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The Global Biodiversity Framework (GBF), signed in 2022 by Parties to the Convention on Biological Diversity, recognized the importance of area-based conservation, and its goals and targets specify the characteristics of protected and conserved areas (PCAs) that disproportionately contribute to biodiversity conservation. To achieve the GBF's target of conserving a global area of 30% by 2030, this Essay argues for recognizing these characteristics and scaling them up through the conservation of areas that are: extensive (typically larger than 5,000 km2); have interconnected PCAs (either physically or as part of a jurisdictional network, and frequently embedded in larger conservation landscapes); have high ecological integrity; and are effectively managed and equitably governed. These areas are presented as "Nature's Strongholds," illustrated by examples from the Congo and Amazon basins. Conserving Nature's Strongholds offers an approach to scale up initiatives to address global threats to biodiversity.
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Biodiversidade , Conservação dos Recursos Naturais , Conservação dos Recursos Naturais/métodos , Ecossistema , Animais , CongoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Humanity will soon define a new era for nature-one that seeks to transform decades of underwhelming responses to the global biodiversity crisis. Area-based conservation efforts, which include both protected areas and other effective area-based conservation measures, are likely to extend and diversify. However, persistent shortfalls in ecological representation and management effectiveness diminish the potential role of area-based conservation in stemming biodiversity loss. Here we show how the expansion of protected areas by national governments since 2010 has had limited success in increasing the coverage across different elements of biodiversity (ecoregions, 12,056 threatened species, 'Key Biodiversity Areas' and wilderness areas) and ecosystem services (productive fisheries, and carbon services on land and sea). To be more successful after 2020, area-based conservation must contribute more effectively to meeting global biodiversity goals-ranging from preventing extinctions to retaining the most-intact ecosystems-and must better collaborate with the many Indigenous peoples, community groups and private initiatives that are central to the successful conservation of biodiversity. The long-term success of area-based conservation requires parties to the Convention on Biological Diversity to secure adequate financing, plan for climate change and make biodiversity conservation a far stronger part of land, water and sea management policies.
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Conservação dos Recursos Naturais/tendências , Mapeamento Geográfico , Animais , Organismos Aquáticos , Biodiversidade , Conservação dos Recursos Naturais/economia , Conservação dos Recursos Naturais/estatística & dados numéricos , Ecologia/estatística & dados numéricos , Ecologia/tendências , História do Século XXI , Meio SelvagemRESUMO
Reducing the rate of global biodiversity loss is a major challenge facing humanity1, as the consequences of biological annihilation would be irreversible for humankind2-4. Although the ongoing degradation of ecosystems5,6 and the extinction of species that comprise them7,8 are now well-documented, little is known about the role that remaining wilderness areas have in mitigating the global biodiversity crisis. Here we model the persistence probability of biodiversity, combining habitat condition with spatial variation in species composition, to show that retaining these remaining wilderness areas is essential for the international conservation agenda. Wilderness areas act as a buffer against species loss, as the extinction risk for species within wilderness communities is-on average-less than half that of species in non-wilderness communities. Although all wilderness areas have an intrinsic conservation value9,10, we identify the areas on every continent that make the highest relative contribution to the persistence of biodiversity. Alarmingly, these areas-in which habitat loss would have a more-marked effect on biodiversity-are poorly protected. Given globally high rates of wilderness loss10, these areas urgently require targeted protection to ensure the long-term persistence of biodiversity, alongside efforts to protect and restore more-degraded environments.
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Biodiversidade , Extinção Biológica , Modelos Biológicos , Meio Selvagem , Animais , Conservação dos Recursos Naturais , Comportamento de Redução do RiscoRESUMO
Eukaryotes have a multitude of diverse mechanisms for organising and using their genomes, but the histones that make up chromatin are highly conserved. Unusually, histones from kinetoplastids are highly divergent. The structural and functional consequences of this variation are unknown. Here, we have biochemically and structurally characterised nucleosome core particles (NCPs) from the kinetoplastid parasite Trypanosoma brucei. A structure of the T. brucei NCP reveals that global histone architecture is conserved, but specific sequence alterations lead to distinct DNA and protein interaction interfaces. The T. brucei NCP is unstable and has weakened overall DNA binding. However, dramatic changes at the H2A-H2B interface introduce local reinforcement of DNA contacts. The T. brucei acidic patch has altered topology and is refractory to known binders, indicating that the nature of chromatin interactions in T. brucei may be unique. Overall, our results provide a detailed molecular basis for understanding evolutionary divergence in chromatin structure.
