Antibiotic prophylaxis for leptospirosis.

BACKGROUND: Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3). OBJECTIVES: To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis. SEARCH METHODS: We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023. SELECTION CRITERIA: We included ⁠⁠randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. MAIN RESULTS: We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source. AUTHORS' CONCLUSIONS: We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.

Antibiotics for treatment of leptospirosis.

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.

Correction: Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

[This corrects the article DOI: 10.1371/journal.pmed.1003793.].

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Recommended reporting items for epidemic forecasting and prediction research: The EPIFORGE 2020 guidelines.

BACKGROUND: The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. METHODS AND FINDINGS: We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. CONCLUSIONS: These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

Mitigating a COVID-19 Outbreak Among Major League Baseball Players - United States, 2020.

Mass gatherings have been implicated in higher rates of transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), and many sporting events have been restricted or canceled to limit disease spread (1). Based on current CDC COVID-19 mitigation recommendations related to events and gatherings (2), Major League Baseball (MLB) developed new health and safety protocols before the July 24 start of the 2020 season. In addition, MLB made the decision that games would be played without spectators. Before a three-game series between teams A and B, the Philadelphia Department of Public Health was notified of a team A player with laboratory-confirmed COVID-19; the player was isolated as recommended (2). During the series and the week after, laboratory-confirmed COVID-19 was diagnosed among 19 additional team A players and staff members and one team B staff member. Throughout their potentially infectious periods, some asymptomatic team A players and coaches, who subsequently received positive SARS-CoV-2 test results, engaged in on-field play with teams B and C. No on-field team B or team C players or staff members subsequently received a clinical diagnosis of COVID-19. Certain MLB health and safety protocols, which include frequent diagnostic testing for rapid case identification, isolation of persons with positive test results, quarantine for close contacts, mask wearing, and social distancing, might have limited COVID-19 transmission between teams.

Remediation of PFAS-Contaminated Soil and Granular Activated Carbon by Smoldering Combustion.

This study explored smoldering combustion for remediating polyfluoroalkyl substance (PFAS)-impacted granular activated carbon (GAC) and PFAS-contaminated soil. GAC, both fresh and PFAS-loaded, was employed as the supplemental fuel supporting smoldering in mixtures with sand (≈175 mg PFAS/kg GAC-sand), with PFAS-spiked, laboratory-constructed soil (≈4 mg PFAS/kg soil), and with a PFAS-impacted field soil (≈0.2 mg PFAS/kg soil). The fate of PFAS and fluorine was quantified with soil and emission analyses, including targeted PFAS and suspect screening as well as hydrogen fluoride and total fluorine. Results demonstrated that exceeding 35 g GAC/kg soil resulted in self-sustained smoldering with temperatures exceeding 900 °C. Post-treatment PFAS concentrations of the treated soil were near (2 experiments) or below (7 experiments) detection limits (0.0004 mg/kg). Further, 44% of the initial PFAS on GAC underwent full destruction, compared to 16% of the PFAS on soil. Less than 1% of the initial PFAS contamination on GAC or soil was emitted as PFAS in the quantifiable analytical suite. Results suggest that the rest were emitted as altered, shorter-chain PFAS and volatile fluorinated compounds, which were scrubbed effectively with GAC. Total organic fluorine analysis proved useful for PFAS-loaded GAC in sand; however, analyzing soils suffered from interference from non-PFAS. Overall, this study demonstrated that smoldering has significant potential as an effective remediation technique for PFAS-impacted soils and PFAS-laden GAC.

Evidence-based guidelines for supportive care of patients with Ebola virus disease.

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.

Clinical presentation of patients with Ebola virus disease in Conakry, Guinea.

BACKGROUND: In March 2014, the World Health Organization was notified of an outbreak of Zaire ebolavirus in a remote area of Guinea. The outbreak then spread to the capital, Conakry, and to neighboring countries and has subsequently become the largest epidemic of Ebola virus disease (EVD) to date. METHODS: From March 25 to April 26, 2014, we performed a study of all patients with laboratory-confirmed EVD in Conakry. Mortality was the primary outcome. Secondary outcomes included patient characteristics, complications, treatments, and comparisons between survivors and nonsurvivors. RESULTS: Of 80 patients who presented with symptoms, 37 had laboratory-confirmed EVD. Among confirmed cases, the median age was 38 years (interquartile range, 28 to 46), 24 patients (65%) were men, and 14 (38%) were health care workers; among the health care workers, nosocomial transmission was implicated in 12 patients (32%). Patients with confirmed EVD presented to the hospital a median of 5 days (interquartile range, 3 to 7) after the onset of symptoms, most commonly with fever (in 84% of the patients; mean temperature, 38.6°C), fatigue (in 65%), diarrhea (in 62%), and tachycardia (mean heart rate, >93 beats per minute). Of these patients, 28 (76%) were treated with intravenous fluids and 37 (100%) with antibiotics. Sixteen patients (43%) died, with a median time from symptom onset to death of 8 days (interquartile range, 7 to 11). Patients who were 40 years of age or older, as compared with those under the age of 40 years, had a relative risk of death of 3.49 (95% confidence interval, 1.42 to 8.59; P=0.007). CONCLUSIONS: Patients with EVD presented with evidence of dehydration associated with vomiting and severe diarrhea. Despite attempts at volume repletion, antimicrobial therapy, and limited laboratory services, the rate of death was 43%.

