Exceptional Prices of Medical and Other Supplies during the COVID-19 Pandemic in Ecuador.

Shortages of essential supplies used to prevent, diagnose, and treat COVID-19 have been a global concern, and price speculation and hikes may have negatively influenced access. This study identifies variability in prices of products acquired through government-driven contracts in Ecuador during the early pandemic response, when the highest mortality rates were registered in a single day. Data were obtained from the National Public Procurement Service (SERCOP) database between March 1 and July 31, 2020. A statistical descriptive analysis was conducted to extract relevant measures for commonly purchased products, medical devices, pharmaceutical drugs, and other goods. Among the most frequently purchased products, the greatest amounts were spent on face masks (US$4.5 million), acetaminophen (US$2.2 million), and reverse transcriptase quantitative polymerase chain reaction assay kits (US$1.8 million). Prices varied greatly, depending on each individual contract and on the number of units purchased; some were exceptionally higher than their market value. Compared with 2019, the mean price of medical examination gloves increased up to 1,307%, acetaminophen 500 mg pills, up to 796%, and oxygen flasks, 30.8%. In a context of budgetary constraints that actually required an effective use of available funds, speculative price hikes may have limited patient access to health care and the protection of the general population and health care workers. COVID-19 vaccine allocations to privileged individuals have also been widely reported. Price caps and other forms of regulation, as well as greater scrutiny and transparency of government-driven purchases, and investment in local production, are warranted in Ecuador for improved infectious disease prevention

CPEB4 Increases Expression of PFKFB3 to Induce Glycolysis and Activate Mouse and Human Hepatic Stellate Cells, Promoting Liver Fibrosis

BACKGROUND & AIMS: We investigated mechanisms of hepatic stellate cell (HSC) activation, which contributes to liver fibrogenesis. We aimed to determine whether activated HSCs increase glycolysis, which is regulated by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and whether this pathway might serve as a therapeutic target. METHODS: We performed studies with primary mouse HSCs, human LX2 HSCs, human cirrhotic liver tissues, rats and mice with liver fibrosis (due to bile duct ligation [BDL] or administration of carbon tetrachlo- ride), and CPEB4-knockout mice. Glycolysis was inhibited in cells and mice by administration of a small molecule antagonist of PFKFB3 (3-[3-pyridinyl]-1-[4-pyridinyl]-2- propen-1-one [3PO]). Cells were transfected with small interfering RNAs that knock down PFKFB3 or CPEB4. RESULTS: Up-regulation of PFKFB3 protein and increased glycolysis were early and sustained events during HSC activation and accompanied by increased expression of markers of fibrogenesis; incubation of HSCs with 3PO or knockdown of PFKFB3 reduced their activation and prolif- eration. Mice with liver fibrosis after BDL had increased hepatic PFKFB3; injection of 3PO immediately after the surgery prevented HSC activation and reduced the severity of liver fibrosis compared with mice given vehicle. Levels of PFKFB3 protein were increased in fibrotic liver tissues from patients compared with non-fibrotic liver. Up-regulation of PFKFB3 in activated HSCs did not occur via increased transcription, but instead via binding of CPEB4 to cyto- plasmic polyadenylation elements within the 3'-untranslated regions of PFKFB3 messenger RNA. Knockdown of CPEB4 in LX2 HSCs prevented PFKFB3 overexpression and cell acti- vation. Livers from CPEB4-knockout had decreased PFKFB3 and fibrosis after BDL or administration of carbon tetra- chloride compared with wild-type mice. CONCLUSIONS: Fibrotic liver tissues from patients and rodents (mice and rats) have increased levels of PFKFB3 and glycolysis, which are essential for activation of HSCs. Increased expression of PFKFB3 is mediated by binding of CPEB4 to its untranslated messenger RNA. Inhibition or knockdown of CPEB4 or PFKFB3 prevents HSC activation and fibrogenesis in livers of mice

A proposed analytical approach to estimate excess daily mortality rates in Ecuador

BackgroundThe COVID-19 pandemic has proved deadly all over the globe; however, one of the most lethal outbreaks occurred in Ecuador.AimsThis study aims to highlight the pandemic’s impact on the most affected countries worldwide in terms of excess deaths per capita and per day.MethodsAn ecological study of all-cause mortality recorded in Ecuador was performed. To calculate the excess deaths relative to the historical average for the same dates in 2017, 2018, and 2019, we developed a bootstrap method based on the central tendency measure of mean. A Poisson fitting analysis was used to identify trends on officially recorded all-cause deaths and COVID-19 deaths. A bootstrapping technique was used to emulate the sampling distribution of our expected deaths estimator μ⌢deaths by simulating the data generation and model fitting processes daily since the first confirmed case.ResultsIn Ecuador, during 2020, 115,070 deaths were reported and 42,453 were cataloged as excess mortality when compared to 2017–2019 period. Ecuador is the country with the highest recorded excess mortality in the world within the shortest timespan. In one single day, Ecuador recorded 1,120 deaths (6/100,000), which represents an additional 408% of the expected fatalities.ConclusionAdjusting for population size and time, the hardest-hit country due to the COVID-19 pandemic was Ecuador. The mortality excess rate shows that the SARS-CoV-2 virus spread rapidly in Ecuador, especially in the coastal region. Our results and the proposed new methodology could help to address the real situation of the number of deaths during the initial phase of pandemics

