The physiologic benefits of optimizing cardiorespiratory fitness and physical activity - From the cell to systems level in a post-pandemic world.

Cardiovascular (CV) disease (CVD) is a leading cause of premature death and hospitalization which places a significant strain on health services and economies around the World. Evidence from decades of empirical and observational research demonstrates clear associations between physical activity (PA) and cardiorespiratory fitness (CRF) which can offset the risk of mortality and increase life expectancy and the quality of life in patients. Whilst well documented, the narrative of increased CRF remained pertinent during the coronavirus disease 2019 (COVID-19) pandemic, where individuals with lower levels of CRF had more than double the risk of dying from COVID-19 compared to those with a moderate or high CRF. The need to better understand the mechanisms associated with COVID-19 and those that continue to be affected with persistent symptoms following infection (Long COVID), and CV health is key if we are to be able to effectively target the use of CRF and PA to improve the lives of those suffering its afflictions. Whilst there is a long way to go to optimise PA and CRF for improved health at a population level, particularly in a post-pandemic world, increasing the understanding using a cellular-to-systems approach, we hope to provide further insight into the benefits of engaging in PA.

Using cardiorespiratory fitness assessment to identify pathophysiology in long COVID - Best practice approaches.

Cardio-respiratory fitness (CRF) is well-established in the clinical domains as an integrative measure of the body's physiological capability and capacity to transport and utilise oxygen during controlled bouts of physical exertion. Long COVID is associated with >200 different symptoms and is estimated to affect ∼150 million people worldwide. The most widely reported impact is reduced quality of life and functional status due to highly sensitive and cyclical symptoms that manifest and are augmented following exposure to physical, emotional, orthostatic, and cognitive stimuli, more commonly known as post-exertional symptom exacerbation (PESE) which prevents millions from engaging in routine daily activities. The use of cardiopulmonary exercise testing (CPET) is commonplace in the assessment of integrated physiology; CPET will undoubtedly play an integral role in furthering the pathophysiology and mechanistic knowledge that will inform bespoke Long COVID treatment and management strategies. An inherent risk of previous attempts to utilise CPET protocols in patients with chronic disease is that these are compounded by PESE and have induced a worsening of symptoms for patients that can last for days or weeks. To do this effectively and to meet the global need, the complex multi-system pathophysiology of Long COVID must be considered to ensure the design and implementation of research that is both safe for participants and capable of advancing mechanistic understanding.

Can Outreach Training and Supportive Supervision Improve Competency in Malaria Service Delivery? An Evaluation in Cameroon, Ghana, Niger, and Zambia.

Outreach Training and Supportive Supervision (OTSS) of malaria services at health facilities has been adopted by numerous malaria-endemic countries. The OTSS model is characterized by a hands-on method to enhance national guidelines and supervision tools, train supervisors, and perform supervision visits. An independent evaluation was conducted to evaluate the effectiveness of OTSS on health worker competence in the clinical management of malaria, parasitological diagnosis, and prevention of malaria in pregnancy. From 2018 to 2021, health facilities in Cameroon, Ghana, Niger, and Zambia received OTSS visits during which health workers were observed directly during patient consultations, and supervisors completed standardized checklists to assess their performance. Mixed-effects logistic regression models were developed to assess the impact of increasing OTSS visit number on a set of eight program-generated outcome indicators, including overall competency and requesting a confirmatory malaria test appropriately. Seven of eight outcome indicators showed evidence of beneficial effects of increased OTSS visits. Odds of health workers reaching competency thresholds for the malaria-in-pregnancy checklist increased by more than four times for each additional OTSS visit (odds ratio [OR], 4.62; 95% CI, 3.62-5.88). Each additional OTSS visit was associated with almost four times the odds of the health worker foregoing antimalarial prescriptions for patients who tested negative for malaria (OR, 3.80; 95% CI, 2.35-6.16). This evaluation provides evidence that successive OTSS visits result in meaningful improvements in indicators linked to quality case management of patients attending facilities for malaria diagnosis and treatment, as well as quality malaria prevention services received by women attending antenatal services.

Long COVID quality of life and healthcare experiences in the UK: a mixed method online survey.