Costs and consequences: Hepatitis C seroprevalence in the military and its impact on potential screening strategies.

UNLABELLED: Knowledge of the contemporary epidemiology of hepatitis C viral (HCV) infection among military personnel can inform potential Department of Defense screening policy. HCV infection status at the time of accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period 2007-2010. A cost model was developed from the perspective of the Department of Defense for a military applicant screening program. Return on investment was based on comparison between screening program costs and potential treatment costs avoided. The prevalence of HCV antibody-positive and chronic HCV infection at accession among younger recently deployed military personnel born after 1965 was 0.98/1000 (95% confidence interval 0.45-1.85) and 0.43/1000 (95% confidence interval 0.12-1.11), respectively. Among these, service-related incidence was low; 64% of infections were present at the time of accession. With no screening, the cost to the Department of Defense of treating the estimated 93 cases of chronic HCV cases from a single year's accession cohort was $9.3 million. Screening with the HCV antibody test followed by the nucleic acid test for confirmation yielded a net annual savings and a $3.1 million dollar advantage over not screening. CONCLUSIONS: Applicant screening will reduce chronic HCV infection in the force, result in a small system costs savings, and decrease the threat of transfusion-transmitted HCV infection in the battlefield blood supply and may lead to earlier diagnosis and linkage to care; initiation of an applicant screening program will require ongoing evaluation that considers changes in the treatment cost and practice landscape, screening options, and the epidemiology of HCV in the applicant/accession and overall force populations.

Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014-2015.

BACKGROUND: Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014-2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. METHODS: We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. RESULTS: From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. CONCLUSIONS: The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community.

Ebola virus disease and critical illness.

As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa.EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.Males and females have been equally affected, with children (0-14 years of age) accounting for 19 %, young adults (15-44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40-90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes.

Smoldering Remediation of Coal-Tar-Contaminated Soil: Pilot Field Tests of STAR.

Self-sustaining treatment for active remediation (STAR) is an emerging, smoldering-based technology for nonaqueous-phase liquid (NAPL) remediation. This work presents the first in situ field evaluation of STAR. Pilot field tests were performed at 3.0 m (shallow test) and 7.9 m (deep test) below ground surface within distinct lithological units contaminated with coal tar at a former industrial facility. Self-sustained smoldering (i.e., after the in-well ignition heater was terminated) was demonstrated below the water table for the first time. The outward propagation of a NAPL smoldering front was mapped, and the NAPL destruction rate was quantified in real time. A total of 3700 kg of coal tar over 12 days in the shallow test and 860 kg over 11 days in the deep test was destroyed; less than 2% of total mass removed was volatilized. Self-sustaining propagation was relatively uniform radially outward in the deep test, achieving a radius of influence of 3.7 m; strong permeability contrasts and installed barriers influenced the front propagation geometry in the shallow test. Reductions in soil hydrocarbon concentrations of 99.3% and 97.3% were achieved in the shallow and deep tests, respectively. Overall, this provides the first field evaluation of STAR and demonstrates that it is effective in situ and under a variety of conditions and provides the information necessary for designing the full-scale site treatment.

Caring for critically ill patients with ebola virus disease. Perspectives from West Africa.

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.

Geroscience and pathology: a new frontier in understanding age-related diseases.

Geroscience, a burgeoning discipline at the intersection of aging and disease, aims to unravel the intricate relationship between the aging process and pathogenesis of age-related diseases. This paper explores the pivotal role played by geroscience in reshaping our understanding of pathology, with a particular focus on age-related diseases. These diseases, spanning cardiovascular and cerebrovascular disorders, malignancies, and neurodegenerative conditions, significantly contribute to the morbidity and mortality of older individuals. We delve into the fundamental cellular and molecular mechanisms underpinning aging, including mitochondrial dysfunction and cellular senescence, and elucidate their profound implications for the pathogenesis of various age-related diseases. Emphasis is placed on the importance of assessing key biomarkers of aging and biological age within the realm of pathology. We also scrutinize the interplay between cellular senescence and cancer biology as a central area of focus, underscoring its paramount significance in contemporary pathological research. Moreover, we shed light on the integration of anti-aging interventions that target fundamental aging processes, such as senolytics, mitochondria-targeted treatments, and interventions that influence epigenetic regulation within the domain of pathology research. In conclusion, the integration of geroscience concepts into pathological research heralds a transformative paradigm shift in our understanding of disease pathogenesis and promises breakthroughs in disease prevention and treatment.

