New Dosing Strategies for an Old Antibiotic: Pharmacodynamics of Front-Loaded Regimens of Colistin at Simulated Pharmacokinetics in Patients with Kidney or Liver Disease

Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10⁸ CFU/ml) of Pseudomonas aeruginosa. The pharmacokinetics were simulated for patients with hepatic (half-life [t_1/2] of 3.2 h) or renal (t_1/2 of 14.8 h) disease. Front-loaded regimens (n = 5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve (fAUC) compared to those with traditional dosing regimens (n = 14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log₁₀ within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa. The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections.     

The Efficiency of the Sideways Stepping Test in Detecting Unilateral Vestibular Hypofunction

[Purpose] This study investigated to determine whether the Sideways Stepping Test (SST) is a useful test to detect unilateral vestibular hypofunction (UVH). [Subjects and Methods] Twenty-eight subjects including both male and females between the ages of 25 and 55 who had been diagnosed with UVH were recruited for the study. All the subjects were tested with the SST and followed by the head-shaking nystagmus (HSN) test using video electronystagmography (VENG) to confirm the presence of UVH. The results of both tests were then compared with each other to determine the correlation, sensitivity, and specificity. [Results] The results showed that the SST is strongly correlated with the gold standard HSN test using VENG and is highly sensitive and specific. [Conclusion] The present study showed that the SST is a highly valid test that can be used as an alternative method to the gold standard HSN test using VENG in detecting UVH.Key words: Unilateral vestibular hypofunction, Sideways Stepping Test, Video electronystagmography     

Laser Therapy as an Effective Method for Implant Surface Decontamination: A Histomorphometric Study in Rats

Background: To the best of the authors’ knowledge, a standard protocol for treating peri‐implantitis is not yet established. Methods: A total of 150 titanium disks with smooth or rough surfaces contaminated with microbial biofilm were implanted subcutaneously in rats after undergoing one of three treatments: 1) low‐intensity laser (LIL); 2) antimicrobial photodynamic therapy (aPDT); or 3) toluidine blue O (TBO). Sterile and contaminated disks served as negative (NC) and positive (C) control groups, respectively. After days 7, 28, and 84, tissue inflammation was evaluated microscopically by measuring the density of collagen fibers (degree of fibrosis) and concentration of polymorphonuclear neutrophils. Results: Surface texture did not affect the degree of inflammation, but the area of reactive tissue was significantly greater for rough implants (2.6 ± 3.7 × 10⁶ µm²) than for smooth ones (1.9 ± 2.6 × 10⁶ µm²; P = 0.0377). Group C presented the lowest and group NC presented the highest degree of fibrosis with significance only after day 7; these groups had the highest and lowest scores, respectively, for degree of inflammation. Group C showed the largest area of reactive tissue (9.11 ± 2.10 × 10⁶ µm²), but it was not significantly larger than group LIL (P = 0.3031) and group TBO (P = 0.1333). Group aPDT showed the smallest area (4.34 ± 1.49 × 10⁶ µm²) of reactive tissue among the treatment groups. After day 28, groups LIL, aPDT, TBO, and C resembled group NC in all the studied parameters. Conclusion: Group aPDT showed more favorable results in parameter area of reactive tissue than the other methods after day 7, but over longer time periods all methods produced outcomes equivalent to sterile implants.     

Burden of non-communicable disease: Global overview

Non-communicable diseases continue to be important public health problems in the world, being responsible for sizeable mortality and morbidity. Non-communicable diseases (NCDs) are the leading causes of death and disability worldwide. In 2005 NCDs caused an estimated 35 million deaths, 60% of all deaths globally, with 80% in low income and middle-income countries and approximately 16 million deaths in people less than 70 years of age. Total deaths from NCDs are projected to increases by a further 17% over the next 10 years. Knowing the risk factors for chronic disease means that approximately 80% premature heart disease and stroke, 80% of Type 2 diabetes and 40% of cancers are preventable. Within next 20 years, NCDs will be responsible for virtually half of the global burden of disease in the developing countries. Risk factors, such as tobacco and alcohol use, improper nutrition and sedentary behavior contribute substantially to the development of NCDs, which are sweeping the entire globe, with an increasing trend mostly in developing countries where, the transition imposes more constraints to deal with an increasing burden of over population with existing communicable diseases overwhelmed with increasing NCDs in poorly maintained sanitation and environment.By 2020, it is predicted that these diseases will be causing seven out of every 10 deaths in developing countries. A major feature of the developmental transition is the rapid urbanization and the large shifts in population from rural to urban areas. Even the rural people are increasingly adapting urbanized lifestyle. The changing pattern of lifestyle leads to the development of obesity, stroke, stress, atherosclerosis, cancer and other NCDs.Considering the future burden of NCDs and our existing health care system we should emphasize the need to prioritize the prevention and control of NCDs. Our strategies should be directed to monitor the incidence of NCDs along with their risk factors. Some NCDs have their common risk factors which should be addressed with minimum cost but maximum output. The three key components of the strategy are surveillance, health promotion and primary prevention, and management and health care.According to the WHO criteria there are three steps for screening of NCDs. Step 1: Estimation population need through assessing the current risk profile and advocate for action. Step 2: Formulate and adopt NCD policy. Step 3: Identify policy implementation steps. Management of NCDs should be to increased awareness among the public regarding the signs and symptoms of the disease and its complications.Health promotion strategies, with a strong focus on disease prevention, are needed to empower people to act both individually and collectively to prevent risky behavior, and to create economic, political and environmental conditions that prevent NCDs and their risks. Risk trends need to be monitored and intervention strategies need to be evaluated with respect to their expected outcomes. Issues such as rapid population ageing, gender and income inequality, persistent poverty and the needs of developing countries require close consideration as they influence the prevalence of NCDs – and the success of interventions.     

New tools for diagnosing spondyloarthropathy

Ankylosing spondylitis (AS) in its established and early forms accounts for more than 5% of all cases of chronic low back pain. Attention has focused recently on decreasing the time from symptom onset to the diagnosis of AS, which currently ranges from five to 10 years. An earlier diagnosis would lead to improved management, in particular thanks to the recent introduction and continuing development of biotherapies, such as TNFα antagonists, and new imaging techniques, including Doppler ultrasonography and magnetic resonance imaging have proved capable of detecting early signs of AS. Biotherapies not only improve the symptoms, but may also slow or halt the progression of the inflammatory lesions before the development of radiographic changes. Current criteria for AS (New York, Amor, and ESSG) are classification criteria that provide useful diagnostic orientation in clinical practice but have inadequate sensitivity for the diagnosis of recent-onset AS. Several groups have been working on means of improving the early diagnosis of AS. An algorithm for the early diagnosis of axial AS developed by Rudwaleit et al. needs to be confirmed by prospective studies. The Assessment of SpondyloArthritis international Society (ASAS) has just issued new diagnostic criteria for AS that performed well in a large cohort of patients with recent-onset low back pain.