PURPOSE: The complexity of long COVID and its diverse symptom profile contributes to unprecedented challenges for patients, clinicians, and healthcare services. The threat of long COVID remains ignored by Governments, the media and public health messaging, and patients' experiences must be heard through understanding of the lived experience. This study aimed to understand the lived experience of those living with long COVID. METHODS: An online web-based survey was designed using Patient and Public Involvement and Engagement (PPIE) to increase understanding of the lived experiences of long COVID, and was distributed through PPIE groups, social media, and word of mouth. The survey used closed and open questions relating to demographics, pre- and post-COVID-19 health quality of life, daily activities and long COVID experiences. RESULTS: Within our sample of 132 people living with long COVID, the findings highlight that individuals are being severely impacted by their symptoms and are unable to or limited in participating in their daily activities, reducing quality of life. Long COVID places strain on relationships, the ability to live life fully and is detrimental to mental health. Varying health care experiences are described by participants, with reports of medical gaslighting and inadequate support received. CONCLUSIONS: Long COVID has a severe impact on the ability to live life fully, and strains mental health. The appropriate mechanisms and support services are needed to support those living with long COVID and manage symptoms.

Acute COVID-19, the Lived Experience, and Lessons to Learn for Future Pandemics.

OBJECTIVES: The study aimed to increase the understanding of the lived experience of patients during the acute phase of a coronavirus disease 2019 (COVID-19) infection. METHOD: A Web-based survey was distributed through established patient and public engagement and involvement groups and networks, social media, and by means of word of mouth. The survey covered questions relating to patient demographics, COVID-19 diagnosis, symptom profile, and patient experience during acute COVID-19. RESULTS: The findings demonstrate the varying symptom profiles experienced by people in the acute stage of COVID-19 infection, with participants sharing how they managed care at home, and/or accessed medical advice. Findings also highlight themes that people were concerned with being unable to receive care and believed they needed to rely heavily on family, with extreme thoughts of death. CONCLUSIONS: Although the urgent threat to public health has been negated by efficacious vaccines and enhanced treatment strategies, there are key lessons from the lived experience of COVID-19 that should be used to prepare for future pandemics and public health emergencies.

Master statistical analysis plan: attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

This manuscript is a master statistical analysis plan for each of three-cluster randomized controlled trials to evaluate the efficacy of attractive targeted sugar baits (ATSB) described in an already published protocol. The master SAP contains an overarching plan for all three trials, which can be adapted to trial-specific circumstances. The primary objective of the trials is to evaluate the efficacy of ATSB in the presence of universal vector control coverage with insecticide-treated nets (ITN) or indoor residual spraying (IRS) after two transmission seasons on clinical malaria incidence as compared with universal vector control coverage with ITN or IRS alone. The primary outcome measure is the incidence rate of clinical malaria, assessed in cohorts aged 12 months to less than 15 years (≥ 5 years to 15 years in Mali) during monthly follow-up visits. The primary unadjusted analysis will be conducted on the intention-to-treat analysis population without adjustment for any anticipated confounding variables. The primary outcome will be analyzed using a multi-level model constructed on a generalized linear model framework with a Poisson likelihood and a log link function. Random intercepts will be included for each study cluster and a fixed effect for study-arm. The analyst will be blinded to study arm assignment. Several secondary outcomes will be analyzed, as well as a pooled analysis (individual patient data meta-analysis) across the three trial sites. Additionally, a standard meta-analysis is expected to be conducted using combined data from all sites.

Forming a consensus opinion to inform long COVID support mechanisms and interventions: a modified Delphi approach.

Background: Current approaches to support patients living with post-COVID condition, also known as Long COVID, are highly disparate with limited success in managing or resolving a well-documented and long-standing symptom burden. With approximately 2.1 million people living with the condition in the UK alone and millions more worldwide, there is a desperate need to devise support strategies and interventions for patients. Methods: A three-round Delphi consensus methodology was distributed internationally using an online survey and was completed by healthcare professionals (including clinicians, physiotherapists, and general practitioners), people with long COVID, and long COVID academic researchers (round 1 n = 273, round 2 n = 186, round 3 n = 138). Across the three rounds, respondents were located predominantly in the United Kingdom (UK), with 17.3-15.2% (round 1, n = 47; round 2 n = 32, round 2 n = 21) of respondents located elsewhere (United States of America (USA), Austria, Malta, United Arab Emirates (UAE), Finland, Norway, Malta, Netherlands, Iceland, Canada, Tunisie, Brazil, Hungary, Greece, France, Austrailia, South Africa, Serbia, and India). Respondents were given ∼5 weeks to complete the survey following enrolment, with round one taking place from 02/15/2022 to 03/28/22, round two; 05/09/2022 to 06/26/2022, and round 3; 07/14/2022 to 08/09/2022. A 5-point Likert scale of agreement was used and the opportunity to include free text responses was provided in the first round. Findings: Fifty-five statements reached consensus (defined as >80% agree and strongly agree), across the domains of i) long COVID as a condition, ii) current support and care available for long COVID, iii) clinical assessments for long COVID, and iv) support mechanisms and rehabilitation interventions for long COVID, further sub-categorised by consideration, inclusion, and focus. Consensus reached proposes that long COVID requires specialised, comprehensive support mechanisms and that interventions should form a personalised care plan guided by the needs of the patients. Supportive approaches should focus on individual symptoms, including but not limited to fatigue, cognitive dysfunction, and dyspnoea, utilising pacing, fatigue management, and support returning to daily activities. The mental impact of living with long COVID, tolerance to physical activity, emotional distress and well-being, and research of pre-existing conditions with similar symptoms, such as myalgic encephalomyelitis, should also be considered when supporting people with long COVID. Interpretation: We provide an outline that achieved consensus with stakeholders that could be used to inform the design and implementation of bespoke long COVID support mechanisms. Funding: None.