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Histonas , Nucleossomos , Trypanosoma brucei brucei , Cromatina/genética , Cromatina/metabolismo , DNA/metabolismo , Histonas/metabolismo , Nucleossomos/genética , Nucleossomos/metabolismo , Trypanosoma brucei brucei/metabolismoRESUMO
We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.
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Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Masculino , Humanos , Vietnã/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Ásia , Análise EspacialRESUMO
Plasmodium vivax is now the main cause of malaria outside Africa. The gametocytocidal effects of antimalarial drugs are important to reduce malaria transmissibility, particularly in low-transmission settings, but they are not well characterized for P. vivax. The transmission-blocking effects of chloroquine, artesunate, and methylene blue on P. vivax gametocytes were assessed. Blood specimens were collected from patients presenting with vivax malaria, incubated with or without the tested drugs, and then fed to mosquitos from a laboratory-adapted colony of Anopheles dirus (a major malaria vector in Southeast Asia). The effects on oocyst and sporozoite development were analyzed under a multi-level Bayesian model accounting for assay variability and the heterogeneity of mosquito Plasmodium infection. Artesunate and methylene blue, but not chloroquine, exhibited potent transmission-blocking effects. Gametocyte exposures to artesunate and methylene blue reduced the mean oocyst count 469-fold (95% CI: 345 to 650) and 1,438-fold (95% CI: 970 to 2,064), respectively. The corresponding estimates for the sporozoite stage were a 148-fold reduction (95% CI: 61 to 470) and a 536-fold reduction (95% CI: 246 to 1,311) in the mean counts, respectively. In contrast, high chloroquine exposures reduced the mean oocyst count only 1.40-fold (95% CI: 1.20 to 1.64) and the mean sporozoite count 1.34-fold (95% CI: 1.12 to 1.66). This suggests that patients with vivax malaria often remain infectious to anopheline mosquitos after treatment with chloroquine. Use of artemisinin combination therapies or immediate initiation of primaquine radical cure should reduce the transmissibility of P. vivax infections.
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An emerging consensus suggests that evolved intraspecific variation can be ecologically important. However, evidence that evolved trait variation within vertebrates can influence fundamental ecosystem-level processes remains sparse. In this study, we sought to assess the potential for evolved variation in the spotted salamander (Ambystoma maculatum) to affect aquatic ecosystem properties. Spotted salamanders exhibit a conspicuous polymorphism in the colour of jelly encasing their eggs-some females produce clear jelly, while others produce white jelly. Although the functional significance of jelly colour variation remains largely speculative, evidence for differences in fecundity and the morphology of larvae suggests that the colour morphs might differ in the strength or identity of ecological effects. Here, we assessed the potential for frequency variation in spotted salamander colour morphs to influence fundamental physiochemical and ecosystem properties-dissolved organic carbon, conductivity, acidity and primary production-with a mesocosm experiment. By manipulating colour morph frequency across a range of larval densities, we were able to demonstrate that larva density and colour morph variation were ecologically relevant: population density reduced dissolved organic carbon and increased primary production while mesocosms stocked with white morph larvae tended to have higher dissolved organic carbon and conductivity. Thus, while an adaptive significance of jelly coloration remains hypothetical, our results show that colour morphs differentially influence key ecosystem properties-dissolved organic carbon and conductivity.
