RESUMO
In May 2022, a cluster of nontravel-related cases of human mpox were reported in the United Kingdom. The outbreak has since spread worldwide infecting over 85 000 patients and causing over 100 deaths. Recent data clearly suggest that patients infected with human immunodeficiency virus (HIV) with CD4 counts less than 200 cells per mm 3 suffer significantly worse outcomes than immunocompetent patients. The available countermeasures lack robust clinical data and are deployed based on in vitro and animal studies as well as extrapolations from use against other poxviruses. In many cases, despite administration of these available treatments, initiation of antiretroviral therapy (ART), and management of suspected immune reconstitution inflammatory syndrome after initiating ART, patients die. This review summarizes available data, identifies knowledge gaps and proposes recommendations on the management of severe mpox in people living with HIV.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Mpox , Humanos , HIV , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Reino UnidoAssuntos
Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Mpox , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Terapia Antirretroviral de Alta AtividadeRESUMO
Tick-borne encephalitis (TBE) is a severe disease caused by the tick-borne encephalitis virus (TBEV). TBEV is endemic throughout Eurasia and can cause persistent neurologic deficits and death. Special Operations Forces (SOF) participating in field exercises or operations in TBE-endemic countries are at significantly increased risk of infection. Unlike Lyme disease and other tick-borne illnesses, transmission of TBEV can be immediate, and early tick removal does not reduce the risk of infection. While there are no virus-specific treatments available, the US Food and Drug Administration (FDA) recently approved a TBE vaccine that has yet to be incorporated into formal Department of Defense (DoD) recommendations. SOF medical providers should be aware of this disease entity and consider the TBE vaccine when planning exercises and operations in areas of responsibility (AORs) with TBE-endemic countries. This review serves as a refresher and update on the epidemiology, transmission, and management of TBE for the SOF provider.
Assuntos
Vírus da Encefalite Transmitidos por Carrapatos , Encefalite Transmitida por Carrapatos , Vacinas , Humanos , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/epidemiologia , Encefalite Transmitida por Carrapatos/prevenção & controleRESUMO
Prolonged Casualty Care (PCC) has become an essential component to Special Operations Forces (SOF) pre-mission training. However, it has not regularly been required in recent combat operations with the availability of medical evacuation (MEDEVAC) support. Poor weather conditions at an austere SOF outpost created an emergency unreachable by aeromedical evacuation. Herein, we report a case of an emergency bilateral above-the-knee amputation procedure performed by three Special Forces Medical Sergeants (18D(a), 18D(b), and 18D(c)) and supporting Army medics with minimal telemedicine consult and guidance.
Assuntos
Medicina Militar , Militares , Humanos , Afeganistão , Medicina Militar/educação , Militares/educação , Amputação CirúrgicaRESUMO
Crimean-Congo Hemorrhagic Fever (CCHF) is the most widespread tickborne virus causing human disease. CCHF wields a mortality rate up to 30% and was responsible for the death of a US Soldier in 2009. The virus is spread by the Hyalomma species of hard tick found across Central Europe, the Middle East, Africa, and Asia south of the 50° parallel. Infection typically consists of a 1-7-day non-specific viral prodrome, followed by onset of hemorrhagic disease on days 7-10. Severe disease may cause thrombocytopenia, transaminitis, petechial hemorrhage, hematemesis, and death typically by day 10 of illness. Education and insect control are paramount to disease prevention. Treatment is predominantly supportive care, though evidence suggests a benefit of early ribavirin administration. CCHF has caused multiple nosocomial outbreaks, and therefore consideration should be given to safe transport and evacuation of infected and exposed patients. Given the wide area of distribution, transmissibility, innocuous arthropod vectors, and high mortality rate, it is imperative that Special Operations Forces (SOF) providers be aware of CCHF and the existing countermeasures.
