Design and rationale of a Prospective, Observational European Multicenter study on the efficacy of acute surgical decompression after traumatic Spinal Cord Injury: the SCI-POEM study

Objectives:Despite many years of research, there is currently no treatment available that results in major neurological or functional recovery after traumatic spinal cord injury (tSCI). In particular, no conclusive data related to the role of the timing of decompressive surgery, and the impact of injury severity on its benefit, have been published to date. This paper presents a protocol that was designed to examine the hypothesized association between the timing of surgical decompression and the extent of neurological recovery in tSCI patients.Study design:The SCI-POEM study is a Prospective, Observational European Multicenter comparative cohort study. This study compares acute (<12?h) versus non-acute (>12?h, <2 weeks) decompressive surgery in patients with a traumatic spinal column injury and concomitant spinal cord injury. The sample size calculation was based on a representative European patient cohort of 492 tSCI patients. During a 4-year period, 300 patients will need to be enrolled from 10 trauma centers across Europe. The primary endpoint is lower-extremity motor score as assessed according to the 'International standards for neurological classification of SCI' at 12 months after injury. Secondary endpoints include motor, sensory, imaging and functional outcomes at 3, 6 and 12 months after injury.Conclusion:In order to minimize bias and reduce the impact of confounders, special attention is paid to key methodological principles in this study protocol. A significant difference in safety and/or efficacy endpoints will provide meaningful information to clinicians, as this would confirm the hypothesis that rapid referral to and treatment in specialized centers result in important improvements in tSCI patients.     

Physicians' actions and influence, such as aggressive blood pressure control, greatly improve the health of diabetes patients

Managing diabetes and preventing its associated morbidities require active partnerships between physicians and patients. Studies to date lack the level of detail to quantify the degree to which interventions that are more controlled by physicians influence outcomes versus those that are more controlled by patients. Using the Archimedes model, we simulated a thirty-year clinical trial and compared the effects of three sets of interventions over which physicians have progressively less control: compliance with process-of-care standards, such as conducting foot and retinal exams and screening for signs of early kidney disease; control of biomarkers, such as hemoglobin A1c and blood pressure; and lifestyle modifications, such as patients' switching to healthier diets and losing weight. We found that if all US adults diagnosed with type 2 diabetes met quality targets in all of these areas, they would experience a nearly 16 percent increase in quality-adjusted life-years and a nearly 23 percent reduction in fifteen-year mortality over the thirty-year simulation period. Meeting aggressive biomarker targets yielded the most benefit. Meeting conservative biomarker targets came next, followed closely by meeting process-of-care standards. The incremental benefits of complying fully with diet and smoking cessation yielded the least benefit. Thus, through measures more readily within their control, and through collaboration with their patients, physicians have a substantial opportunity to improve outcomes. These findings can inform policy makers' rational resource allocation decisions and the design of programs to improve diabetes care.     

What happens to babies exposed to phencyclidine (PCP) in utero?

Fifty-seven infants exposed to phencyclidine (PCP) in utero were followed for the first year of life. Thirty-six (65%) of the 55 for whom birth records were available manifested symptoms of neonatal narcotic withdrawal syndrome, including 16 (52%) of those whose mothers denied opiate abuse during pregnancy. Temperament problems were noted in 47% of the babies and sleep problems in 14%. The majority of infants grew normally, but a larger than expected number started out small and remained small. Testing using the Bayley Scales of Infant Development at age one year revealed a mental development index (mean +/- SD) of 94 +/- 10 and a psychomotor development index of 98 +/- 10. Attachment behavior was abnormal in 17%. Most infants were cared for by their natural mother. Further studies are needed to determine later effects of in utero PCP exposure, as well as effects on the infants being raised by women who have used PCP. Phencyclidine toxicity needs to be considered when evaluating babies with signs of neonatal narcotic withdrawal syndrome.     

