Estimating national-level measles case-fatality ratios in low-income and middle-income countries: an updated systematic review and modelling study

Background: To understand the current measles mortality burden, and to mitigate the future burden, it is crucial to have robust estimates of measles case fatalities. Estimates of measles case-fatality ratios (CFRs) that are specific to age, location, and time are essential to capture variations in underlying population-level factors, such as vaccination coverage and measles incidence, which contribute to increases or decreases in CFRs. In this study, we updated estimates of measles CFRs by expanding upon previous systematic reviews and implementing a meta-regression model. Our objective was to use all information available to estimate measles CFRs in low-income and middle-income countries (LMICs) by country, age, and year. Method(s): For this systematic review and meta-regression modelling study, we searched PubMed on Dec 31, 2020 for all available primary data published from Jan 1, 1980 to Dec 31, 2020, on measles cases and fatalities occurring up to Dec 31, 2019 in LMICs. We included studies that previous systematic reviews had included or which contained primary data on measles cases and deaths from hospital-based, community-based, or surveillance-based reports, including outbreak investigations. We excluded studies that were not in humans, or reported only data that were only non-primary, or on restricted populations (eg, people living with HIV), or on long-term measles mortality (eg, death from subacute sclerosing panencephalitis), and studies that did not include country-level data or relevant information on measles cases and deaths, or were for a high-income country. We extracted summary data on measles cases and measles deaths from studies that fitted our inclusion and exclusion criteria. Using these data and a suite of covariates related to measles CFRs, we implemented a Bayesian meta-regression model to produce estimates of measles CFRs from 1990 to 2019 by location and age group. This study was not registered with PROSPERO or otherwise. Finding(s): We identified 2705 records, of which 208 sources contained information on both measles cases and measles deaths in LMICS and were included in the review. Between 1990 and 2019, CFRs substantially decreased in both community-based and hospital-based settings, with consistent patterns across age groups. For people aged 0-34 years, we estimated a mean CFR for 2019 of 1.32% (95% uncertainty interval [UI] 1.28-1.36) among community-based settings and 5.35% (5.08-5.64) among hospital-based settings. We estimated the 2019 CFR in community-based settings to be 3.03% (UI 2.89-3.16) for those younger than 1 year, 1.63% (1.58-1.68) for age 1-4 years, 0.84% (0.80-0.87) for age 5-9 years, and 0.67% (0.64-0.70) for age 10-14 years. Interpretation(s): Although CFRs have declined between 1990 and 2019, there are still large heterogeneities across locations and ages. One limitation of this systematic review is that we were unable to assess measles CFR among particular populations, such as refugees and internally displaced people. Our updated methodological framework and estimates could be used to evaluate the effect of measles control and vaccination programmes on reducing the preventable measles mortality burden. Funding(s): Bill & Melinda Gates Foundation;Gavi, the Vaccine Alliance;and the US National Institutes of Health.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Technological Low Hanging Fruits Involved in Combating the COVID 19 Pandemic

This contribution describes some activities promoted by a group of roboticists from Istituto Italiano di Tecnologia and Università di Pisa in response to the pandemic. In particular, a “do-it-yourself” (DIY) open-source service and related hardware/products will be illustrated to help combat some consequences of the Covid 19 emergency. The project was born to facilitate communication between patients isolated in Covid 19 hospitals’ ward and their relatives. The teleoperated robot named LHF Connect can move autonomously around the hospital. Once it arrives at each patient's bed, it can provide a video call between patients and their relatives or friends outside the isolated hospital ward. In this scenario, the robot is piloted by a volunteer operator working from home or in a safe room inside the hospital. The teleoperator will guide LHF Connect toward each patient's bed using a laptop or a smartphone. LHF Connect is an open-source platform that leverages mature robotics technologies designed to be easily reproducible even in extreme conditions such as lockdown situations. The platform was reproduced during the first pandemic outbreak in Europe by other people independently, and it has been tested by medical staff in real scenarios and isolated Covid 19 departments. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Compassionate use of pulmonary vasodilators in acute severe hypoxic respiratory failure due to COVID-19

