Characteristics and outcomes of ambulatory patients with suspected COVID-19 at a respiratory referral center.

RATIONALE: SARS-CoV-2 continues to cause a global pandemic and management of COVID-19 in outpatient settings remains challenging. OBJECTIVE: We sought to describe characteristics of patients with chronic respiratory disease (CRD) experiencing symptoms consistent with COVID-19, who were seen in a novel Acute Respiratory Clinic, prior to widely available testing, emergence of variants, COVID-19 vaccination, and post-vaccination (breakthrough) SARS-CoV-2 infections. METHODS: Retrospective electronic medical record data were analyzed from 907 adults with presumed COVID-19 seen between March 16, 2020 and January 7, 2021. Data included demographics, comorbidities, medications, vital signs, laboratory tests, pulmonary function tests, patient disposition, and co-infections. The overdispersed data (aod) R package was used to create a logit model using COVID-19 diagnosis by PCR as the dichotomous outcome variable. Univariate, conventional multivariate and elastic net machine learning were used to analyze data. RESULTS: Male gender, elevated baseline temperature, and respiratory rate predicted COVID-19 diagnosis. Eosinopenia, neutrophilia, and lymphocytosis were also associated with COVID-19 diagnosis. However, asthma and COPD diagnoses were not associated with SARS-CoV-2 PCR positive test. Male gender, low oxygen saturation, and lower forced expiratory volume in 1 s (FEV1) were associated with higher hospital referral. CONCLUSIONS: CRD patients with acute respiratory symptoms in the ambulatory setting were more likely to have COVID-19 if male, febrile and tachypneic. Patients with lower pre-morbid FEV1 and lower SPO2 are more likely to be referred to the hospital. A composite of vitals sigs and WBC differential help risk stratify CRD patients seeking care for presumed COVID-19.

Characteristics of Post-ICU and Post-COVID Recovery Clinics in 29 U.S. Health Systems.

The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%; physical, 69%; and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

Numerical simulation of pressure waves in the cochlea induced by a microwave pulse.

The pressure waves developing at the cochlea by the irradiation of the body with a plane wave microwave pulse are obtained by numerical simulation, employing a two-step finite-difference time-domain (FDTD) algorithm. First, the specific absorption rate (SAR) distribution is obtained by solving the Maxwell equations on a FDTD grid. Second, the temperature rise due to this SAR distribution is used to formulate the thermoelastic equations of motion, which are discretized and solved by the FDTD method. The calculations are performed for anatomically based full body human models, as well as for a head model. The dependence of the pressure amplitude at the cochlea on the frequency, the direction of propagation, and the polarization of the incident electromagnetic radiation, as well as on the pulse width, was investigated.

Presence of platelet antibodies in idiopathic thrombocytopenic purpura may discriminate acute from chronic disease.

UNLABELLED: This study estimated the prevalence of serum antibodies against thrombocyte glycoproteins, at disease onset (54 patients) and later on during the course of the disease (71 patients), in sera from children with idiopathic thrombocytopenic purpura (ITP). Only a minority had serum antibodies at disease onset, with a significantly higher frequency in those who developed the acute form of the disease than in those who developed the chronic form. Serum antibodies may persist after spontaneous cure of acute disease. There was no switch from immunoglobulin M (IgM) to IgG antibodies over time. CONCLUSION: The pathogenesis of the acute and chronic forms of ITP may be different.

Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice.

To address the role of neutrophil elastase in pulmonary emphysema, neutrophil elastase-deficient mice and wild-type littermate controls were exposed to long-term cigarette smoke. Compared to wild-type littermates, mice that were deficient in neutrophil elastase were significantly protected (59%) from the development of emphysema. Previously, we demonstrated complete protection from emphysema in the absence of macrophage elastase. Further analysis revealed several interactions between these two elastases. Each elastase inactivated the endogenous inhibitor of the other, with neutrophil elastase degrading tissue inhibitor of metalloproteinase-1, and macrophage elastase degrading alpha-1-antitrypsin. Cigarette smoke-induced recruitment of both neutrophils and monocytes was impaired in the absence of neutrophil elastase. Moreover, there was less macrophage elastase activity secondary to decreased macrophage accumulation in neutrophil elastase-deficient mice. This study demonstrates a direct role for neutrophil elastase in emphysema and highlights the interdependence of the proteinases and inflammatory cells that mediate lung destruction in response to cigarette smoke.

Diagnostic assessment of haemorrhagic rash and fever.

