Long-term functioning status of COVID-19 survivors: a prospective observational evaluation of a cohort of patients surviving hospitalisation.

OBJECTIVES: The study investigated the long-term functional status of hospitalised COVID-19 survivors to explore and document their functional situation. DESIGN: This prospective observational study assessed 801 COVID-19 survivors at 3-11 months after hospital discharge. It analyses participants' sociodemographic background, COVID-19 clinical manifestations, and clinical and functional evaluations. SETTING: Tertiary-level university hospital in São Paulo, Brazil. PARTICIPANTS: Study participants are COVID-19 survivors admitted to hospital care for at least 24 hours to treat acute SARS-CoV-2 infection. OUTCOME MEASURES: Epworth Sleepiness Scale, EuroQoL-5 Dimensions-5 Levels, Functional Assessment of Chronic Illness Therapy-Fatigue, Functional Independence Measure, Functional Oral Intake Scale, Handgrip Strength, Insomnia Severity Index, Medical Research Council (MRC) Dyspnea Scale, MRC sum score, Modified Borg Dyspnea Scale, pain Visual Analogue Scale, Post-COVID-19 Functional Status, Timed Up and Go, WHO Disability Assessment Schedule 2.0, 1-Minute Sit to Stand Test. RESULTS: Many participants required invasive mechanical ventilation (41.57%, 333 of 801). Mean age was 55.35±14.58 years. With a mean of 6.56 (SD: 1.58; 95% CI: 6.45 to 6.67) months after hospital discharge, 70.86% (567 of 800) reported limited daily activities, which were severe in 5.62% (45 of 800). They also reported pain and discomfort (64.50%, 516 of 800), breathlessness (64.66%, 514 of 795), and anxiety and depression (57.27%, 457 of 798). Daytime sleepiness and insomnia evaluations showed subthreshold results. Most (92.85%, 727 of 783) participants reported unrestricted oral intake. Data indicated no generalised fatigue (mean score: 39.18, SD: 9.77; 95% CI: 38.50 to 39.86). Assessments showed poor handgrip strength (52.20%, 379 of 726) and abnormal Timed Up and Go results (mean 13.07 s, SD: 6.49). The invasive mechanical ventilation group seemed to have a better handgrip strength however. We found no clear trends of change in their functional status during months passed since hospital discharge. CONCLUSIONS: Muscle weakness, pain, anxiety, depression, breathlessness, reduced mobility, insomnia and daytime sleepiness were the most prevalent long-term conditions identified among previously hospitalised COVID-19 survivors.

Process mining for healthcare: Characteristics and challenges.

Process mining techniques can be used to analyse business processes using the data logged during their execution. These techniques are leveraged in a wide range of domains, including healthcare, where it focuses mainly on the analysis of diagnostic, treatment, and organisational processes. Despite the huge amount of data generated in hospitals by staff and machinery involved in healthcare processes, there is no evidence of a systematic uptake of process mining beyond targeted case studies in a research context. When developing and using process mining in healthcare, distinguishing characteristics of healthcare processes such as their variability and patient-centred focus require targeted attention. Against this background, the Process-Oriented Data Science in Healthcare Alliance has been established to propagate the research and application of techniques targeting the data-driven improvement of healthcare processes. This paper, an initiative of the alliance, presents the distinguishing characteristics of the healthcare domain that need to be considered to successfully use process mining, as well as open challenges that need to be addressed by the community in the future.

Oropouche virus cases identified in Ecuador using an optimised qRT-PCR informed by metagenomic sequencing.

Oropouche virus (OROV) is responsible for outbreaks of Oropouche fever in parts of South America. We recently identified and isolated OROV from a febrile Ecuadorian patient, however, a previously published qRT-PCR assay did not detect OROV in the patient sample. A primer mismatch to the Ecuadorian OROV lineage was identified from metagenomic sequencing data. We report the optimisation of an qRT-PCR assay for the Ecuadorian OROV lineage, which subsequently identified a further five cases in a cohort of 196 febrile patients. We isolated OROV via cell culture and developed an algorithmically-designed primer set for whole-genome amplification of the virus. Metagenomic sequencing of the patient samples provided OROV genome coverage ranging from 68-99%. The additional cases formed a single phylogenetic cluster together with the initial case. OROV should be considered as a differential diagnosis for Ecuadorian patients with febrile illness to avoid mis-diagnosis with other circulating pathogens.

Crack cocaine smoke on pregnant rats: Maternal evaluation and teratogenic effect.

