Showing papers by "Steven N. Goodman published in 2023"

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Abstract: Importance SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure SARS-CoV-2 infection. Main Outcomes and Measures PASC and 44 participant-reported symptoms (with severity thresholds). Results A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Race and Ethnicity Reporting and Representation in Pediatric Clinical Trials.

Abstract: BACKGROUND AND OBJECTIVES Representative enrollment of racial and ethnic minoritized populations in biomedical research ensures the generalizability of results and equitable access to novel therapies. Previous studies on pediatric clinical trial diversity are limited to subsets of journals or disciplines. We aimed to evaluate race and ethnicity reporting and representation in all US pediatric clinical trials on ClinicalTrials.gov. METHODS We performed a cross-sectional study of US-based clinical trials registered on ClinicalTrials.gov that enrolled participants aged <18 years old between October 2007 and March 2020. We used descriptive statistics, compound annual growth rates, and multivariable logistic regression for data analysis. Estimates of US population statistics and disease burden were calculated with the US Census, Kids' Inpatient Database, and National Survey of Children's Health. RESULTS Among 1183 trials encompassing 405 376 participants, race and ethnicity reporting significantly increased from 27% in 2007 to 87% in 2018 (P < .001). The median proportional enrollment of Asian American children was 0.6% (interquartile range [IQR], 0%-3.7%); American Indian, 0% (IQR, 0%-0%); Black, 12% (IQR, 2.9%-28.4%); Hispanic, 7.1% (IQR, 0%-18.6%); and white 66.4% (IQR, 41.5%-81.6%). Asian American, Black, and Hispanic participants were underrepresented relative to US population demographics. Compared with expected proportions based on disease prevalence and hospitalizations, Asian American and Hispanic participants were most consistently underrepresented across diagnoses. CONCLUSIONS While race and ethnicity reporting in pediatric clinical trials has improved, the representative enrollment of minoritized participants remains an ongoing challenge. Evidence-based and policy solutions are needed to address these disparities to advance biomedical innovation for all children.

A Maximum Entropy Species Distribution Model to Estimate the Distribution of Bushpigs on Madagascar and Its Implications for African Swine Fever

Abstract: Bushpigs (Potamochoerus larvatus) play a major role in the socio-ecosystem of Madagascar, particularly in rural areas. They are largely hunted by rural populations as a major source of income and protein. They can also represent a potential source of pathogens for domestic animals and people. For example, it is hypothesized that bushpigs might compromise African swine fever (ASF) eradication programs by sporadically transmitting the virus to domestic pigs. However, available knowledge on the distribution of bushpigs in Madagascar is limited. In this study, we estimated the distribution of bushpigs on Madagascar using a species distribution model (SDM). We retrieved 206 sightings of bushpigs in Madagascar during 1990–2016 and predicted the distribution by using 37 climatic, geographic, and agricultural/human variables related to the presence of bushpigs and running a presence-background maximum entropy SDM. Our model identified three main areas with a high suitability for bushpigs: in the north, central-western, and east of the island (AUC = 0.84). The main contributors to the model were the vegetation index (51.3%), percentage of land covered by trees (17.6%), and annual averaged monthly precipitation (12.6%). In addition, we identified areas in central Madagascar with a high density of domestic pigs and a high suitability score for bushpigs. These results may help to identify bushpig areas at the interface with domestic pigs to assess the risk of pathogen transmission and to design ecological assessments, wildlife management studies, or targeted surveillance and research studies related to many bushpig-borne pathogens, such as ASF, which is an endemic problem in the country, as well as zoonotic diseases such as cysticercosis and hepatitis E. Our approach could also be extrapolated to other species of wild swine in other countries.

Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design

Abstract: Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged [≥]18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

Ancestral African Bats Brought Their Cargo of Pathogenic Leptospira to Madagascar under Cover of Colonization Events

Abstract: Madagascar is home to an extraordinary diversity of endemic mammals hosting several zoonotic pathogens. Although the African origin of Malagasy mammals has been addressed for a number of volant and terrestrial taxa, the origin of their hosted zoonotic pathogens is currently unknown. Using bats and Leptospira infections as a model system, we tested whether Malagasy mammal hosts acquired these infections on the island following colonization events, or alternatively brought these bacteria from continental Africa. We first described the genetic diversity of pathogenic Leptospira infecting bats from Mozambique and then tested through analyses of molecular variance (AMOVA) whether the genetic diversity of Leptospira hosted by bats from Mozambique, Madagascar and Comoros is structured by geography or by their host phylogeny. This study reveals a wide diversity of Leptospira lineages shed by bats from Mozambique. AMOVA strongly supports that the diversity of Leptospira sequences obtained from bats sampled in Mozambique, Madagascar, and Comoros is structured according to bat phylogeny. Presented data show that a number of Leptospira lineages detected in bat congeners from continental Africa and Madagascar are imbedded within monophyletic clades, strongly suggesting that bat colonists have indeed originally crossed the Mozambique Channel while infected with pathogenic Leptospira.

