Optimal symptom combinations to aid COVID-19 case identification: Analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Optimal symptom combinations to aid COVID-19 case identification: analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Partnerships in primary health care. A process for re-visioning nursing education.

This article describes the process of curriculum change in a baccalaureate nursing program and the design of a competency-oriented learning system in primary health care, community-focused nursing education.

Control of ventilation in the hypercapnic skate Raja ocellata: I. Blood and extradural fluid.

In order to study the role of CO2 and acid-base status in contributing to ventilatory drive, skate were exposed to normoxic hypercapnia (PICO2 = 7.5 Torr) under conditions where the primary O2 drive would remain unaltered. Blood O2 transport was markedly insensitive to CO2, with no Root effect and only a small Bohr effect. Red blood cell pHi was not preferentially regulated, and there was no evidence of RBC swelling or nucleoside triphosphate adjustment. Although there were no changes in arterial O2 levels during hypercapnia, ventilation immediately increased 2.7-fold through large changes in stroke volume and small changes in frequency, and declined only slightly through 24-48 h. PaCO2 equilibrated rapidly with PICO2, driving down arterial pHa, which was 65% corrected through HCO3- accumulation by 24 h. In contrast, the extradural fluid outside the brain equilibrated only very slowly, and was clearly not involved in the ventilatory stimulation. Increased ventilation during hypercapnia may be related to depression in pHa.

Control of ventilation in the hypercapnic skate Raja ocellata: II. Cerebrospinal fluid and intracellular pH in the brain and other tissues.

This study examined the possible role(s) of central acid-base stimuli in the increase in ventilation induced by hypercapnia in the skate, a response that is not due to an O2 signal (Graham et al., Respir. Physiol., 1990, 80: 251-270). Skate were sampled for cerebrospinal fluid (CSF) acid-base status, intracellular pH of the brain (14C-DMO method), and pHi in other tissues throughout 24 h of exposure to PICO2 = 7.5 Torr. CSF PCO2 rapidly equilibrated with the elevated PaCO2. Despite the much lower non-HCO3- buffer capacity in the CSF, CSF pH was not depressed to the same extent as blood pHa. CSF pH was also regulated rapidly, returning to control levels by 8-10 h, whereas pHa remained significantly depressed at 24 h. Similarly, the pHis of the weakly buffered brain and heart ventricle were initially compensated more rapidly than those of more strongly buffered white muscle and red blood cells. However, brain pHi adjustment slowed markedly after 4 h and stabilized at only 70% compensation by 20-24 h, suggesting that brain intracellular acidosis may play a role in the long-term increase in ventilation. CSF and brain were the only compartments which did not exhibit an apparent compounding metabolic acidosis during the initial stages of hypercapnic exposure. While these results illustrate the primacy of central acid-base regulation, they do not support a role for CSF pH in the long-term elevation of ventilation in response to hypercapnia. Depressions in pHa and brain pHi appear the two most likely candidates for proximate stimuli.

Phoneme-specific nasal emission in children with and without physical anomalies of the velopharyngeal mechanism.

Phoneme-specific nasal emission was identified in 36 children ranging in age from 3 years, 3 months to 16 years, 5 months; 19 children had no physical anomalies of the orofacial mechanism, whereas 17 had findings ranging from minor to severe. Five patterns of phoneme-specific nasal emission were exhibited by 2 or more children. An additional eight patterns were exhibited by 1 child each. Sibilants were clearly the most frequently affected phonemes. There was no significant correlation between the number of phonemes affected by nasal emission and the number of phonologic processes exhibited by the children in either subject group. The two subject groups were more alike than different in the speech behaviors observed, underscoring a fundamental homogeneity among speakers who exhibit phoneme-specific nasal emission.

High concentrations of methemoglobin in five species of temperate marine teleosts.

Blood samples from five species of marine teleosts were assayed for methemoglobin (metHb) levels during winter and summer acclimatization. There was at least 7% total hemoglobin in the met-form in all species, and as high as 27% in one species, the Atlantic cod (Gadus morhua). There was significant seasonal variation in metHb levels for three of the five species, the highest values occurring during the winter months; cunners (Tautogolabrus adspersus) 15.6% in winter and 10.1% in the summer, shorthorn sculpin (Myoxocephalus scorpius) 20.0% in the winter and 8.19% in the summer, longhorn sculpin (Myoxocephalus octodecemspinosus) 17.3-21.6% in the winter and 8.12% in the summer. The winter flounder (Pseudopleuronectes americanus) and the Atlantic cod maintained metHb concentrations constant throughout the year: 13% and 27%, respectively. There does not appear to be any relationship between the activity of a fish and the level of metHb in its blood.

Blood viscosity in arctic fishes.

The blood viscosity of arctic char, Salvelinus alpinus, and shorthorn sculpin, Myoxocephalus scorpius, from the arctic (74 degrees 42'N) was measured with a cone-plate viscometer. Blood viscosity of the two arctic species was considerably lower, less shear rate dependent, and less temperature dependent than the blood of winter flounder (Pseudopleuronectes americanus) from more temperate waters. The rheological properties of the arctic fish blood would minimize blood flow resistance and thus be advantageous at the low temperatures (0 degree C) characterizing their environment.

Hematology of three deep-sea fishes: a reflection of low metabolic rates.

Blood was collected from three species of fish, Antimora rostrata (Moridae), Lycodes esmarkii (Zoarcidae), Macrurus berglax (Macrouridae), caught at depths ranging from 280 to 2300 m. Hemoglobin concentrations were low in all three species, ranging from 4.4 to 5.4 g/100 ml. Mean erythrocyte volumes were relatively large, and ranged from 277 micron3 in M. berglax to 672 micron3 in A. rostrata. Blood oxygen dissociation curves were hyperbolic, with relatively low Hill constants (0.95-1.26). Mean P50 values ranged from 10 mmHg in M. berglax to 28 mmHg in L. esmarkii. It is concluded that the hematology and oxygen-binding characteristics of the blood of these three deep-sea fish reflects adaptations to low metabolic rates and low general activity habits.

Acute lymphocytic leukemic transformation of chronic lymphocytic leukemia: substantiation by flow cytometry.

Acute leukemia, during the course of chronic lymphocytic leukemia, is a rare event and only a small fraction of such cases have been shown to be true transformations to acute lymphocytic leukemia. In one previous case, evidence suggested this was transformation of a single neoplastic clone. The present report describes the clinical and laboratory findings in a case of chronic lymphocytic leukemia in which an acute leukemic pattern evolved. The fluorescence-activated cell sorter provided the resolution needed to distinguish low numbers of surface immunoglobulins on the acute leukemic cells, verifying their identity as B lymphoblasts. Furthermore, a small population of large cells bearing the same light chain type as the acute leukemia cells were detected in the spleen 3 1/2 months before clinical or laboratory evidence of the onset of the acute leukemia.