This study aimed to evaluate maternal toxicity, teratogenic, and placental oxidative effects resulting from the exposure of rats to crack cocaine smoke during pregnancy. Pregnant rats were exposed either to the smoke of crack and ashes (Crack) or to the smoke of ashes alone, nonexposed or pair-fed with the Crack group. Crack group was exposed to the smoke resulting from the burning of 250 mg of crack for 10 min, twice a day, from 7 days prior to mating until cesarian on gestational day 20. Placental oxidative stress and classical parameters of maternal and fetal evaluation were studied, in addition to the morphometric analysis of the fetal metamers. Even in the absence of changes in body weight gain and feed intake, crack altered the reproductive performance of dams. Exposure to the drug promoted late closure of the fetal fontanel. Furthermore, the morphometric study of the brain mass (BM)/skull cap ratio revealed a decrease in the BM of the fetuses exposed to the drug. Exposure to crack has an oxidative potential in fetal development, since exposure to the drug promoted placental lipid peroxidation. Our study showed that daily exposure to crack, even in lower frequency than that performed by users, has a teratogenic potential.

Transcriptomics of atopy and atopic asthma in white blood cells from children and adolescents.

Early allergic sensitisation (atopy) is the first step in the development of allergic diseases such as atopic asthma later in life. Genes and pathways associated with atopy and atopic asthma in children and adolescents have not been well characterised.A transcriptome-wide association study (TWAS) of atopy and atopic asthma in white blood cells (WBCs) or whole blood was conducted in a cohort of 460 Puerto Ricans aged 9-20 years (EVA-PR study) and in a cohort of 250 Swedish adolescents (BAMSE study). Pathway enrichment and network analyses were conducted to further assess top findings, and classification models of atopy and atopic asthma were built using expression levels for the top differentially expressed genes (DEGs).In a meta-analysis of the study cohorts, both previously implicated genes (e.g. IL5RA and IL1RL1) and genes not previously reported in TWASs (novel) were significantly associated with atopy and/or atopic asthma. Top novel genes for atopy included SIGLEC8 (p=8.07×10-13), SLC29A1 (p=7.07×10-12) and SMPD3 (p=1.48×10-11). Expression quantitative trait locus analyses identified multiple asthma-relevant genotype-expression pairs, such as rs2255888/ALOX15 Pathway enrichment analysis uncovered 16 significantly enriched pathways at adjusted p<0.01, including those relevant to T-helper cell type 1 (Th1) and Th2 immune responses. Classification models built using the top DEGs and a few demographic/parental history variables accurately differentiated subjects with atopic asthma from nonatopic control subjects (area under the curve 0.84).We have identified genes and pathways for atopy and atopic asthma in children and adolescents, using transcriptome-wide data from WBCs and whole blood samples.

Isolation of Oropouche Virus from Febrile Patient, Ecuador.

We report identification of an Oropouche virus strain in a febrile patient from Ecuador by using metagenomic sequencing and real-time reverse transcription PCR. Virus was isolated from patient serum by using Vero cells. Phylogenetic analysis of the whole-genome sequence showed the virus to be similar to a strain from Peru.

White Matter Volume Predicts Language Development in Congenital Heart Disease.

OBJECTIVE: To determine whether brain volume is reduced at 1 year of age and whether these volumes are associated with neurodevelopment in biventricular congenital heart disease (CHD) repaired in infancy. STUDY DESIGN: Infants with biventricular CHD (n = 48) underwent brain magnetic resonance imaging (MRI) and neurodevelopmental testing with the Bayley Scales of Infant Development-II and the MacArthur-Bates Communicative Development Inventories at 1 year of age. A multitemplate based probabilistic segmentation algorithm was applied to volumetric MRI data. We compared volumes with those of 13 healthy control infants of comparable ages. In the group with CHD, we measured Spearman correlations between neurodevelopmental outcomes and the residuals from linear regression of the volumes on corrected chronological age at MRI and sex. RESULTS: Compared with controls, infants with CHD had reductions of 54 mL in total brain (P = .009), 40 mL in cerebral white matter (P <.001), and 1.2 mL in brainstem (P = .003) volumes. Within the group with CHD, brain volumes were not correlated with Bayley Scales of Infant Development-II scores but did correlate positively with MacArthur-Bates Communicative Development Inventory language development. CONCLUSIONS: Infants with biventricular CHD show total brain volume reductions at 1 year of age, driven by differences in cerebral white matter. White matter volume correlates with language development, but not broader developmental indices. These findings suggest that abnormalities in white matter development detected months after corrective heart surgery may contribute to language impairment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00006183.

Modelling Neglected Tropical Diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings.