AIMS: To establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes for haemorrhagic rashes accompanied by fever. METHODS: In a prospective study, 264 infants and children hospitalised with fever and skin haemorrhages were studied. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables distinguished between meningococcal disease and other conditions on admission: (1) skin haemorrhages of characteristic appearance; (2) universal distribution of skin haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than 2 mm; (4) poor general condition (using a standardised observation scheme); and (5) nuchal rigidity. If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

[Prednisolone treatment of respiratory syncytial virus infection. A randomized, controlled trial of 147 children]. / Prednisolonbehandling af respiratorisk syncytial virusinfektion. En randomiseret, kontrolleret undersøgelse af 147 børn.

OBJECTS: Our objective was to evaluate the effect of systemic prednisolone as an adjunct to conventional treatment with beta 2-agonist, fluid replacement and respiratory support in hospitalized infants younger than 24 months with respiratory syncytial virus (RSV) infection. METHODS: The study was randomized, double-blind and placebo-controlled. During the winter of 1995-96, 147 infants less than two years of age hospitalized with RSV infection were allocated to treatment with either systemic prednisolone mixture 2 mg/kg daily or placebo for 5 days. RESULTS: Our main outcome measures were: 1. Acute effect variables: duration of stay in hospital, use of medicine and supportive measures while in hospital. 2. At follow-up one month after discharge: duration of illness, start in day care center, morbidity and use of medicine. 3. At follow-up one year after discharge: morbidity, use of medicine and skin prick tests with allergens. CONCLUSION: Prednisolone treatment had no effect on any of the outcome measures. We find our results in agreement with the largest studies reported earlier; therefore, corticosteroid, whether by systemic route or by inhalation, should not be prescribed to infants with RSV infection.

Prednisolone treatment of respiratory syncytial virus infection: a randomized controlled trial of 147 infants.

OBJECTIVE: To evaluate the effect of systemic prednisolone as an adjunct to conventional treatment with beta2-agonist, respiratory support, and fluid replacement in hospitalized infants <24 months of age with respiratory syncytial virus (RSV) infection. METHODS: The study was randomized, double-blind, and placebo-controlled. During the winter of 1995-1996, 147 infants <2 years of age, hospitalized with RSV infection, were allocated to treatment with either systemic prednisolone mixture 2 mg/kg daily or placebo for 5 days. MAIN OUTCOME MEASURES: The acute effect variables were duration of stay in hospital, use of medicine, and supportive measures while in hospital. At follow-up 1 month after discharge, the acute effect variables were duration of illness, start in day care center, morbidity, and use of medicine. At follow-up 1 year after discharge, the acute effect variables were morbidity, use of medicine, and skin prick tests with allergens. RESULTS: Prednisolone treatment had no effect on any of the outcome measures. CONCLUSIONS: Our randomized prospective study in infants hospitalized with acute RSV infection showed no effect of systemic prednisolone treatment either in the acute state of RSV infection, nor in the follow-up 1 month and 1 year after admission to hospital. We find our results in agreement with the largest studies reported earlier; therefore, corticosteroid, whether by the systemic route or by inhalation, should not be prescribed to infants with RSV infection.

Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions.

BACKGROUND: Investigations concerning the severity of respiratory syncytial virus (RSV) disease as related to (1) RSV type and genotype determined respectively by PCR and restriction enzyme analysis and (2) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) values in samples of nasopharyngeal secretion (NPS) have not been previously reported. METHODS: We prospectively studied 105 RSV infections in the lower respiratory tract of infants and young children admitted to a pediatric department in Copenhagen during three winter seasons, 1993, 1994 and 1995. RSV strains were typed and genotyped, respectively, by PCR and nucleic acid restriction analysis and correlated to the severity of the disease. The ratio IL-6:TNF-alpha, determined from IL-6- and TNF-alpha values in samples of NPS, was related to the severity of the disease. Concentrations of IL-6 and of TNF-alpha were determined in serum samples taken during 5 weeks after the onset of illness. RESULTS: Type B infections produced more severe disease than did type A infections, as assessed on the length of the hospital stay, use of respiratory support and the presence of an infiltrate on a chest radiograph. This difference was age-related. It was observed in infants 0 to 5 months old, but not in older age groups. Type B genotype B1122 produced more severe disease than type A genotype A2311 in infants 0 to 11 months old. Increased serum concentrations of IL-6 and TNF-alpha were detected in samples taken 1 to 2 days after the onset of illness. Whereas TNF-alpha serum concentrations remained high, IL-6 serum concentrations decreased during the following 3 to 4 weeks. The IL-6:TNF-alpha ratio in samples of NPS was related to the severity of the disease. A high ratio was related to a low severity. CONCLUSIONS: The severity of disease in patients admitted with acute RSV infections can be correlated to the RSV type as determined by PCR, to the RSV genotype as determined by nucleic acid restriction analysis and to the ratio IL-6:TNF-alpha in NPS.