Introduction: There have been over 200 million cases and 4.4 million deaths from Covid-19 worldwide. In the UK over half a million have required hospitalisation, with over 130,000 deaths. Although most experience a mild illness the mortality can be over 50% for those requiring mechanical ventilation.1 One potential treatment for severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, either as nitric oxide (NO) or prostaglandin analogues. Despite the lack of robust evidence IPVDs are often considered recue treatments for refractory hypoxaemia.2,3 Given the disease severity in COVID-19 we implemented a protocol for the use of IPVDs on a compassionate basis for patients with severe hypoxaemia receiving otherwise maximal support. In this study we detail our findings and assess differences between survivors and non-survivors. Objectives: The primary outcome of this study was percentage changes in PaO2/FiO2 (PF) ratio and Alveolararterial (A-a) gradient at 2, 6, 12, 24, 48 and 72 hours following initiation of IPVD therapy. Secondary outcomes were differences in characteristics and response to therapy between survivors and non-survivors who received an IPVD. Methods: Data from a prospectively maintained research database of patients with SARS-CoV-2 admitted to the ICU at a large teaching hospital were analysed for the time period 14 March 2020 -11 February 2021. Patients aged 18 years or older who received an IPVD during their admission were eligible for inclusion. An IPVD was considered if the PF ratio was less than 13.3kPa despite rescue therapies (prone positioning, neuromuscular blockade, airway pressure release ventilation). Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced at 10-30mcg four hourly and NO weaned. Results: Three-hundred eight patients with SARS-Cov-2 were admitted during the study period of whom 59 (19.2%) received IPVD therapy. Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p=0.002) and higher APACHE-II score (17 vs. 13, p=0.028) at admission compared to those who did not. Survival to ICU discharge was lower in patients receiving an IPVD (55.9% vs. 81.9%, p<0.001). The median PF ratio at commencing IPVD therapy was 11.33kPa (9.93-12.91) with a median of 6 days from admission to receiving an IPVD. At 72 hours the median improvement in PF ratio was 33.9% (-4.3-84.1). In patients receiving IPVDs there were no differences in other therapies received (steroids, prone ventilation, ECMO) between survivors (n=33) and non-survivors (n=26), with the exception of renal replacement therapy. At 72 hours changes in PF ratio (70.8 vs. -4.1%) and reduction in A-a gradient (44.7 vs. 14.8%) differed significantly between survivors and non-survivors (both p <0.001). Conclusion: The response to the compassionate use of IPVDs for patients with acute hypoxic respiratory failure due to Covid-19 differs significantly between survivors and non-survivors. Both NO and inhaled prostaglandins may offer therapeutic options for severe hypoxaemia due to COVID-19, with prostaglandins particularly attractive as they do not require specialist delivery systems. The use of inhaled prostaglandins, and NO where feasible, should be studied in both isolation and combination in adequately powered prospective randomised trials.

Progress towards regional measles elimination - worldwide, 2000-2020

This report describes the progress towards WHA milestones and measles elimination objectives during 2000-2020 and updates a previous report. During 2000-2010, estimated MCV first dose (MCV1)coverage increased globally from 72% to 84%, peaked at 86% in 2019, and declined to 84% in 2020 during the COVID-19 pandemic. All countries conducted measlesurveillance, although fewer than one third achieved the sensitivity indicator target of 2 discarded cases per 100,000 population in 2020. From 2000 to 2016, annual reported measles incidence fell 88%, from 145 to 18 cases per 1 million population, before rebounding to 120 in 2019 and falling to 22 in 2020. During 2000-2020, the annual number of estimated measles deaths decreased by 94%, from 1,072,800 to 60,700, averting an estimated 31.7 million measles deaths. To reach regional measles eradication goals, more work needs to be done to make sure all children get two MCV doses, to have strong surveillance, and to find and close immunity gaps.

PRRT and SARS-COV-2 pandemic: could they live together? The experience of European Institute of Oncology (IEO), Milano Italy

Background-Aim: The importance of timely assistance in oncological patients is undeniable;however it is well known that these patients could have important clinical problems if they were infected by COVID-19, with an increased risk of severe illness and mortality. A recent multicenter Italian study reported a delay both in the beginning of PRRT for new patients (about 45.5% of centers) and in those ones who had already started the treatment (15%), as a direct consequence of COVID-19. The aim of this study was to understand if SARS-CoV2 infection has modified our clinical management, with particular attention to PRRT. Methods: In our ENETS Center of Excellence, the weekly multidisciplinary tumor board never stopped, also during the pandemic period. During these periods, the patients were treated with PRRT in the same way of previous years, remaining one night in Radiometabolic Therapy Unit, according to local laws. During COVID-19 pandemic, the patients received the PCR test the day before the treatment, while the day of PRRT they received a particular triage for avoid admitting patients with Sars-CoV-2 infection. We made a comparison between the number of PRRT cycles (either in clinical practice or in clinical trials) performed at European Institute of Oncology (IEO) from February 2020 to July 2021, with those performed in the previous year (February 2019-January 2020). Results: From February 2019 to January 2020, we performed 10 PRRT cycles, instead in the following months, during and despite of COVID-19 pandemic, from February 2020 to July 2021, we increased the number of patients treated. In fact 126 PRRT cycles were performed without any delay (either in clinical practice or in clinical trials). Only one Italian patient was unable to receive the treatment at IEO because he couldn't travel during lockdown period, so he performed PRRT near home. On the contrary, another patient coming from a different Nation, received PRRT on time. During this period, only two patients were affected by COVID-19 at the end of the treatment even if they were not yet vaccinated and, fortunately, the disease was mild, without consequences. These patients didn't stopped the therapy with SSA during COVID-19 disease. Moreover we performed a dosimetric study in almost all the patients during the first cycle of PRRT. Conclusions: These results focusing on PRRT treatments and COVID-19 pandemic, show that centers with more experience are able to adapt to the new global situation and to the new rules imposed by governments, providing continuity in care without any delay and even to increase the number of treatments.