BACKGROUND: The African Programme for Onchocerciasis Control has proposed provisional thresholds for the prevalence of microfilariae in humans and of L3 larvae in blackflies, below which mass drug administration (MDA) with ivermectin can be stopped and surveillance started. Skin snips are currently the gold standard test for detecting patent Onchocerca volvulus infection, and the World Health Organization recommends their use to monitor progress of treatment programmes (but not to verify elimination). However, if they are used (in transition and in parallel to Ov-16 serology), sampling protocols should be designed to demonstrate that programmatic goals have been reached. The sensitivity of skin snips is key to the design of such protocols. METHODS: We develop a mathematical model for the number of microfilariae in a skin snip and parameterise it using data from Guatemala, Venezuela, Ghana and Cameroon collected before the start of ivermectin treatment programmes. We use the model to estimate sensitivity as a function of time since last treatment, number of snips taken, microfilarial aggregation and female worm fertility after exposure to 10 annual rounds of ivermectin treatment. RESULTS: The sensitivity of the skin snip method increases with time after treatment, with most of the increase occurring between 0 and 5 years. One year after the last treatment, the sensitivity of two skin snips taken from an individual infected with a single fertile female worm is 31 % if there is no permanent effect of multiple ivermectin treatments on fertility; 18 % if there is a 7 % reduction per treatment, and 0.6 % if there is a 35 % reduction. At 5 years, the corresponding sensitivities are 76 %, 62 % and 4.7 %. The sensitivity improves significantly if 4 skin snips are taken: in the absence of a permanent effect of ivermectin, the sensitivity of 4 skin snips is 53 % 1 year and 94 % 5 years after the last treatment. CONCLUSIONS: Our model supports the timelines proposed by APOC for post-MDA follow-up and surveillance surveys every 3-5 years. Two skin snips from the iliac region have reasonable sensitivity to detect residual infection, but the sensitivity can be significantly improved by taking 4 snips. The costs and benefits of using four versus two snips should be evaluated.

Biliary drainage in patients with unresectable, malignant obstruction where ERCP fails: endoscopic ultrasonography-guided choledochoduodenostomy versus percutaneous drainage.

BACKGROUND: Endoscopic retrograde cholangiopancreatography may fail because of malignant involvement of the second portion of the duodenum and the major papilla. Alternatives include percutaneous transhepatic biliary drainage (PTBD) or surgical bypass. Endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CD) has been reported as an alternative. OBJECTIVE: To prospectively compare EUS-CD and PTBD in patients with unresectable malignant biliary obstruction. DESIGN: Prospective and randomized study. SETTING: Tertiary center. MAIN OUTCOME MEASUREMENTS: Success and efficacy comparison EUS-CD with PTBD. RESULTS: Twenty-five subjects were randomized (13 EUS-CD and 12 PTBD). Mean age was 67 years (SD, 11.9). The 2 groups were similar before intervention in terms of quality of life [EUS-CD (58.3) vs. PTBD (57.8); P=0.78], total bilirubin (16.4 vs. 17.2; P=0.7), alkaline phosphatase (539 vs. 518; P=0.7), and gamma-glutamyl transferase (554.3 vs. 743.5; P=0.56). All procedures were technically and clinically successful in both groups. At 7-day follow-up there was a significant reduction in total bilirubin in both the groups (EUS-CD, 16.4 to 3.3; P=0.002 and PTBD, 17.2 to 3.8; P=0.01), although no difference was noted comparing the 2 groups (EUS-CD to PTBD; 3.3 vs. 3.8; P=0.2). There was no difference between the complication rates in the 2 groups (P=0.44), EUS-CD (2/13; 15.3%) and PTBD (3/12; 25%). Costs were similar in the 2 groups also ($5673-EUS-CD vs. $7570-PTBD; P=0.39). LIMITATIONS: Small sample size and single center study. CONCLUSIONS: EUS-CD can be an effective and safe alternative to PTBD with similar success, complication rate, cost, and quality of life.

Density estimates of Panamanian owl monkeys (Aotus zonalis) in three habitat types.

The resolution of the ambiguity surrounding the taxonomy of Aotus means data on newly classified species are urgently needed for conservation efforts. We conducted a study on the Panamanian owl monkey (Aotus zonalis) between May and July 2008 at three localities in Chagres National Park, located east of the Panama Canal, using the line transect method to quantify abundance and distribution. Vegetation surveys were also conducted to provide a baseline quantification of the three habitat types. We observed 33 individuals within 16 groups in two out of the three sites. Population density was highest in Campo Chagres with 19.7 individuals/km(2) and intermediate densities of 14.3 individuals/km(2) were observed at Cerro Azul. In la Llana A. zonalis was not found to be present. The presence of A. zonalis in Chagres National Park, albeit at seemingly low abundance, is encouraging. A longer-term study will be necessary to validate the further abundance estimates gained in this pilot study in order to make conservation policy decisions.

