Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease.

BACKGROUND & AIMS: Monitoring plasma concentrations of anti-tumor necrosis factor agents could optimize treatment of patients with Crohn's Disease (CD). In a post hoc analysis of data from a clinical trial, we compared the relationship between plasma concentrations of certolizumab pegol (CZP) and endoscopic and clinical responses and remission with CZP therapy in patients with moderate to severe ileocolonic CD. METHODS: We analyzed data from the Endoscopic Mucosal Improvement in Patients with Active CD Treated with CZP trial, from 89 adult patients with active endoscopic CD (ulceration in ≥ 2 intestinal segments and CD Endoscopic Index of Severity [CDEIS] scores of ≥ 8 points). Patients received subcutaneous CZP (400 mg) at weeks 0, 2, and 4 and then every 4 weeks until week 52. Endoscopic evaluations were performed at weeks 0, 10, and 54. Blood samples were collected to measure CZP plasma concentrations at weeks 8 and 54. CZP quartiles at weeks 8 (n = 80) and 54 (n = 45) were correlated with endoscopic response (>5-point decrease in CDEIS from baseline) and remission (CDEIS, <6) at weeks 10 and 54, respectively. RESULTS: Higher concentrations of CZP at week 8 were associated with endoscopic response (P = .0016) and remission (P = .0302) at week 10 (n = 45). At week 54, the rates of endoscopic remission correlated with plasma concentrations of CZP (P = .0206). There was a significant inverse relationship between plasma concentrations of CZP and baseline levels of C-reactive protein and body weight (P = .0014 and P = .0373, respectively). CONCLUSIONS: Endoscopic response and remission are associated with higher plasma concentrations of CZP in patients with moderate to severe ileocolonic CD. These results support the need to consider the pharmacokinetics of anti-tumor necrosis factor agents and therapeutic drug monitoring to optimize treatment. Clinicaltrials.gov Number, NCT00297648.

Texas professionals are employing a one health approach to protect the United States against biosecurity threats.

Texas is a geographically large state with large human and livestock populations, many farms, a long coastal region, and extreme fluctuations in weather. During the last 15 years, the state of Texas has frequently suffered disasters or catastrophes causing extensive morbidity and economic loss. These disasters often have complicated consequences requiring multi-faceted responses. Recently, an interdisciplinary network of professionals from multiple academic institutions has emerged to collaborate in protecting Texas and the USA using a One Health approach. These experts are training the next generation of scientists in biopreparedness; increasing understanding of pathogens that cause repetitive harm; developing new therapeutics and vaccines against them; and developing novel surveillance approaches so that emerging pathogens will be detected early and thwarted before they can cause disastrous human and economic losses. These academic One Health partnerships strengthen our ability to protect human and animal health against future catastrophes that may impact the diverse ecoregions of Texas and the world.

Pandemic diseases preparedness and response in the age of COVID-19-a symposium report.

For years, experts have warned that a global pandemic was only a matter of time. Indeed, over the past two decades, several outbreaks and pandemics, from SARS to Ebola, have tested our ability to respond to a disease threat and provided the opportunity to refine our preparedness systems. However, when a novel coronavirus with human-to-human transmissibility emerged in China in 2019, many of these systems were found lacking. From international disputes over data and resources to individual disagreements over the effectiveness of facemasks, the COVID-19 pandemic has revealed several vulnerabilities. As of early November 2020, the WHO has confirmed over 46 million cases and 1.2 million deaths worldwide. While the world will likely be reeling from the effects of COVID-19 for months, and perhaps years, to come, one key question must be asked, How can we do better next time? This report summarizes views of experts from around the world on how lessons from past pandemics have shaped our current disease preparedness and response efforts, and how the COVID-19 pandemic may offer an opportunity to reinvent public health and healthcare systems to be more robust the next time a major challenge appears.

Allocation of scarce resources after a nuclear detonation: setting the context.