Trends in prevalence, mortality, and risk factors of dementia among the oldest-old adults in the United States: the role of the obesity epidemic.

The oldest-old population, those aged ≥ 80 years, is the fastest-growing group in the United States (US), grappling with an increasingly heavy burden of dementia. We aimed to dissect the trends in dementia prevalence, mortality, and risk factors, and predict future levels among this demographic. Leveraging data from the Global Burden of Disease Study 2019, we examined the trends in dementia prevalence, mortality, and risk factors (with a particular focus on body mass index, BMI) for US oldest-old adults. Through decomposition analysis, we identified key population-level contributors to these trends. Predictive modeling was employed to estimate future prevalence and mortality levels over the next decade. Between 1990 and 2019, the number of dementia cases and deaths among the oldest-old in the US increased by approximately 1.37 million and 60,000 respectively. The population growth and aging were highlighted as the primary drivers of this increase. High BMI emerged as a growing risk factor. Females showed a disproportionately higher dementia burden, characterized by a unique risk factor profile, including BMI. Predictions for 2030 anticipate nearly 4 million dementia cases and 160,000 related deaths, with a marked increase in prevalence and mortality anticipated among those aged 80-89. The past 30 years have witnessed a notable rise in both the prevalence and mortality of dementia among the oldest-old in the US, accompanied by a significant shift in risk factors, with obesity taking a forefront position. Targeted age and sex-specific public health strategies that address obesity control are needed to mitigate the dementia burden effectively.

Exploring the Influence of Gut-Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics.

Recent research exploring the relationship between the gut and the brain suggests that the condition of the gut microbiota can influence cognitive health. A well-balanced gut microbiota may help reduce inflammation, which is linked to neurodegenerative conditions. Prebiotics, probiotics, and symbiotics are nutritional supplements and functional food components associated with gastrointestinal well-being. The bidirectional communication of the gut-brain axis is essential for maintaining homeostasis, with pre-, pro-, and symbiotics potentially affecting various cognitive functions such as attention, perception, and memory. Numerous studies have consistently shown that incorporating pre-, pro-, and symbiotics into a healthy diet can lead to improvements in cognitive functions and mood. Maintaining a healthy gut microbiota can support optimal cognitive function, which is crucial for disease prevention in our fast-paced, Westernized society. Our results indicate cognitive benefits in healthy older individuals with probiotic supplementation but not in healthy older individuals who have good and adequate levels of physical activity. Additionally, it appears that there are cognitive benefits in patients with mild cognitive impairment and Alzheimer's disease, while mixed results seem to arise in younger and healthier individuals. However, it is important to acknowledge that individual responses may vary, and the use of these dietary supplements should be tailored to each individual's unique health circumstances and needs.

Resilience of mental health services amidst Ebola disease outbreaks in Africa.

Introduction: Health systems including mental health (MH) systems are resilient if they protect human life and produce better health outcomes for all during disease outbreaks or epidemics like Ebola disease and their aftermaths. We explored the resilience of MH services amidst Ebola disease outbreaks in Africa; specifically, to (i) describe the pre-, during-, and post-Ebola disease outbreak MH systems in African countries that have experienced Ebola disease outbreaks, (ii) determine the prevalence of three high burden MH disorders and how those prevalences interact with Ebola disease outbreaks, and, (iii) describe the resilience of MH systems in the context of these outbreaks. Methods: This was a scoping review employing an adapted PRISMA statement. We conducted a five-step Boolean strategy with both free text and Medical Subject Headings (MeSH) to search 9 electronic databases and also searched WHO MINDbank and MH Atlas. Results: The literature search yielded 1,230 publications. Twenty-five studies were included involving 13,449 participants. By 2023, 13 African nations had encountered a total of 35 Ebola outbreak events. None of these countries had a metric recorded in MH Atlas to assess the inclusion of MH in emergency plans. The three highest-burden outbreak-associated MH disorders under the MH and Psychosocial Support (MHPSS) framework were depression, post-traumatic stress disorder (PTSD), and anxiety with prevalence ranges of 1.4-7%, 2-90%, and 1.3-88%, respectively. Furthermore, our analysis revealed a concerning lack of resilience within the MH systems, as evidenced by the absence of pre-existing metrics to gauge MH preparedness in emergency plans. Additionally, none of the studies evaluated the resilience of MH services for individuals with pre-existing needs or examined potential post-outbreak degradation in core MH services. Discussion: Our findings revealed an insufficiency of resilience, with no evaluation of services for individuals with pre-existing needs or post-outbreak degradation in core MH services. Strengthening MH resilience guided by evidence-based frameworks must be a priority to mitigate the long-term impacts of epidemics on mental well-being.