Influence of Environmental Parameters on the Breeding of an Endemic Malagasy Fruit Bat, Rousettus madagascariensis (Pteropodidae)

Abstract: The breeding biology of bats is in part regulated by environmental parameters, which in certain cases result in considerable intraspecific variation in reproduction periods. Few details are available on the reproductive behavior of Malagasy bats and this study focuses on parameters related to the mating and parturition periods in the endemic frugivorous and cave-roosting Rousettus madagascariensis (Pteropodidae). The birth period was estimated based on observations of mating behavior and presence of neonates in video recordings made at Ankarana (northern Madagascar) during different seasonal periods in 2017 and 2018. Based on animals captured in the same cave between 2014 and 2022, we also estimated the age of neonates in order to evaluate annual variation in parturition periodicity. Based on video recordings, mating was mainly observed (ordered based on highest frequency) in September, July, and January. This behavior, which generally took place during the dry season, was negatively correlated with temperature and rainfall, and had a low positive correlation with cave relative humidity. With most mating taking place between July and September, one parturition period occurs just before or during the wet season (between December and February), the period of highest fruit abundance in Ankarana. For cases of mating in January, excluding the possibility of sperm storage or delayed implantation, another parturition would occur in mid-April, a time of low fruit availability; however, no neonate was filmed or trapped in April and video recording data indicated that neonates were present between July and September, suggesting a parturition taking place from July to September. Parturition periods show some annual variation and appear to be mainly regulated by climatic aspects including rainfall and principally temperature; however, this variation was less pronounced as compared to other non-Malagasy pteropodid species. Further research on Malagasy fruit bats should focus on possible sperm storage or delayed embryonic development and, if found, associated correlations with environmental parameters.

[In the wake of the replication crisis, reproducibility networks take action against widespread methodological shortcomings].

Abstract: The »replication crisis« refers to the crisis of confidence triggered by the failure to reproduce a large portion of important findings in several scientific disciplines, including medicine. Failed replication occurred in high-profiled scandals such as the »omics« case at Duke University, as well as in systematic attempts to reproduce influential preclinical studies. An extensive meta-research literature attests to problems with suboptimal methods choices and indicates that behaviors bordering between deliberate misleading and well-intentioned mistakes (questionable research practices) are very common (e.g. selective reporting of particular results »based on a gut feeling«). As a consequence, influential international institutions have been prompted to take action to strengthen research rigor and reproducibility. So-called reproducibility networks, pioneered in the UK, seem particularly promising to organize necessary coordinated efforts among a wide range of stakeholders.

Aperçu sur la fragmentation de la forêt naturelle dans la Réserve Spéciale d’Ambohitantely et ses alentours entre 1949 et 2017, Hautes Terres Centrales