Assuntos
Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Humanos , Febre Hemorrágica da Crimeia/diagnóstico , Febre Hemorrágica da Crimeia/epidemiologia , Febre Hemorrágica da Crimeia/prevenção & controle , África , Oriente Médio , Surtos de DoençasRESUMO
The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has led to an unprecedented public health crisis. The collective global response has led to production of multiple safe and effective vaccines utilizing novel platforms to combat the virus that have propelled the field of vaccinology forward. Significant challenges to universal vaccine effectiveness remain, including immune evasion by SARS-CoV-2 variants, waning of immune response, inadequate knowledge of correlates of protection, and dosing in special populations. This review serves as a detailed evaluation of the development of the current SARS-CoV-2 vaccines, their effectiveness, and challenges to their deployment as a preventive tool.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Evasão da Resposta ImuneRESUMO
Purpose of Review: Invasive fungal infections are a complication of COVID-19 disease. This article reviews literature characterizing invasive fungal infections associated with COVID-19. Recent Findings: Multiple invasive fungal infections including aspergillosis, candidiasis, pneumocystosis, other non-Aspergillus molds, and endemic fungi have been reported in patients with COVID-19. Risk factors for COVID-19-associated fungal disease include underlying lung disease, diabetes, steroid or immunomodulator use, leukopenia, and malignancy. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) are the most common fungal infections described. However, there is variability in the reported incidences related to use of differing diagnostic algorithms. Summary: Fungal pathogens are important cause of infection in patients with COVID-19, and the diagnostic strategies continue to evolve. Mortality in these patients is increased, and providers should operate with a high index of suspicion. Further studies will be required to elucidate the associations and pathogenesis of these diseases and best management and prevention strategies.
RESUMO
Smallpox plagued humans for millennia until its eradication in 1980 following a successful global campaign led by the World Health Organization (WHO). It is the first known biological weapon to be used in war and has been weaponized in the past by the former Soviet Union. To date, smallpox remains a Category A Bioagent and is assessed to be a relevant threat to US military personnel. Given that the last natural case of smallpox occurred more than 40 years ago, a high level of suspicion along with a substantial understanding of the disease process are required to recognize potential future cases. While available countermeasures are limited, several new agents have recently become available for the prevention and treatment of smallpox and have been added to the strategic national stockpile. This review serves as a refresher and update for the clinical disease, to include its epidemiology and management with updated FDA-approved countermeasures.
Assuntos
Varíola , Armas Biológicas , Bioterrorismo/prevenção & controle , Humanos , Varíola/prevenção & controle , Organização Mundial da SaúdeRESUMO
BACKGROUND: Metagenomic next-generation sequencing of microbial cell-free DNA (mcfDNA) allows for non-invasive pathogen detection from plasma. However, there is little data describing the optimal role for this assay in real-world clinical decision making. METHODS: We performed a single-center retrospective cohort study of adult patients for whom a mcfDNA (Karius©) test was sent between May 2019 and February 2021. Clinical impact was arbitrated after review and discussion of each case. RESULTS: A total of 80 patients were included. The most common reason for sending the assay was unknown microbiologic diagnosis (78%), followed by avoiding invasive procedures (14%). The test had a positive impact in 34 (43%), a negative impact in 2 (3%), and uncertain or no impact in 44 (55%). A positive impact was observed in solid organ transplant recipients (SOTR, 71.4%, p = 0.003), sepsis (71.4%, p = 0.003), and those receiving antimicrobial agents for less than 7 days prior to mcfDNA testing (i.e., 61.8%, p = 0.004). Positive impact was driven primarily by de-escalation of antimicrobial therapy. CONCLUSION: Clinical impact of mcfDNA testing was highest in SOTR, patients with sepsis and patients who had been on antimicrobial therapy for less than 7 days. Positive impact was driven by de-escalation of antimicrobial therapy which may highlight a potential role for mcfDNA in the realm of stewardship.
Assuntos
Anti-Infecciosos , Ácidos Nucleicos Livres , Sepse , Adulto , Antibacterianos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Estudos Retrospectivos , Sepse/diagnósticoRESUMO
Tuberculosis (TB) causes approximately 2 million deaths annually worldwide, with 2 billion persons estimated to be actively infected with TB. While rates of active TB disease in the US military are low, military service in TB-endemic countries remains an uncommon, but important source of infection. United States Special Operations Forces (USSOF) and enablers often operate in TB-endemic countries and, as an inherent risk of their mission sets, are more likely to have high-risk exposure to TB disease. Military medical authorities have provided excellent diagnostic guidance; the Centers for Disease Control and Prevention (CDC) recently updated preferred regimens for the treatment of latent TB infection (LTBI). This review serves as a refresher and update to the management of LTBI in USSOF to optimize medical readiness through targeted testing and short treatment regimens.
