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The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Methods
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Results
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
Conclusions
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
Biological warfare has been a threat to humanity since ancient times and crude attempts at bioterrorism have been a growing concern for several decades. In June of 1999, U.S. public health experts met at CDC headquarters and used this rationale to develop a list of critical biological agents for health preparedness. Category A agents are those that, if released effectively, would be expected to have a high overall public health impact. Category B agents present a somewhat lesser requirement for preparedness, whereas category C agents require vigilance to guard against their future development as threat agents, but can be adequately managed within the framework of the existing public health infrastructure. To understand current biological warfare medical countermeasures research strategy and progress within the United States, it is useful to review weapons of mass destruction (WMD) medical countermeasure research programs led by Department of Defense, and the Department of Homeland Security.
This study intended to create symptom-based triage algorithms for the initial encounter with terror-attack victims. The goals of the triage algorithms include: (1) early recognition; (2) avoiding contamination; (3) early use of antidotes; (4) appropriate handling of unstable, contaminated victims; and (5) provisions of force protection. The algorithms also address industrial accidents and emerging infections, which have similar clinical presentations and risks for contamination as weapons of mass destruction (WMD).
Methods:
The algorithms were developed using references from military and civilian sources. They were tested and adjusted using a series of theoretical patients from a CD-ROM chemical, biological, radiological/nuclear, and explosive victim simulator. Then, the algorithms were placed into a card format and sent to experts in relevant fields for academic review.
Results:
Six inter-connected algorithms were created, described, and presented in figure form. The “attack” algorithm, for example, begins by differentiating between overt and covert attack victims (A covert attack is defined by epidemiological criteria adapted from the Centers for Disease Control and Prevention (CDC) recommendations). The attack algorithm then categorizes patients either as stable or unstable. Unstable patients flow to the “Dirty Resuscitation” algorithm, whereas, stable patients flow to the “Chemical Agent” and “Biological Agent” algorithms. The two remaining algorithms include the “Suicide Bomb/Blast/Explosion” and the “Radiation Dispersal Device” algorithms, which are inter-connected through the overt pathway in the “Attack” algorithm.
Conclusion:
A civilian, symptom-based, algorithmic approach to the initial encounter with victims of terrorist attacks, industrial accidents, or emerging infections was created. Future studies will address the usability of the algorithms with theoretical cases and utility in prospective, announced and unannounced, field drills. Additionally, future studies will assess the effectiveness of teaching modalities used to reinforce the algorithmic approach.