Prospects for application of post-consumer used plastics in food packaging.

The two most widely used polymers in packaging in recent years are polyethylene terephthalate (PET) and polyethylene (PE). The biggest fractions of these polymers are not re-utilized, in spite of the fact that they possess excellent properties even after their first application. The ban on using recycled polymers in food packaging applications and the lack of good value outlets for these materials causes them to end up in landfills. The high cost nylon, used in packaging primarily as high gas barrier laminates with PE, also finds its way to landfills. In this case, the reason is the difficulty of recycling different polymers that are incompatible. Thus, the Municipal Solid Waste (MSW) stream transferred to landfills contains many plastic packages. These packages are being blamed as a major pollutant of the environment in spite of the fact that all plastics contribute only a small percentage to the weight of the garbage in landfills. If proper and cost effective applications for the recycled polymers could be developed, the waste related to their disposal could be limited. In addition, the contribution of plastic packages to the environmental problem could be diminished. In the present paper, the possibility of sandwiching a contaminated PET layer between two layers of the virgin material was studied. The aim of the study was to determine whether such an operation could lower the migration level of contaminants from a multilayer structure (containing a recycled layer of PET) to values below the limits required by regulatory agencies. The diffusion coefficients (required to determine migration) of four organic liquids in PET were determined. As a result of the sandwiching operation, the amount of pollutant (toluene) migrating into the food simulant was reduced by two orders of magnitude. The properties of PE/nylon blends were also studied. It was found that the high gas barrier properties of nylon are preserved in the blend when proper processing conditions are used. Therefore, the recycled material could be used as a centre layer in a multilayer structure providing good gas barrier properties to this structure.

Restriction pattern variability of respiratory syncytial virus during three consecutive epidemics in Denmark.

A PCR-based assay was used to distinguish between respiratory syncytial virus (RSV) group A and B in order to analyze their prevalence in Denmark in three consecutive epidemics during the winters of 1992/93, 1993/94 and 1994/95. A total of 96 RSV strains isolated from hospitalized children were examined, showing alternation of group prevalence. Furthermore, the genetic variability of the RSV isolates was illustrated by restriction enzyme analysis of PCR products originating from a part of the F and G proteins that has been reported to be highly variable. We found that, in general, different genome types predominated each year, some types being present in consecutive epidemics, indicating a contribution of strains circulating unattended between outbreak seasons, while others seemed to disappear or became undetectable, being replaced by emerging types. Some of the genome types found seemed related to strains isolated up to more than two decades ago in other parts of the world. This indicates that the temporal fluctuation in predominance of genome types presumably caused by selective pressure exerted by host immunity is due to the favoring of strains from a pool of globally circulating, genetically relatively stable genome types, rather than a molecular evolution in strains induced or directed by immunoselective pressure.

Prolonged extreme thrombocytosis associated with neurofibromatosis type 1.

A girl with neurofibromatosis type 1 showed in infancy extreme thrombocytosis with platelet counts exceeding 2000 x 10(9)/L. Platelet counts remained elevated the first 4 years of life. A large deletion located at chromosome 17q11 was observed. The transient thrombocythemia may relate to a regulator of megakaryocytopoiesis located in the vicinity of the NF1 gene or to the excessive risk of chronic myelomonocytic leukemia in neurofibromatosis.

Long-term survival and nutritional data in patients with cystic fibrosis treated in a Danish centre.