Assuntos
Tuberculose Latente , Militares , Tuberculose , Centers for Disease Control and Prevention, U.S. , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Invasive aspergillosis (IA) is an important opportunistic infection among patients with liver disease and liver transplants. Diagnosis of IA may be challenging, especially among patients with central nervous system infection. Herein, we demonstrate the utility of next-generation sequencing of microbial cell-free DNA in the diagnosis of fungal brain abscess in a liver transplant recipient.
Assuntos
Aspergilose , Transplante de Fígado , Neuroaspergilose , Aspergilose/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Transplante de Fígado/efeitos adversos , Neuroaspergilose/diagnóstico , Análise de Sequência de DNARESUMO
BACKGROUND: Performing systematic reviews is a time-consuming and resource-intensive process. OBJECTIVE: We investigated whether a machine learning system could perform systematic reviews more efficiently. METHODS: All systematic reviews and meta-analyses of interventional randomized controlled trials cited in recent clinical guidelines from the American Diabetes Association, American College of Cardiology, American Heart Association (2 guidelines), and American Stroke Association were assessed. After reproducing the primary screening data set according to the published search strategy of each, we extracted correct articles (those actually reviewed) and incorrect articles (those not reviewed) from the data set. These 2 sets of articles were used to train a neural network-based artificial intelligence engine (Concept Encoder, Fronteo Inc). The primary endpoint was work saved over sampling at 95% recall (WSS@95%). RESULTS: Among 145 candidate reviews of randomized controlled trials, 8 reviews fulfilled the inclusion criteria. For these 8 reviews, the machine learning system significantly reduced the literature screening workload by at least 6-fold versus that of manual screening based on WSS@95%. When machine learning was initiated using 2 correct articles that were randomly selected by a researcher, a 10-fold reduction in workload was achieved versus that of manual screening based on the WSS@95% value, with high sensitivity for eligible studies. The area under the receiver operating characteristic curve increased dramatically every time the algorithm learned a correct article. CONCLUSIONS: Concept Encoder achieved a 10-fold reduction of the screening workload for systematic review after learning from 2 randomly selected studies on the target topic. However, few meta-analyses of randomized controlled trials were included. Concept Encoder could facilitate the acquisition of evidence for clinical guidelines.
Assuntos
Aprendizado de Máquina/normas , Redes Neurais de Computação , Carga de Trabalho/normas , Algoritmos , Guias como Assunto , Humanos , Programas de RastreamentoRESUMO
The US Joint Trauma System (JTS) recommends stored whole blood (SWB) as the preferred product for prehospital resuscitation of battlefield casualties in both their Tactical Combat Casualty Care (TCCC) guidelines and their clinical practice guidelines (CPGs). Clinical data from nearly 2 decades of war during Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) suggest that whole blood (WB) is safe, effective, and far superior to crystalloid and colloid resuscitation fluids. The JTS CPG for whole blood transfusion reflects the most recent clinical evidence but poses unique challenges for execution by Special Operations Forces (SOF) operating in austere environments. Given the limited shelf-life of 35 days, WB requires a constant steady pool of donors. Additionally, the cold-chain requirement for storage poses challenges for SOF on long missions without access to blood refrigerators. SOF operating in less-developed theaters face additional logistical challenges. To mitigate the challenges of WB delivery, US SOF have implemented various protocols to ensure optimal donor pool, awareness/education among medics and specialized equipment for tactical methods of blood-carry and delivery. In general, steps taken include the following: (1) Prior to deployment, soldiers are screened for blood type and titers in order to establish a large donor pool. Support soldiers have been found to be particularly beneficial donors as they typically are in closer proximity to the blood support detachment. (2) In units that operate in smaller teams, such as ODAs, medics are outfitted with "blood kits" to carry blood on missions for point of injury transfusion. In units with larger teams, LTOWB donors are identified on missions and deliver fresh WB in the event of casualties. (3) Medics receive a WB transfusion refresher tabletop exercise and review after action reviews from previous rotations. Additionally, prehospital WB delivery