Acceptability, Feasibility, Drug Safety, and Effectiveness of a Pilot Mass Drug Administration with a Single Round of Sulfadoxine-Pyrimethamine Plus Primaquine and Indoor Residual Spraying in Communities with Malaria Transmission in Haiti, 2018.

For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.

Lived experience of patients with Long COVID: a qualitative study in the UK.

BACKGROUND: Long COVID is a rapidly evolving global health crisis requiring interdisciplinary support strategies that incorporate the lived experience of patients. Currently, there is a paucity of research documenting the day-to-day experiences of patients living with Long COVID. OBJECTIVE: To explore the lived experience of Long COVID patients. STUDY DESIGN: Longitudinal, observation study. SETTING: An inductive, data-driven, qualitative approach was used to evaluate hand-written diaries obtained from individuals who had been referred to a Derbyshire Long COVID clinic. PARTICIPANTS: 12 participants (11 females, age 49±10 years, 11 Caucasians) were recruited. Participants were included if they had a previous confirmed or suspected COVID-19 infection with ongoing recovery, >18 years old, understood the study requirements and provided informed consent. METHOD: Participants were directed to complete self-report diaries over 16 weeks. Responses were transcribed verbatim and analysed using thematic analysis. RESULTS: Three key themes were highlighted: (1) understanding who helps patients manage symptoms, (2) daily activities and the impact on quality of life and health status and (3) the effect of turbulent and episodic symptom profiles on personal identity and recovery. CONCLUSIONS: The novel challenges presented by Long COVID are complex with varying inter-related factors that are broadly impacting functional status and quality of life. Support mechanisms must incorporate the lived experiences and foster true collaborations between health professionals, patients and researchers to improve patient outcomes. TRIAL REGISTRATION NUMBER: NCT04649957.

A united approach to promoting healthy living behaviours and associated health outcomes: a global call for policymakers and decisionmakers.

Chronic disease pandemics have challenged societies and public health throughout history and remain ever-present. Despite increased knowledge, awareness and advancements in medicine, technology, and global initiatives the state of global health is declining. The coronavirus disease 2019 (COVID-19) pandemic has compounded the current perilous state of global health, and the long-term impact is yet to be realised. A coordinated global infrastructure could add substantial benefits to public health and yield prominent and consistent policy resulting in impactful change. To achieve global impact, research priorities that address multi-disciplinary social, environmental, and clinical must be supported by unified approaches that maximise public health. We present a call to action for established public health organisations and governments globally to consider the lessons from the COVID-19 pandemic and unite with true collaborative efforts to address current, longstanding, and growing challenges to public health.

Feeding rates of malaria vectors from a prototype attractive sugar bait station in Western Province, Zambia: results of an entomological validation study.

BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a promising new approach to malaria vector control that could compliment current tools by exploiting the natural sugar feeding behaviors of mosquitoes. Recent proof of concept work with a prototype ATSB® Sarabi Bait Station (Westham Co., Hod-Hasharon, Israel) has demonstrated high feeding rates and significant reductions in vector density, human biting rate, and overall entomological inoculation rate for Anopheles gambiae sensu lato (s.l.) in the tropical savannah of western Mali. The study reported here was conducted in the more temperate, rainier region of Western Province, Zambia and was designed to confirm the primary vector species in region and to estimate corresponding rates of feeding from prototype attractive sugar bait (ASB) Sarabi Bait Stations. METHODS: The product evaluated was the Sarabi v1.1.1 ASB station, which did not include insecticide but did include 0.8% uranine as a dye allowing for the detection, using UV fluorescence light microscopy, of mosquitoes that have acquired a sugar meal from the ASB. A two-phase, crossover study design was conducted in 10 village-based clusters in Western Province, Zambia. One study arm initially received 2 ASB stations per eligible structure while the other initially received 3. Primary mosquito sampling occurred via indoor and outdoor CDC Miniature UV Light Trap collection from March 01 through April 09, 2021 (Phase 1) and from April 19 to May 28, 2021 (Phase 2). RESULTS: The dominant vector in the study area is Anopheles funestus s.l., which was the most abundant species group collected (31% of all Anophelines; 45,038/144,5550), had the highest sporozoite rate (3.16%; 66 positives out of 2,090 tested), and accounted for 94.3% (66/70) of all sporozoite positive specimens. Of those An. funestus specimens further identified to species, 97.2% (2,090/2,150) were An. funestus sensu stricto (s.s.). Anopheles gambiae s.l. (96.8% of which were Anopheles arabiensis) is a likely secondary vector and Anopheles squamosus may play a minor role in transmission. Overall, 21.6% (9,218/42,587) of An. funestus specimens and 10.4% (201/1,940) of An. gambiae specimens collected were positive for uranine, translating into an estimated daily feeding rate of 8.9% [7.7-9.9%] for An. funestus (inter-cluster range of 5.5% to 12.7%) and 3.9% [3.3-4.7%] for An. gambiae (inter-cluster range of 1.0-5.2%). Feeding rates were no different among mosquitoes collected indoors or outdoors, or among mosquitoes from clusters with 2 or 3 ASBs per eligible structure. Similarly, there were no correlations observed between feeding rates and the average number of ASB stations per hectare or with weekly rainfall amounts. CONCLUSIONS: Anopheles funestus and An. gambiae vector populations in Western Province, Zambia readily fed from the prototype Sarabi v1.1.1 ASB sugar bait station. Observed feeding rates are in line with those thought to be required for ATSB stations to achieve reductions in malaria transmission when used in combination with conventional control methods (IRS or LLIN). These results supported the decision to implement a large-scale, epidemiological cluster randomized controlled trial of ATSB in Zambia, deploying 2 ATSB stations per eligible structure.

The Impact of COVID-19 on the Social Determinants of Cardiovascular Health.

Cardiovascular disease is the leading noncommunicable disease and cause of premature mortality globally. Despite well established evidence of a cause-effect relationship between modifiable lifestyle behaviours and the onset of risk of chronic disease, preventive approaches to curtail increasing prevalence have been ineffective. This has undoubtedly been exacerbated by the response to COVID-19, which saw widespread national lockdowns implemented to reduce transmission and alleviate pressure on strained health care systems. A consequence of these approaches was a well documented negative impact on population health in the context of both physical and mental well-being. Although the true extent of the impact of the COVID-19 response on global health has yet to be fully realised or understood, it seems prudent to review effective preventative and management strategies that have yielded positive outcomes across the spectrum (ie, from individual to society). There is also a clear need to heed lessons learned from the COVID-19 experience in the power of collaboration and how this can be used in the design, development, and implementation of future approaches to address the longstanding burden of cardiovascular disease.

Effectiveness of community case management of malaria on severe malaria and inpatient malaria deaths in Zambia: a dose-response study using routine health information system data.

BACKGROUND: Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria. METHODS: This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose-response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia's interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding. RESULTS: The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75-0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66-0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population. CONCLUSIONS: CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.

The acute and chronic implications of the COVID-19 virus on the cardiovascular system in adults: A systematic review.

Despite coronavirus disease 2019 (COVID-19) primarily being identified as a respiratory illness, some patients who seemingly recovered from initial infection, developed chronic multi-system complications such as cardiovascular (CV), pulmonary and neurological issues leading to multiple organ injuries. However, to date, there is a dearth of understanding of the acute and chronic implications of a COVID-19 infection on the CV system in adults. A systematic review of the literature was conducted according to PRISMA guidelines and prospectively registered via Prospero (ID: CRD42022360444). The MEDLINE Ovid, Cochrane Library and PubMed databases were searched from inception to August 2022. The search strategy keywords and MeSH terms used included: 1) COVID; 2) coronavirus; 3) long COVID; 4) cardiovascular; and 5) cardiovascular disease. Reference lists of all relevant systematic reviews identified were searched for additional studies. A total of 11,332 records were retrieved from database searches, of which 310 records were duplicates. A further 9887 were eliminated following screening of titles and abstracts. After full-text screening of 1135 articles, 9 manuscripts were included for review. The evidence of CV implications post-COVID-19 infection is clear, and this must be addressed with appropriate management strategies that recognise the acute and chronic nature of cardiac injury in COVID-19 patients. Efficacious management strategies will be needed to address long standing issues and morbidity.