Long COVID at different altitudes: A Countrywide Epidemiological Analysis

Background: Several reports from around the world have reported that some patients who have recovered from COVID-19 have experienced a range of persistent or new clinical symptoms after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (2500 m). Results: Overall, 1100 (52.3%) responders claimed to have Long-COVID symptoms after SARS-CoV-2 infection. Most of these were reported by women (64.0%); the most affected group was young adults between 21 to 40 years (68.5%), and most long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of symptoms was observed in the group that received less than 2 doses. Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 21-40, are more likely to describe Long-COVID. We also found that living at a high altitude was associated with higher reports of mood changes, tachycardia, decreased libido, insomnia, and palpitations compared to lowlanders. Finally, we found a greater risk to report Long-COVID symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection

SARS-CoV-2 viral load analysis at low and high altitude: A case study from Ecuador

SARS-CoV-2 has spread throughout the world, including remote areas such as those located at high altitudes. There is a debate about the role of hypobaric hypoxia on viral transmission and COVID-19 incidence. A descriptive cross-sectional analysis of SARS-CoV-2 infection and viral load among patients living at low (230 m) and high altitude (3800 m) in Ecuador was completed. Within these two communities, the total number of infected people at the time of the study was 108 cases (40.3%). The COVID-19 incidence proportion at low altitude was 64% while at high altitude was 30.3%. The mean viral load from those patients who tested positive was 3,499,184 copies/mL (SD = 23,931,479 copies/mL). At low altitude (Limoncocha), the average viral load was 140,223.8 copies/mL (SD = 990,840.9 copies/mL), while for the high altitude group (Oyacachi), the mean viral load was 6,394,789 copies/mL (SD = 32,493,469 copies/mL). We found no statistically significant differences when both results were compared (p = 0.056). We found no significant differences across people living at low or high altitude; however, men and younger populations had higher viral load than women older populations, respectivel

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A Systematic Review and Quality Evaluation of Studies on Long-Term Sequelae of COVID-19

COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being clarified. The aim of this study was to present an overview of the information available on the sequelae of COVID-19 in people who have suffered from the infection. A systematic review was carried out in which cohort studies, case series, and clinical case reports were included, and the PubMed, Scielo, SCOPUS, and Web of Science databases were extracted. Information was published from 2020 to 1 June 2022, and we included 26 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 8 for neurological and psychiatric, and 6 for cutaneous sequelae. Studies showed that the most common sequelae were those linked to the lungs, followed by skin, cutaneous, and psychiatric alterations. Women reported a higher incidence of the sequelae, as well as those with comorbidities and more severe COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its appearance, but it has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems, and further burden healthcare systems around the world

Analysis of Excess Mortality Data at Different Altitudes During the COVID-19 Outbreak in Ecuador

Ortiz-Prado, Esteban, Raul Patricio Fernandez Naranjo, Eduardo Vasconez, Katherine Simbaña-Rivera, Trigomar Correa-Sancho, Alex Lister, Manuel Calvopiña, and Ginés Viscor. Analysis of excess mortality data at different altitudes during the COVID-19 outbreak in Ecuador. High Alt Med Biol. 22:406-416, 2021. Background: It has been speculated that living at high altitude confers some risk reduction in terms of SARS-CoV-2 infection, reduced transmissibility, and arguable lower COVID-19-related mortality. Objective: We aim to determine the number of excess deaths reported in Ecuador during the first year of the COVID-19 pandemic in relation to different altitude categories among 221 cantons in Ecuador, ranging from sea level to 4,300 m above. Methods: A descriptive ecological country-wide analysis of the excess mortality in Ecuador was performed since March 1, 2020, to March 1, 2021. Every canton was categorized as lower (for altitudes 2,500 m or less) or higher (for altitudes &gt;2,500 m) in a first broad classification, as well as in two different classifications: The one proposed by Imray et al. in 2011 (low altitude &lt;1,500 m, moderate altitude 1,500-2,500 m, high altitude 2,500-3,500 m, or very high altitude 3,500-5,500 m) and the one proposed by Bärtsch et al. in 2008 (near sea level 0-500 m, low altitude 500-2,000 m, moderate altitude 2,000-3,000 m, high altitude 3,000-5,500 m, and extreme altitude 5,500 m). A Poisson fitting analysis was used to identify trends on officially recorded all-caused deaths and those attributed to COVID-19. Results: In Ecuador, at least 120,573 deaths were recorded during the first year of the pandemic, from which 42,453 were catalogued as excessive when compared with the past 3 years of averages (2017-2019). The mortality rate at the lower altitude was 301/100,000 people, in comparison to 242/100,000 inhabitants in elevated cantons. Considering the four elevation categories, the highest excess deaths came from towns located at low altitude (324/100,000), in contrast to the moderate altitude (171/100,000), high-altitude (249/100,000), and very high-altitude (153/100,000) groups. Conclusions: This is the first report on COVID-19 excess mortality in a high-altitude range from 0 to 4,300 m above sea level. We found that absolute COVID-19-related excess mortality is lower both in time and in proportion in the cantons located at high and very high altitude when compared with those cantons located at low altitude.</p