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Matéria Orgânica Dissolvida , Ecossistema , Animais , Feminino , Cor , Ambystoma , LarvaRESUMO
BACKGROUND: Effective antiviral drugs accelerate viral clearance in acute COVID-19 infections; the relationship between accelerating viral clearance and reducing severe clinical outcomes is unclear. METHODS: A systematic review was conducted of randomized controlled trials (RCTs) of antiviral therapies in early symptomatic COVID-19, where viral clearance data were available. Treatment benefit was defined clinically as the relative risk of hospitalization/death during follow-up (≥14â days), and virologically as the SARS-CoV-2 viral clearance rate ratio (VCRR). The VCRR is the ratio of viral clearance rates between the intervention and control arms. The relationship between the clinical and virological treatment effects was assessed by mixed-effects meta-regression. RESULTS: From 57 potentially eligible RCTs, VCRRs were derived for 44 (52â384 participants); 32 had ≥1 clinical endpoint in each arm. Overall, 9.7% (R2) of the variation in clinical benefit was explained by variation in VCRRs with an estimated linear coefficient of -0.92 (95% CI: -1.99 to 0.13; Pâ=â0.08). However, this estimate was highly sensitive to the inclusion of the recent very large PANORAMIC trial. Omitting this outlier, half the variation in clinical benefit (R2â=â50.4%) was explained by variation in VCRRs [slope -1.47 (95% CI -2.43 to -0.51); Pâ=â0.003], i.e. higher VCRRs were associated with an increased clinical benefit. CONCLUSION: Methods of determining viral clearance in COVID-19 studies and the relationship to clinical outcomes vary greatly. As prohibitively large sample sizes are now required to show clinical treatment benefit in antiviral therapeutic assessments, viral clearance is a reasonable surrogate endpoint.
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Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Progressão da Doença , SARS-CoV-2 , Humanos , COVID-19/virologia , Antivirais/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Carga Viral/efeitos dos fármacos , Resultado do Tratamento , HospitalizaçãoRESUMO
OBJECTIVE: The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year. To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. METHODS: 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. RESULTS: 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively. CONCLUSIONS: Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.
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Doenças da Aorta , Dissecção Aórtica , Síndrome de Turner , Adulto , Feminino , Humanos , Adolescente , Adulto Jovem , Síndrome de Turner/complicações , Síndrome de Turner/epidemiologia , Estudos Retrospectivos , Doenças da Aorta/complicações , Doenças da Aorta/epidemiologia , Medição de RiscoRESUMO
In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance. BACKGROUND: Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries. METHODS: In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log10 viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13/09/2021. RESULTS: In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated. INTERPRETATION: Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied patients.
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Amidas , COVID-19 , Pirazinas , Adulto , Humanos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento , Antivirais/uso terapêuticoRESUMO
OBJECTIVES: For many people with dementia and unpaid carers, using technology for care and support has become essential. Rapid proliferation of technology highlights the need to understand digital access to health and social care services for dementia. This mixed-methods systematic review aims to explore digital access to health and social care services for dementia, from the perspective of people with dementia and unpaid carers. METHODS: Nine electronic databases were searched in May 2023 for qualitative, quantitative, or mixed-method studies, published in English or German, focused on experiences of using technology-delivered health and social care services for people with dementia and unpaid carers. After removal of duplicates and screening, 44 empirical papers were included. RESULTS: From the 44 studies, findings were grouped into five categories, highlighting experiences for people with dementia and unpaid carers: (1) Adapting to technology, (2) Inequalities and variations in outcomes, (3) Impact on caring, (4) Impact on health, and (5) Impact on relationships. Proliferation of technology in care access emphasised the need for quick adaptation to technology and examination of its impact. The impact of such service delivery has evidenced mixed findings. There were improvements in the health and wellbeing of people with dementia and unpaid carers, and benefits for their dyadic relationship. However, using technology for health and social care access is not always possible and is often reliant on unpaid carers for support. Lower tech-literacy, lack of equipment or money to buy equipment and poor internet connection can impact the potential for positive outcomes. CONCLUSIONS: Technology can bring great benefits: social inclusion, improved service access and care. However, using technology in service delivery in dementia needs careful thought. Professionals and service providers need to be cognizant of the complex nature of dementia, and the benefits and challenges of hybrid service delivery.