is a required component of scenario-based premission training. The expectation is that medics will administer WB on missions when tactically feasible. Using the prolonged field care framework (ruck, truck, house) as a template, medics now use different methods to store and transport the SWB depending on phase. Medic "truck" and "house" kits include the Dometic CFX™ powered coolers that run on AC, DC, or solar power and allow for constant temperature monitoring. When on foot, medics have been outfitted with tactical blood coolers including the Pelican Biomedical Medic 4™ or Combat Medical Blood Box™ along with a Belmont Buddy-Lite™ intravenous (IV) infusion warmer and IV administration kit with standard micron filter. Presently, SOF medics have the donor support, logistical framework, training, and equipment to deliver WB at the point of injury. However, widespread implementation will require expanded distribution and standardization of "blood kits." Additionally, SOF medical planners must put greater emphasis on education and the importance of WB over crystalloids or colloids-as many medics continue to carry only these products out of convenience. As SOF strive to establish tactics, techniques, and procedures (TTPs) and streamline prehospital WB delivery, we must constantly reassess and refine our procedures, incorporate the latest evidence and technology, and adapt to an evolving battlefield.
Assuntos
Transfusão de Sangue , Serviços Médicos de Emergência/tendências , Medicina Militar/tendências , Ressuscitação/métodos , Lesões Relacionadas à Guerra/terapia , Campanha Afegã de 2001- , Previsões , Humanos , Guerra do Iraque 2003-2011 , Guias de Prática Clínica como AssuntoRESUMO
Q fever is a significant infectious disease threat to US military personnel deployed in the Middle East. Its environmental stability, aerosol transmission, and animal reservoir make it a considerable risk for deployed troops due to its potential for weaponization and risk of natural infection. It presents as a flu-like illness that responds promptly to antimicrobial therapy. Q fever should be suspected in patients presenting with a compatible febrile illness in an endemic area and especially if the individual has been exposed to livestock. Diagnosis is confirmed with serologic blood tests, but empiric therapy should be initiated when Q fever is considered. If left untreated, patients with acute Q fever can develop severe complications as well as chronic disease manifesting several months after the initial infection.
Assuntos
Militares , Febre Q/diagnóstico , Febre Q/tratamento farmacológico , Doença Aguda , Antibacterianos/uso terapêutico , Doença Crônica , Doxiciclina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Oriente MédioRESUMO
Middle East respiratory syndrome (MERS) emerged in the Arabian Peninsula in 2012, and subsequently spread to other countries in Europe and Asia, and to the United States. As of August 2015, the disease has infected 1,400 patients, of whom 500 have died, yielding a 36% mortality rate. The exact mode of transmission is unknown and there are no proven treatments. While the overall case rate for MERS has been low, its presence in countries that house US troops, unknown mode of transmission, and high mortality rate make it a significant health concern among US military personnel.
Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Militares , Infecções por Coronavirus/epidemiologia , Humanos , Isolamento de Pacientes , Estados UnidosRESUMO
PURPOSE: Abiraterone acetate (AA) was recently approved for castration-resistant prostate cancer in Japan. Two phase 1 studies were conducted to assess the pharmacokinetics of abiraterone after single-dose administration in Japanese healthy men and to evaluate the effects of food timing on abiraterone pharmacokinetics after single-dose administration of AA in Japanese and Caucasian healthy men. METHODS: In the dose-proportionality study, subjects (n = 30 Japanese) were randomly assigned to receive single doses of 250, 500, and 1,000 mg AA, and in the food-timing study, subjects (n = 22 Japanese and n = 23 Caucasian) randomly received single doses of 1,000 mg AA under fasted (overnight) and three different modified fasting conditions. RESULTS: Mean C(max) and AUC(∞) for abiraterone increased dose-dependently in Japanese healthy men; however, 90 % confidential interval (CI) was outside the predefined dose-proportionality criteria. Based on geometric mean ratios and 90 % CIs (versus overnight fasting condition), abiraterone exposure (AUC) increased significantly with dosing 1 h premeal, 2 h postmeal, or in between two meals 4 h apart by 57 %, 595 %, and 649 %, respectively. CONCLUSION: No clinically meaningful difference was observed in the pharmacokinetics of abiraterone between Caucasian and Japanese subjects.