The purpose of this article is to set the context for this special issue of Disaster Medicine and Public Health Preparedness on the allocation of scarce resources in an improvised nuclear device incident. A nuclear detonation occurs when a sufficient amount of fissile material is brought suddenly together to reach critical mass and cause an explosion. Although the chance of a nuclear detonation is thought to be small, the consequences are potentially catastrophic, so planning for an effective medical response is necessary, albeit complex. A substantial nuclear detonation will result in physical effects and a great number of casualties that will require an organized medical response to save lives. With this type of incident, the demand for resources to treat casualties will far exceed what is available. To meet the goal of providing medical care (including symptomatic/palliative care) with fairness as the underlying ethical principle, planning for allocation of scarce resources among all involved sectors needs to be integrated and practiced. With thoughtful and realistic planning, the medical response in the chaotic environment may be made more effective and efficient for both victims and medical responders.

Acute thyroiditis complicating parathyroidectomy.

This report describes a 59-year-old man who presented 10 days after surgery for hyperparathyroidism with pulmonary edema, mildly abnormal echocardiogram, and elevated free T4 level with suppressed thyroid-stimulating hormone level. Follow-up documented resolution of the elevated free T4 level with 24-hour thyroid scan and uptake at 60 days showing reduced uptake and normal gland anatomy. Previous case reports have been made of thyroiditis at variable time intervals after parathyroidectomy and are here reviewed. This entity represents an under appreciated potential morbidity associated with parathyroid surgical procedures.

Radiation terrorism: what society needs from the radiobiology-radiation protection and radiation oncology communities.

Society's and individuals' concerns about the adverse effects from radiation are logically amplified many times when radiological terrorism is considered. The spectrum of events include industrial sabotage, the use of an explosive or non-explosive radiological dispersal device, the placement of a radiological exposure device in a public facility and the use of an improvised nuclear device. The consequences of an event relate to the physical and medical damage of the event itself, the financial impact, and the acute and long-term medical consequences, including fear of radiation-induced cancer. The magnitude of a state-sponsored nuclear event is so great that limited detailed response planning had been done in the past, as compared to the work now ongoing. Planning is done on the basis of scenario modelling. Medical response planning includes medical triage, distribution of victims to care by experienced physicians, developing medical countermeasures to mitigate or treat radiation injury, counselling and appropriately following exposed or potentially exposed people, and helping the local community develop confidence in their own response plan. Optimal response must be based on the best available science. This requires scientists who can define, prioritise and address the gaps in knowledge with the range of expertise from basic physics to biology to translational research to systems expertise to response planning to healthcare policy to communications. Not only are there unique needs and career opportunities, but there is also the opportunity for individuals to serve their communities and country with education regarding radiation effects and by formulating scientifically based government policy.

Anthrax vaccine: immunogenicity and safety of a dose-reduction, route-change comparison study in humans.

Anthrax vaccine adsorbed (AVA), an effective countermeasure against anthrax, is administered as six subcutaneous (SQ) doses over 18 months. To optimize the vaccination schedule and route of administration, we performed a prospective pilot study comparing the use of fewer AVA doses administered intramuscularly (IM) or SQ with the current schedule and route. We enrolled 173 volunteers, randomized to seven groups, who were given AVA once IM or SQ; two doses, 2 or 4 weeks apart, IM or SQ; or six doses at 0, 2, 4 weeks and 6, 12, and 18 months (control group, licensed schedule and route). IM administration of AVA was associated with fewer injection site reactions than SQ administration. Following the first SQ dose of AVA, compared to males, females had a significantly higher rate of injection site reactions such as erythema, induration and subcutaneous nodules (P<0.001). Reaction rates decreased with a longer dose interval between the first two doses. The peak anti-PA IgG antibody response of subjects given two doses of AVA 4 weeks apart IM or SQ was comparable to that seen among subjects who received three doses of AVA at 2-week intervals. The IM route of administering this aluminum hydroxide adsorbed vaccine is safe and has comparable peak anti-PA IgG antibody levels when two doses are administered 4 weeks apart compared to the licensed initial dose schedule of three doses administered 2 weeks apart. A large pivotal study is being planned by the Centers for Disease Control and Prevention to confirm these results.

Anthrax as a biological weapon, 2002: updated recommendations for management.

OBJECTIVE: To review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population. PARTICIPANTS: The working group included 23 experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources. CONSENSUS PROCESS: The first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations. CONCLUSIONS: Specific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.