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Cuidadores , Demência , Acessibilidade aos Serviços de Saúde , Humanos , Demência/terapia , Demência/diagnóstico , Serviço Social , TelemedicinaRESUMO
BACKGROUND: The number of people living with dementia (PLWD) continues to increase, particularly those with severe symptomatology. Severe symptoms and greater ill-health result in more acute care need. Early healthcare interventions can prove beneficial. Healthcare use has not been analysed as a holistic set of interlinked events. This study explores different healthcare pathways among PLWD, social or spatial inequalities in healthcare pathways and subsequent mortality risk. METHODS: Group-based trajectory models (GBTM) were applied to electronic healthcare records. We generated clusters of PLWD with similar five-year, post-diagnosis trajectories in rates of primary and secondary healthcare use. Potential social and spatial variations in healthcare use clusters were examined. Cox Proportional Hazards used to explore variation in subsequent mortality risk between healthcare use clusters. RESULTS: Four healthcare use clusters were identified in both early- (n = 3732) and late-onset (n = 6224) dementia populations. Healthcare use variations were noted; consistent or diminishing healthcare use was associated with lower subsequent mortality risk. Increasing healthcare use was associated with increased mortality risk. Descriptive analyses indicated social and spatial variation in healthcare use cluster membership. CONCLUSION: Healthcare pathways can help indicate changing need and variation in need, with differential patterns in initial healthcare use post-diagnosis, producing similar subsequent mortality risk. Care in dementia needs to be more accessible and appropriate, with care catered to specific and changing needs. Better continuity of care and greater awareness of dementia in primary can enhance prospects for PLWD. Research needs to further illuminate holistic care need for PLWD, including health and social care use, inequalities in care, health and outcomes.
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Demência , Humanos , Demência/diagnóstico , Demência/epidemiologia , Demência/terapia , Atenção à Saúde , Instalações de Saúde , Apoio Social , Inglaterra/epidemiologia , CuidadoresRESUMO
Climate shocks can reorganize the social-ecological linkages in food-producing communities, leading to a sudden loss of key products in food systems. The extent and persistence of this reorganization are difficult to observe and summarize, but are critical aspects of predicting and rapidly assessing community vulnerability to extreme events. We apply network analysis to evaluate the impact of a climate shock-an unprecedented marine heatwave-on patterns of resource use in California fishing communities, which were severely affected through closures of the Dungeness crab fishery. The climate shock significantly modified flows of users between fishery resources during the closures. These modifications were predicted by pre-shock patterns of resource use and were associated with three strategies used by fishing community member vessels to respond to the closures: temporary exit from the food system, spillover of effort from the Dungeness crab fishery into other fisheries, and spatial shifts in where crab were landed. Regional differences in resource use patterns and vessel-level responses highlighted the Dungeness crab fishery as a seasonal "gilded trap" for northern California fishing communities. We also detected disparities in climate shock response based on vessel size, with larger vessels more likely to display spatial mobility. Our study demonstrates the importance of highly connected and decentralized networks of resource use in reducing the vulnerability of human communities to climate shocks.
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Mudança Climática/economia , Conservação dos Recursos Naturais/métodos , Pesqueiros/tendências , Animais , Braquiúros , Clima , Mudança Climática/estatística & dados numéricos , Conservação dos Recursos Naturais/tendências , Ecossistema , Pesqueiros/economia , Humanos , Alimentos Marinhos , Frutos do Mar , Estados UnidosRESUMO
Archaeological and paleoecological evidence shows that by 10,000 BCE, all human societies employed varying degrees of ecologically transformative land use practices, including burning, hunting, species propagation, domestication, cultivation, and others that have left long-term legacies across the terrestrial biosphere. Yet, a lingering paradigm among natural scientists, conservationists, and policymakers is that human transformation of terrestrial nature is mostly recent and inherently destructive. Here, we use the most up-to-date, spatially explicit global reconstruction of historical human populations and land use to show that this paradigm is likely wrong. Even 12,000 y ago, nearly three quarters of Earth's land was inhabited and therefore shaped by human societies, including more than 95% of temperate and 90% of tropical woodlands. Lands now characterized as "natural," "intact," and "wild" generally exhibit long histories of use, as do protected areas and Indigenous lands, and current global patterns of vertebrate species richness and key biodiversity areas are more strongly associated with past patterns of land use than with present ones in regional landscapes now characterized as natural. The current biodiversity crisis can seldom be explained by the loss of uninhabited wildlands, resulting instead from the appropriation, colonization, and intensifying use of the biodiverse cultural landscapes long shaped and sustained by prior societies. Recognizing this deep cultural connection with biodiversity will therefore be essential to resolve the crisis.