Assuntos
Androstenos/farmacocinética , Antineoplásicos Hormonais/farmacocinética , Inibidores das Enzimas do Citocromo P-450/farmacocinética , Interações Alimento-Droga , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Acetato de Abiraterona , Adulto , Androstenos/administração & dosagem , Androstenos/efeitos adversos , Androstenos/sangue , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/sangue , Asiático , Estudos Cross-Over , Inibidores das Enzimas do Citocromo P-450/administração & dosagem , Inibidores das Enzimas do Citocromo P-450/efeitos adversos , Inibidores das Enzimas do Citocromo P-450/sangue , Relação Dose-Resposta a Droga , Interações Alimento-Droga/etnologia , Meia-Vida , Humanos , Japão/etnologia , Masculino , Refeições , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/etnologia , Comprimidos , Estados Unidos , População Branca , Adulto JovemRESUMO
A 23-year-old, previously healthy, deployed U.S. soldier presented with bilateral temporal lobe seizures recalcitrant to multiple antiepileptic drugs and anti-seizure anaesthetic agents. He received methylprednisolone, intravenous immunoglobulins, plasma exchange, and rituximab for presumed autoimmune encephalitis before achieving seizure freedom. Six weeks after presentation, the aetiology of his refractory seizures was found to be due to autoantibodies targeting the anti-GABA(B)-receptor. This case is noteworthy for being the first reported case of anti-GABA(B)-receptor limbic encephalitis presenting with new-onset refractory status epilepticus (NORSE), a clinical syndrome that often carries a grave prognosis and in which a treatable aetiology is often never discovered. Our case also supports testing for GABA-receptor autoantibodies and the upfront use of multi-modal immunotherapy in patients presenting with limbic encephalitis and new refractory seizures.
Assuntos
Autoanticorpos/sangue , Encefalite Límbica/imunologia , Receptores de GABA-B/imunologia , Estado Epiléptico/imunologia , Eletroencefalografia , Humanos , Encefalite Límbica/diagnóstico , Encefalite Límbica/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Militares , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamento farmacológico , Adulto JovemRESUMO
OBJECTIVE: Sirukumab (CNTO 136) is a human mAb with high affinity and specificity for binding to interleukin-6. This Phase 1 study evaluated the pharmacokinetics, immunogenicity, safety, and tolerability of sirukumab following a single subcutaneous (s.c.) administration in healthy male Japanese and Caucasian subjects. METHODS: Japanese and Caucasian subjects were randomized to placebo or 25, 50, or 100 mg sirukumab. Blood samples were collected to measure serum sirukumab concentration and antibodies to sirukumab. Noncompartmental analysis and population pharmacokinetic modeling were conducted to characterize sirukumab pharmacokinetics. Adverse events were monitored at each visit. RESULTS: 25 Japanese and 24 Caucasian subjects received sirukumab and were included in the pharmacokinetic evaluation. Mean Cmax and AUC0-∞of sirukumab increased in an approximately dose-proportional manner in both Japanese and Caucasian subjects. Median tmax was 3 -5 days after s.c. administration of sirukumab. Mean t1/2 was 15 -16 days in Japanese and 15 -18 days in Caucasian subjects. A one-compartment population pharmacokinetic model adequately described sirukumab pharmacokinetics following s.c. administration. The estimated population means for CL/F, V/F, and Ka were 0.54 ±0.03 l/day, 12.2 ±0.55 l, and 0.77 ±0.07 day-1, respectively. Race was not a significant covariate on CL/F or V/F. No subject was positive for antibodies to sirukumab. Adverse events were generally mild and did not appear to be dose-related or lead to study discontinuation. CONCLUSIONS: Sirukumab pharmacokinetics following subcutaneous administration was linear at doses ranging 25 -100 mg and was comparable between Japanese and Caucasian subjects. A single subcutaneous administration of 25, 50, or 100 mg sirukumab appeared to be well tolerated by both Japanese and Caucasian healthy male subjects.