Abstract: Cette étude vise à caractériser la dynamique de la couverture forestière et la fragmentation de la forêt naturelle de la Réserve Spéciale d’Ambohitantely et les zones périphériques dans un rayon de 10 km de la limite de l’aire protégée entre 1949 et 2017. Au total, cinq images satellitaires pour les années 1989, 1995, 2002, 2010 et 2017, et 59 clichés de photographies aériennes prises en 1949 ont été utilisées. La télédétection et le système d’information géographique ont été utilisés pour la cartographie de l’occupation du sol pour les six périodes d’études, ainsi que pour l’analyse de la dynamique de la couverture forestière et l’estimation de la perte de surface forestière. Six métriques disponibles sur le logiciel FRAGSTATS ont été sélectionnées pour l’analyse de la fragmentation à l’échelle du paysage à savoir, le nombre de parcelles (NP), la densité de parcelles (PD), la variabilité de la taille des parcelles (AREA_SD), l’indice de la dimension fractale (FRAC_MN), l’indice de contiguïté (CONTIG_MN) et l’indice d’agrégation (AI). Après une classification supervisée, les classes d’occupation du sol ont été reclassées en forêt ou non-forêt. La dynamique de la couverture forestière dans la zone étudiée a montré qu’une vaste zone forestière a été convertie en zone non forestière. L’estimation de la perte de forêt indique que le taux annuel dans la réserve varie, et la plus importante estimée à 586,4 ha soit 4,05% par an a été enregistrée entre 1995 et 2002, et la plus faible est de 473,4 ha soit 0,41% par an, entre 1949 et 1989. Les résultats ont montré la diminution du nombre de fragments ainsi que la densité des fragments depuis 1989 à 2017, ce qui indique la disparition de fragments forestiers. En parallèle, la réduction de l’indice de la dimension fractale et de la variabilité de la taille des parcelles révèlent la simplification de la forme des fragments et la faible diversification de la superficie des différents fragments. L’augmentation de l’indice d’agrégation contre la diminution de l’indice de contiguïté confirme l’isolement des fragments. This study aims to characterize the dynamics of forest cover and fragmentation of the natural forest of the Ambohitantely Special Reserve between 1949 and 2017 and within a radius of 10 km of the boundary limit. Five different periods of satellite images were employed, specifically the years 1989, 1995, 2002, 2010, and 2017, as well as aerial photographs taken in 1949. Remote sensing and geographic information systems were used for land cover mapping for the six study periods, as well as for analyzing forest cover dynamics and estimating forest cover loss. Using the software FRAGSTATS, six different metrics were selected for the analysis of forest fragmentation at the landscape level: number of patches (NP), patch density (PD), patch size standard deviation (AREA_SD), mean patch fractal dimension (FRAC_MN), contiguity index (CONTIG_MN), and aggregation index (AI). Following a supervised classification, land cover classes were reclassified as forest or non-forest. The dynamics of forest cover at the site and over the study period indicated that considerable zones of forest were transformed to non-forested areas. The estimate of forest loss indicates that the annual rate in the reserve varies, and the largest estimated at 586.4 ha or 4.05% per year was recorded between 1995 and 2002, and the lowest is 473.4 ha or 0.41% between 1949 and 1989. The results indicate a decrease in the number of fragments as well as the density of fragments from 1989 to 2017 associated with the disappearance of forest. In parallel, the reduction of the mean patch fractal dimension and variability of the patch size denotes the simplification of the fragments’ shapes and the slight diversification of the areas of the different fragments. An increase in the aggregation index as compared to a decrease in the contiguity index confirms the isolation of the fragments.

Stuck on a small tropical island: wide in-situ diversification of an urban-dwelling bat

Abstract: Bats are often the only mammals naturally colonizing isolated islands and are thus an excellent model to study evolutionary processes of insular ecosystems. Here, we studied the Reunion free-tailed bat (Mormopterus francoismoutoui), an endemic species to Reunion Island that has adapted to urban settings. At regional scale, we investigated the evolutionary history of Mormopterus species, as well as on Reunion Island sex-specific and seasonal patterns of genetic structure. We used an extensive spatio-temporal sampling including 1,136 individuals from 18 roosts and three biological seasons (non-reproductive/winter, pregnancy/summer, and mating), with additional samples from Mormopterus species from neighbouring islands (M. jugularis of Madagascar and M. acetabulosus of Mauritius). Complementary information gathered from both microsatellite and mitochondrial markers revealed a high genetic diversity but no signal of spatial genetic structure and weak evidence of female philopatry. Regional analysis suggests a single colonization event for M. francoismoutoui, dated around 175,000 years ago, and followed by in-situ diversification and the evolution of divergent ancestral lineages, which today form a large metapopulation. Population expansion was relatively ancient (55,000 years ago) and thus not linked to human colonization of the island and the availability of new anthropic day-roost sites. Discordant structure between mitochondrial and microsatellite markers suggests the presence of yet-unknown mating sites, or the recent evolution of putative ecological adaptations. Our study illustrates how understanding mechanisms involved in speciation can be challenging and the importance of both mitochondrial and nuclear DNA in resolving the wide in-situ diversification of an urban-dwelling bat, endemic to a small island.

“Easier or Harder, Depending on Who the Hearing Person Is”: Codesigning Videoconferencing Tools for Small Groups with Mixed Hearing Status

Abstract: With improvements in automated speech recognition and increased use of videoconferencing, real-time captioning has changed significantly. This shift toward broadly available but less accurate captioning invites exploration of the role hearing conversation partners play in shaping the accessibility of a conversation to d/Deaf and hard of hearing (DHH) captioning users. While recent work has explored DHH individuals’ videoconferencing experiences with captioning, we focus on established groups’ current practices and priorities for future tools to support more accessible online conversations. Our study consists of three codesign sessions, conducted with four groups (17 participants total, 10 DHH, 7 hearing). We found that established groups crafted social accessibility norms that met their relational contexts. We also identify promising directions for future captioning design, including the need to standardize speaker identification and customization, opportunities to provide behavioral feedback during a conversation, and ways that videoconferencing platforms could enable groups to set and share norms.