BACKGROUND: Adequate nutrition and optimal treatment of bronchopulmonary infections are both of critical importance in maintaining the health of patients with cystic fibrosis. The cystic fibrosis centre in Copenhagen has followed a regimen of very early and aggressive antimicrobial treatment, especially against Pseudomonas aeruginosa infection. An unrestricted diet of low fat and high protein without hyperalimentation was recommended before 1985 which was then changed to a high fat, high calorie intake. METHODS: The overall impact of the treatment regimen was evaluated by a cross sectional analysis of all 223 patients who attended the centre in 1989. Growth and nutritional parameters were combined with lung function parameters and with a retrospective analysis of chronic P aeruginosa infection and its duration. Survival curves for all 313 patients treated at the centre since 1949 were calculated. RESULTS: All the patients with cystic fibrosis had normal height, although the final height was achieved a little later than in healthy controls. Body weight was lower than normal in males above 15 and in females above 10 years of age. The body mass index (BMI), which was approximately 98% of normal in the younger patients, declined to 90% in adult men and to 83% in adult women with cystic fibrosis, and was strongly correlated with lung function parameters. In 1989 the median age of survival of all patients treated in the centre since 1949 was 30 years (32 years in males and 29 years in females). CONCLUSIONS: The overall treatment regimen in the cystic fibrosis centre in Copenhagen is associated with growth and survival rates that are at least equal to those in other cystic fibrosis centres in other countries.

Elevated vibration perception threshold in young patients with type 1 diabetes in comparison to non-diabetic children and adolescents.

The vibration perception threshold (VPT) was investigated by biothesiometry in 61 children (28 boys) with Type 1 diabetes, mean age 15.5 (range 10-21) years, duration of diabetes 6.9 (range 1-19) years, and in 76 healthy children (39 males), mean age 13.8 (range 10-19) years. The measurements were performed in triplicate on the right second finger and on the right first toe. The vibration perception threshold was significantly increased (p < 0.0001) in the young diabetic patients (mean +/- SD, finger 4.1 +/- 1.1 V, toe: 5.7 +/- 1.3 V) compared to healthy children (finger 3.4 +/- 0.9 V, toe: 3.6 +/- 1.3 V). Twenty percent of adolescents with Type 1 diabetes had a VPT above the 95th percentiles (finger: 5 V, toe 6.5 V) for normal control children. In healthy controls a significant correlation (r = 0.27, p < 0.01) was found for VPT in finger versus toe. This relationship was not significant in the diabetic group and may be due to reduced sensitivity of the fingertips caused by frequent blood glucose testing. Age, Tanner stage and height were significantly correlated to VPT (toe) in both diabetic and normal boys, while duration of diabetes, HbA1c, arterial blood-pressure and body mass index were not significantly associated with VPT in any of the groups. The results indicate that changes in VPT appears early in childhood and emphasize a need for further studies of subclinical neuropathy in young patients with Type 1 diabetes.

beta-lactamases in Shigella.

The occurrence of resistance and production of beta-lactamases was investigated in 60 Shigella strains. Ampicillin resistance was found in 28 (47%) of the isolates, the resistance being more frequent in Sh. flexneri than in Sh. sonnei. All strains were susceptible to cefotaxime, mecillinam, and ciprofloxacin. The beta-lactamases produced by Shigella were similar to TEM-1, OXA-1, or the low-level chromosomally mediated cephalosporinase produced by Escherichia coli. The beta-lactamases produced by Sh. flexneri were most often the OXA-1-like enzymes.

Screening method for beta-lactamase substrate profiles.

A disc diffusion method, based on the idea of Klundert, for screening of substrate profiles of beta-lactamases was developed in order to perform epidemiological studies. The method was tested against 30 different reference beta-lactamases and 59 clinical isolates known to produce TEM-1, SHV-1 and BRO-1. The reproducibility and discriminating power of the disc diffusion method made it possible to differentiate between eight types of substrate profiles for the 30 reference beta-lactamases and to differentiate between TEM-1, SHV-1 and BRO-1 from clinical isolates. In combination with analytical isoelectric focusing the disc diffusion method gives a reliable identification of beta-lactamases.

Should aerobic blood cultures be shaken intermittently or continuously?

Stationary incubation of aerobic blood cultures was compared with intermittent shaking in aerobic Vacutainer 2630 bottles with agar slants during the first 24 h, and was simultaneously compared with the continuously shaken aerobic Bactec 6A bottles as a reference system. Intermittent shaking did not significantly increase or decrease the seven days yield of the Vacutainer bottles as compared with the continuously agitated Bactec 6A bottles. When one of 604 paired Vacutainer bottles was agitated for eight h and the other incubated stationary, the speed of growth detection was significantly greater in the agitated bottle (p less than 0.001), but significantly less than with continuously agitated Bactec 6A bottles (p less than 0.001). Agitation for 14 h showed the same pattern of detection speed. These results suggest that it is desirable initially to agitate aerobic blood cultures either intermittently or continuously.