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Agricultura/história , Biodiversidade , Conservação dos Recursos Naturais/história , Povos Indígenas/história , Natureza , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , História Medieval , Migração Humana , HumanosRESUMO
BACKGROUND: Uncertainty over the therapeutic benefit of parenteral remdesivir in coronavirus disease 2019 (COVID-19) has resulted in varying treatment guidelines. METHODS: In a multicenter open-label, controlled, adaptive, pharmacometric platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to 1 of 8 treatment arms including intravenous remdesivir (200 mg followed by 100 mg daily for 5 days) or no study drug. The primary outcome was the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance (estimated under a linear model fit to the daily log10 viral densities, days 0-7) in standardized duplicate oropharyngeal swab eluates, in a modified intention-to-treat population. This ongoing adaptive trial is registered at ClinicalTrials.gov (NCT05041907). RESULTS: The 2 study arms enrolled 131 patients (remdesivir n = 67, no study drug n = 64) and estimated viral clearance rates from a median of 18 swab samples per patient (a total of 2356 quantitative polymerase chain reactions). Under the linear model, compared with the contemporaneous control arm (no study drug), remdesivir accelerated mean estimated viral clearance by 42% (95% credible interval, 18%-73%). CONCLUSIONS: Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Pharmacometric assessment of therapeutics using the method described can determine in vivo clinical antiviral efficacy rapidly and efficiently.
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COVID-19 , Adulto , Humanos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento , AntiviraisRESUMO
Avian paramyxovirus type 1 (APMV-1) is a virus of birds that results in a range of outcomes, from asymptomatic infections to outbreaks of systemic respiratory and neurologic disease, depending on the virus strain and the avian species affected. Humans are rarely affected; those who are predominantly experience mild conjunctivitis. We report a fatal case of neurologic disease in a 2-year-old immunocompromised child in Australia. Metagenomic sequencing and histopathology identified the causative agent as the pigeon variant of APMV-1. This diagnosis should be considered in neurologic conditions of undefined etiologies. Agnostic metagenomic sequencing methods are useful in such settings to direct diagnostic and therapeutic efforts.
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Doenças Transmissíveis , Doença de Newcastle , Animais , Pré-Escolar , Humanos , Austrália/epidemiologia , Columbidae , Doença de Newcastle/epidemiologia , Doença de Newcastle/patologia , Vírus da Doença de Newcastle , FilogeniaRESUMO
In this Policy Forum article, James A. Watson and colleagues discuss recent guidelines relating to pre-referral treatment of suspected severe malaria with rectal artesunate suppositories in remote areas.
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Antimaláricos , Artemisininas , Malária , Humanos , Artesunato/uso terapêutico , Antimaláricos/uso terapêutico , Supositórios , Artemisininas/uso terapêutico , Malária/tratamento farmacológico , Encaminhamento e ConsultaRESUMO
BACKGROUND: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials. METHODS: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality. RESULTS: The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine. CONCLUSIONS: Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).
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Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Betacoronavirus , COVID-19 , Infecções por Coronavirus/mortalidade , Feminino , Hospitalização , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Respiração Artificial , SARS-CoV-2 , Falha de Tratamento , Tratamento Farmacológico da COVID-19RESUMO
CARAMAL was a large observational study which recorded mortality in children with suspected severe malaria before and after the roll-out of rectal artesunate in Nigeria, Uganda and the Democratic Republic of the Congo. The results of CARAMAL have had a huge impact on public health policy leading to a World Health Organization moratorium on the roll-out of rectal artesunate. The conclusion reported in the abstract uses strong causal language, stating that "pre-referral RAS [rectal artesunate suppositories] had no beneficial effect on child survival". We argue that this causal interpretation of the study results is not justified. Data from the CARAMAL study inform chiefly on the strengths and weaknesses of referral systems in these three countries and do not inform reliably as to the beneficial effect of providing access to a known life-saving treatment.