Cardiovascular disease prevention and management in the COVID-19 era and beyond: An international perspective.

Despite some indicators of a localized curtailing of cardiovascular disease (CVD) prevalence, CVD remains one of the largest contributors to global morbidity and mortality. While the magnitude and impact of the coronavirus disease 2019 (COVID-19) pandemic have yet to be realized in its entirety, an unquestionable impact on global health and well-being is already clear. At a time when the global state of CVD is perilous, we provide a continental overview of prevalence data and initiatives that have positively influenced CVD outcomes. What is clear is that despite attempts to address the global burden of CVD, there remains a lack of collective thinking and approaches. Moving forward, a coordinated global infrastructure that, if developed with appropriate and relevant key stakeholders, could provide significant and longstanding benefits to public health and yield prominent and consistent policy resulting in impactful change. To achieve global impact, research priorities that address multi-disciplinary social, environmental, and clinical perspectives must be underpinned by unified approaches that maximize public health.

Cardiorespiratory fitness as a vital sign of CVD risk in the COVID-19 era.

The severe health consequences of the corona virus disease 2019 (COVID-19) pandemic have been exacerbated by the prevalence of cardiovascular disease (CVD) risk factors, such as physical inactivity, obesity, hypertension, and diabetes. Further, policy decisions during the pandemic augmented unhealthy lifestyle behaviors and health inequalities, likely increasing the global disease burden. Cardiorespiratory fitness (CRF) is a well-established biomarker associated with CVD risk. Emerging data demonstrate that high CRF offers some protection against severe outcomes from COVID-19 infection, highlighting the importance of CRF for population health and the potential for limiting the severity of future pandemics. CRF is best assessed by cardiopulmonary exercise testing (CPET), which will be an important tool for understanding the prolonged pathophysiology of COVID-19, the emergence of long-COVID, and the lasting effects of COVID-19 on CVD risk. Utilization of CRF and CPET within clinical settings should become commonplace because of lessons learned from the COVID-19 pandemic.

COVID-19 and elite sport: Cardiovascular implications and return-to-play.

Curtailing elite sports during the coronavirus disease 2019 (COVID-19) pandemic was necessary to prevent widespread viral transmission. Now that elite sport and international competitions have been largely restored, there is still a need to devise appropriate screening and management pathways for athletes with a history of, or current, COVID-19 infection. These approaches should support the decision-making process of coaches, sports medicine practitioners and the athlete about the suitability to return to training and competition activities. In the absence of longitudinal data sets from athlete populations, the incidence of developing prolonged and debilitating symptoms (i.e., Long COVID) that affects a return to training and competition remains a challenge to sports and exercise scientists, sports medicine practitioners and clinical groups. As the world attempts to adjust toward 'living with COVID-19' the very nature of elite and international sporting competition poses a risk to athlete welfare that must be screened for and managed with bespoke protocols that consider the cardiovascular implications for performance.

Factors Associated With Human IgG Antibody Response to Anopheles albimanus Salivary Gland Extract, Artibonite Department, Haiti, 2017.

Serological data can provide estimates of human exposure to both malaria vector and parasite based on antibody responses. A multiplex bead-based assay was developed to simultaneously detect IgG to Anopheles albimanus salivary gland extract (SGE) and 23 Plasmodium falciparum antigens among 4185 participants enrolled in Artibonite department, Haiti in 2017. Logistic regression adjusted for participant- and site-level covariates and found children under 5 years and 6-15 years old had 3.7- and 5.4-fold increase in odds, respectively, of high anti-SGE IgG compared to participants >15 years. Seropositivity to P. falciparum CSP, Rh2_2030, and SEA-1 antigens was significantly associated with high IgG response against SGE, and participant enrolment at elevations under 200 m was associated with higher anti-SGE IgG levels. The ability to approximate population exposure to malaria vectors through SGE serology data is very dependent by age categories, and SGE antigens can be easily integrated into a multiplex serological assay.