Mortality incidence for SARS-COV-2 non-survivor infected in Colombia: A potential vaccination priority guide based on Comorbidities

The SARS-CoV-2 vaccination plan development in Colombia, set to begin in February 2021, included a comprehensive assessment of the spread to set population priorities in rank-ordered phases. In Phase 3 of the plan, populations between 16 and 59 years with a set of specific comorbidities will be vaccinated. Our study aims to evaluate the comorbidities incidence in the survival probability to assess the population at most risk if infected and assist in the assignation on this phase. In this study, multivariate Cox regression and Kaplan-Meier curves were performed to determine risk predictors of mortality for 610 reports of up to 15-day decay non-survivor SARS-CoV-2 infected in Colombia. After implementation, higher hazard ratios were associated with diabetes. Kaplan-Meier curves indicate that patients with diabetes that have an older age and hypertension are at a higher risk of earlier death. © IEOM Society International.

COVID-19 or not COVID-19, that is the question. The role of screening criteria and point-of-care lung ultrasound in the triage decision-making process in an Emergency Department during the phase 2 of the COVID-19 Italian epidemic

In the COVID-19 era the real challenge for the Emergency Departments (ED) is to avoid the spread of the viral infection within the so called "clean area" of the emergency room and the hospital. Different protocols have been proposed and adopted in the EDs to quickly identify suspected COVID-19 patients and to correctly manage these patients, all based on clinical and epidemiological criteria. To the best of our knowledge, our pre-triage decisional making-process first integrates the pre-triage interview with point-of-care Lung Ultrasound (LUS) performed in the triage area. The aim of our study is to assess the sensitivity and specificity of our screening clinical and/or epidemiological criteria, and to investigate the role of LUS in the triage decision-making process during the "phase 2" of the COVID-19 Italian epidemic. Our study confirms the pivotal role of the triage in the decision-making process and the management of the entire ED, and it demonstrates that further studies are necessary to validate the role of LUS as tool to promptly identify COVID-19 patients, if combined with a correct pre-triage interview.

LHF Connect: A DIY telepresence robot against COVID-19

This contribution describes a case study of a "do-it-yourself" (DIY) opensource service and related product to help combating the COVID-19 emergency. It illustrates the birth of LHF Connect, a project designed to facilitate communication between patients isolated in COVID-19 hospitals' ward and their relatives. LHF Connect is a teleoperated robot that can move in autonomy around the hospital. A User Centered Design approach, methods and specific tools helped in managing crucial steps of the design process such as i) the collection of needs coming from the context, stakeholders and end-users;ii) defining the service blueprint;iii) imagining finishing concepts;and iv) managing the communication activities. The initiative has been promoted by a multidisciplinary team of researchers (mainly roboticists with the help of specific competences coming from Design discipline). © 2020 Universidade do Vale do Rio dos Sinos. All rights reserved.

Clinical characteristics and outcome of critically ill COVID-19 patients with acute kidney injury: a single centre cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. METHODS: We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. RESULTS: A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. CONCLUSION: Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.

Vaccination strategies for measles control and elimination: time to strengthen local initiatives.

BACKGROUND: Through a combination of strong routine immunization (RI), strategic supplemental immunization activities (SIA) and robust surveillance, numerous countries have been able to approach or achieve measles elimination. The fragility of these achievements has been shown, however, by the resurgence of measles since 2016. We describe trends in routine measles vaccine coverage at national and district level, SIA performance and demographic changes in the three regions with the highest measles burden. FINDINGS: WHO-UNICEF estimates of immunization coverage show that global coverage of the first dose of measles vaccine has stabilized at 85% from 2015 to 19. In 2000, 17 countries in the WHO African and Eastern Mediterranean regions had measles vaccine coverage below 50%, and although all increased coverage by 2019, at a median of 60%, it remained far below levels needed for elimination. Geospatial estimates show many low coverage districts across Africa and much of the Eastern Mediterranean and southeast Asian regions. A large proportion of children unvaccinated for MCV live in conflict-affected areas with remote rural areas and some urban areas also at risk. Countries with low RI coverage use SIAs frequently, yet the ideal timing and target age range for SIAs vary within countries, and the impact of SIAs has often been mitigated by delays or disruptions. SIAs have not been sufficient to achieve or sustain measles elimination in the countries with weakest routine systems. Demographic changes also affect measles transmission, and their variation between and within countries should be incorporated into strategic planning. CONCLUSIONS: Rebuilding services after the COVID-19 pandemic provides a need and an opportunity to increase community engagement in planning and monitoring services. A broader suite of interventions is needed beyond SIAs. Improved methods for tracking coverage at the individual and community level are needed together with enhanced surveillance. Decision-making needs to be decentralized to develop locally-driven, sustainable strategies for measles control and elimination.