Seeing the Positive in Negative Studies

Abstract: Identifying ineffective health interventions can be as important as identifying effective ones (1). Consequently, Annals is interested in publishing “negative” studies. We base our editorial decisions not on the “positivity” of findings (that is, their statistical significance) but on the importance of the research question and methodological quality. Unfortunately, few negative studies provide strong evidence for treatment ineffectiveness (2). To do so, they must have results statistically compatible only with a narrow range of small effects. If we can exclude sources of bias and agree that clinically important effects lie outside this range, we can conclude that the intervention is clinically ineffective. Although it is impossible to “prove” a null hypothesis of no effect, such studies provide strong evidence that any nonzero effect of the intervention is unlikely to be clinically meaningful. Many negative studies, however, are imprecise, and their results are compatible with a wide range of effects, thereby providing weak evidence that the intervention is clinically ineffective. Regrettably, imprecise results whose margin of error (represented by their CIs) include a null effect are often misinterpreted as providing strong evidence of ineffectiveness. In their article, Wang and colleagues (3) provide a good example of properly interpreting a negative study. These investigators conducted a randomized clinical trial (ACTIV-4C [COVID-19 Thrombosis Prevention Trials: Post-hospital Thromboprophylaxis]) to evaluate the effect of extended thromboprophylaxis in patients hospitalized for COVID-19 in 107 U.S. hospitals. Patients were randomly assigned to 2.5 mg of apixaban or placebo twice daily at hospital discharge and continued treatment for 30days. The primary end point was a composite of all-cause mortality, venous thrombosis, and arterial thrombosis within 30days of randomization. On the basis of the assumptions that 4% of patients in the placebo group would develop the primary end point and that apixaban would have an efficacy of 35%, the investigators estimated that they needed 5320 patients (2660 in each group) to reliably evaluate the efficacy of the intervention. ACTIV-4C began recruitment on 15 February 2021. The study’s data and safety monitoring board met on 15 June 2022 and noted that the rate of the primary end point was lower than anticipated and that the waning of COVID-19 hospitalizations in the United States would make achieving recruitment targets difficult. On 21 June 2022, study leadership and the National Heart, Lung, and Blood Institute decided to halt new enrollment while continuing treatment and observation of the 1217 patients enrolled through 23 June 2023. At completion of follow-up, only 27 participants experienced a primary end point (14 in the placebo group and 13 in the treatment group). The relative risk for the primary end point comparing thromboprophylaxis with placebo was 0.92 (95% CI, 0.44 to 1.95; P = 0.85). A simplistic interpretation of such negative findings is that thromboprophylaxis was ineffective. A proper interpretation would be more nuanced. The risk for allcause mortality, venous thrombosis, and/or arterial thrombosis after discharge was lower than anticipated. In the placebo group, the 30-day cumulative incidence of the combined end point was only 2.31%, including 5 cases of venous thromboembolism (0.82%) and 3 cases of arterial thromboembolism (0.49%). The risk for these end points in hospitalized patients with COVID-19 was similar to that in other medically ill hospitalized patients (4), and the potential absolute benefit of thromboprophylaxis in this setting is small. The lower than anticipated event rate and the inability to reach target sample size meant that the treatment effect was too imprecisely estimated to conclude that the treatment was clinically ineffective. Wang and colleagues stated that the results were imprecise and “highly compatible, with estimates of efficacy ranging from a 56% reduction to a 95% increase in risk for apixaban compared with placebo.” Such descriptions should be routine when reporting negative studies (Table). The 95% CI represents the range of true effects consistent with the observed effect based only on random variability—that is, if the estimate is unbiased (2, 5). A wide CI around a null effect indicates that the data are statistically compatible with a wide range of effects—from harm to no effect to benefit. How narrow should the CI be to conclude that an intervention is clinically ineffective? That depends on the size of effects considered clinically important. Researchers should refrain from identifying findings as negative or positive. Instead, they should clearly state the range of effects compatible with the observed data and help the reader to determine if the results are compatible with clinically meaningful effects. Focusing on the clinical implications of confidence bounds further underscores the need for careful study design and correct variance estimation (6). This problem is hardly new (2, 7, 8), but the situation has been hard to change. In 1978, Freiman and colleagues (7) evaluated 71 published trials whose investigators concluded that the test intervention was not superior to control. Many of these studies had 95% CIs compatible with clinically important beneficial and