In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

Influence of hyperthyroidism on lindane-induced hepatotoxicity in the rat.

Parameters related to hepatic oxidative stress, cell injury, phagocytic activity, and liver histology were studied in control rats and in animals subjected to L-3,3',5-triiodothyronine (T3) and/or lindane administration. Hyperthyroidism elicited a calorigenic response and increased rates of hepatic O2 uptake, which were not modified by lindane treatment. T3 diminished serum lindane levels as well as those in the liver and adipose tissue, whereas lindane enhanced serum T3 levels in animals given T3. Compared with control rats, lindane significantly increased the rate of formation of thiobarbituric acid reactants (TBARS) by the liver, with no changes in either the reduced glutathione (GSH) content, the TBARS/GSH ratio as indicator of oxidative stress, or in the fractional rates of lactate dehydrogenase (LDH) and GSH efflux from perfused livers as integrity parameters. Hyperthyroidism induced GSH depletion in the liver, with a significant enhancement in the TBARS formation, the TBARS/GSH ratio, and in the fractional LDH and GSH efflux. These parameters were increased further by joint T3 and lindane administration in a magnitude exceeding the sum of the effects produced by the separate treatments. In addition, hyperthyroidism led to Kupffer cell hyperplasia and significant increases in serum glutamate oxalacetate transaminase (GOT) and in hepatic zymosan-induced chemiluminescence, while liver myeloperoxidase (MPO) activity was found unchanged, compared with controls. Rats treated with lindane presented normal liver histology, with no changes in biochemical parameters related to cell injury. The joint administration of T3 and lindane, however, elicited a marked elevation in serum GOT and glutamate pyruvate transaminase (GPT), concomitantly with extensive liver necrosis and the presence of granulomas containing lymphocytes, Kupffer cells and polymorphonuclear leukocytes (PMN). In this condition, hepatic zymosan-induced light emission and MPO activity were enhanced over control values. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of lindane, which seems to be accomplished by potentiation of the hepatic oxidative stress status. The latter effect may be conditioned by an enhanced phagocytic respiratory burst activity due to the observed Kupffer cell hyperplasia and PMN infiltration, in addition to the increased production of reactive oxygen species in parenchymal cells.

Prooxidant and antioxidant hepatic factors in rats chronically fed an ethanol regimen and treated with an acute dose of lindane.

While acute lindane treatment and chronic ethanol feeding to rats have been associated with hepatic oxidative stress, the possible roles of these stresses in the pathogenesis of hepatic lesions reported in acute lindane intoxication and in those observed in some models of chronic alcoholism have not been established. Our previous studies in rats chronically fed ethanol regimens and then treated with a single intraperitoneal (i.p.) dose of lindane (20 mg/kg) showed that while lindane per se was invariably associated with hepatic oxidative stress, chronic ethanol feeding only produced this stress when the dietary level of vitamin E was relatively low. Chronic ethanol pretreatment did not significantly affect the lindane-associated oxidative stress, and neither chronic ethanol feeding nor acute lindane, single or in combination, produced any histologic and biochemical evidence of liver damage. In the present experiment, the acute dose of lindane was increased to 40 mg/kg, and we have studied a larger number of prooxidant and antioxidant hepatic factors. Male Wistar rats (115.5 +/- 5.4 g) were fed ad lib for 11 weeks a calorically well-balanced and nutritionally adequate basal diet, or the same basal diet plus a 32% ethanol/25% sucrose solution, also ad lib, and were then injected i.p. with a single dose of lindane or with equivalent amounts of corn oil. The results indicated that acute lindane treatment to naive rats increased practically all the prooxidant hepatic factors examined (cytochromes P450 and b5, NADPH cytochrome c reductase, NADPH oxidase), as well as the generation of microsomal superoxide radical and thiobarbituric acid reactive substances of liver homogenates, but did not modify any of the antioxidant hepatic factors studied. Conversely, the chronic administration of ethanol alone did not significantly affect the prooxidant hepatic factors but reduced some of the antioxidants (i.e., the activities of GSH-Px and the contents of alpha-tocopherol and ubiquinols 9 and 10). Although chronic ethanol pretreatment further increased the superoxide generation induced by lindane per se, it did not increase but generally reduced the effects of lindane per se on the other prooxidant factors studied. Furthermore, although acute lindane administration to ethanol-pretreated rats was associated with decreases in GSH and catalase (not affected by ethanol or lindane treatment alone), it did not substantially modify the reducing effects of ethanol feeding per se on GSH-Px, alpha-tocopherol, and ubiquinols. Once again, neither chronic ethanol feeding nor lindane treatment, single or in combination, was associated with any evidence of liver damage.