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study

Introduction

Hyperglycemia, hypoglycemia, and increased glycemic variability have each been independently associated with increased risk of mortality in critically ill patients. The role of diabetic status on modulating the relation of these three domains of glycemic control with mortality remains uncertain. The purpose of this investigation was to determine how diabetic status affects the relation of hyperglycemia, hypoglycemia, and increased glycemic variability with the risk of mortality in critically ill patients.

Methods

This is a retrospective analysis of prospectively collected data involving 44,964 patients admitted to 23 intensive care units (ICUs) from nine countries, between February 2001 and May 2012. We analyzed mean blood glucose concentration (BG), coefficient of variation (CV), and minimal BG and created multivariable models to analyze their independent association with mortality. Patients were stratified according to the diagnosis of diabetes.

Results

Among patients without diabetes, mean BG bands between 80 and 140 mg/dl were independently associated with decreased risk of mortality, and mean BG bands >140 mg/dl, with increased risk of mortality. Among patients with diabetes, mean BG from 80 to 110 mg/dl was associated with increased risk of mortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. An effect of center was noted on the relation between mean BG and mortality. Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associated with increased risk of mortality among patients with and without diabetes and increased glycemic variability, defined as CV >20%, was independently associated with increased risk of mortality only among patients without diabetes. Derangements of more than one domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes.

Conclusions

Although hyperglycemia, hypoglycemia, and increased glycemic variability is each independently associated with mortality in critically ill patients, diabetic status modulates these relations in clinically important ways. Our findings suggest that patients with diabetes may benefit from higher glucose target ranges than will those without diabetes. Additionally, hypoglycemia is independently associated with increased risk of mortality regardless of the patient''s diabetic status, and increased glycemic variability is independently associated with increased risk of mortality among patients without diabetes.See related commentary by Krinsley, http://ccforum.com/content/17/2/131See related commentary by Finfer and Billot, http://ccforum.com/content/17/2/134     

Factors associated with exposure to hepatitis B virus in injection drug users

This study was undertaken to describe factors associated with exposure to the hepatitis B virus (HBV) in treated injection drug users to better aim prevention and care in high risk subgroups. The naturalistic study was conducted in Munich, Germany, and 1,018 patients who ever shared needles admitted for opioid detoxification were included. Sociodemographic, drug and drug treatment related variables and the virological status (HCV, HIV) were included in the bivariate and multiple logistic regression analysis. Sera were tested positive for antibodies against HBc in 40.2%, against HCV in 60.9%, and against HIV in 4.7% of patients. Older age, living without partner, longer duration of IDU, positive drug treatment history, imprisonment, emergency treatment, daily alcohol consumption, type of opioid dependency, and being positive for anti-HCV or anti-HIV were significant individual factors associated with positive anti-HBc-serology. Using multiple logistic regression history of imprisonment and being positive for anti-HCV remained independently associated with positive anti-HBc-serology. HBV-infection in IDUs should alert for simultaneous HCV-infection. Contacts to the criminal justice system are to be used for HBV prevention programs, including vaccination when indicated. Prevention programs should be implemented early in or even before the begin of a drug career.     

Emerging strategies for the transdermal delivery of peptide and protein drugs

Transdermal delivery has been at the forefront of research addressing the development of non-invasive methods for the systemic administration of peptide and protein therapeutics generated by the biotechnology revolution. Numerous approaches have been suggested for overcoming the skin's formidable barrier function; whereas certain strategies simply act on the drug formulation or transiently increase the skin permeability, others are designed to bypass or even remove the outermost skin layer. This article reviews the technologies currently under investigation, ranging from those in their early-stage of development, such as laser-assisted delivery to others, where feasibility has already been demonstrated, such as microneedle systems, and finally more mature techniques that have already led to commercialisation (e.g., velocity-based technologies). The principles, mechanisms involved, potential applications, limitations and safety considerations are discussed for each approach, and the most advanced devices in each field are described.