasis.MethodsA prospective observational cohort study was performed in the Shanghai Pulmonary Hospital from October 2012 to January 2015. We consecutively enrolled all non-CF bronchiectasis patients with mucoid P. aeruginosa isolates obtained from bronchoalveolar lavage fluid or sputum. The exposure variable was the presence of virulence gene, exoU or pldA, in the strains. The primary outcome was exacerbation of bronchiectasis. Logistic regression analysis was performed to evaluate the association between virulence genes and exacerbation.ResultsThe final analysis included 147 patients (mean (SD) age, 57.86 (11.43) years, 101 female subjects) with median (interquartile range) follow-up of 18 (13–26) months. The following factors were relative to exacerbations: body mass index ≤18.5 kg/m² (odds ratio (OR) = 5.05; 95% confidence interval (CI), 1.37–18.57), length of stay ≥8 days (OR = 2.65; 95% CI, 1.14–6.19) and positive for either virulence gene (OR = 6.80; 95% CI, 1.47–31.37). The gene-positive group had more exacerbations per year (mean 2.37, SD 2.10, n = 33 vs. mean 0.79, SD 0.83, n = 114) and a higher proportion of patients with exacerbation (31/33, 93.94% vs. 74/114, 64.91%). The proportion of patients being exoU or pldA positive increased as the exacerbation frequency of bronchiectasis increased.ConclusionsThe virulence genes exoU and pldA in mucoid P. aeruginosa are significant risk factors for exacerbations in patients with non-CF bronchiectasis.