Clinical challenges of glycemic control in the intensive care unit: A narrative review

Glucose control in patient admitted to the intensive care unit has been a topic of much debate over the past 20 years. The harmful effects of uncontrolled hyperglycemia and hypoglycemia in critically ill patients is well established. Although a large clinical trial in 2001 demonstrated significant mortality and morbidity benefits with tight glucose control in this patient population, the results could not be replicated by other investigators. The “Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation” trial in 2009 established that tight glucose control was not only of no benefit, but in fact harmful due to the significant risk of hypoglycemia. The current guidelines suggest a moderate approach with the initiation of intravenous insulin therapy in critically ill patients when the blood glucose level is above 180 mg/dL. The most important factor that underpins glycemic management in intensive care unit patients is the consequent prevention of hypoglycemia. Robust glucose monitoring strategies and insulin protocols need to be implemented in order to achieve this goal.     

Impact of pharmacometrics on drug approval and labeling decisions: A survey of 42 new drug applications

The value of quantitative thinking in drug development and regulatory review is increasingly being appreciated. Modeling and simulation of data pertaining to pharmacokinetic, pharmacodynamic, and disease progression is often referred to as the pharmacometrics analyses. The objective of the current report is to assess the role of pharmacometrics at the US Food and Drug Administration (FDA) in making drug approval and labeling decisions. The New Drug Applications (NDAs) submitted between 2000 and 2004 to the Cardio-renal, Oncology, and Neuropharmacology drug products divisions were surveyed. For those NDA reviews that included a pharmacometrics consultation, the clinical pharmacology scientists ranked the impact on the regulatory decision(s). Of about a total of 244 NDAs, 42 included a pharmacometrics component. Review of NDAs involved independent, quantitative evaluation by FDA pharmacometricians, even when such analysis was not conducted by the sponsor. Pharmacometric analyses were pivotal in regulatory decision making in more than half of the 42 NDAs. Of the 14 reviews that were pivotal to approval related decisions, 5 identified the need for additional trials, whereas 6 reduced the burden of conducting additional trials. Collaboration among the FDA clinical pharmacology, medical, and statistical reviewers and effective communication with the sponsors was critical for the impact to occur. The survey and the case studies emphasize the need for early interaction between the FDA and sponsors to plan the development more efficiently by appreciating the regulatory expectations better.     

Parent perceptions important for HPV vaccine initiation among low income adolescent girls

Objective

The study aims were to assess the influence of provider recommendations on parental vaccine perceptions and identify the most potent parent vaccine perceptions for HPV vaccine series initiation considering provider recommendation strength.

Methods

We administered a questionnaire and assessed HPV vaccine claims among a stratified-random sample of parents of 9–17 year old girls enrolled in Florida's Medicaid and the Children's Health Insurance Program. Using multivariate analyses, we evaluated the associations between: (1) parent vaccine perceptions and provider recommendation strength, and (2) parent vaccine perceptions and HPV vaccine series initiation (≥1 vaccine claim or positive parental report) controlling for provider recommendation strength.

Results

The majority of the 2422 participating parents agreed that the HPV vaccine was safe (61%), would not make girls more likely to have sex (69%), and prevented cervical cancer (71%). About half (44%) reported receiving a strong provider recommendation. Compared to parents without recommendations, parents with strong recommendations had 2 to 7 times higher odds of agreeing that: vaccines are safe, the HPV vaccine is safe, not concerned about side effects, and the vaccine prevents cervical cancer. Even when considering provider recommendation strength, HPV vaccine series initiation was more likely among girls of parents who agreed rather than disagreed that the HPV vaccine was safe [odds ratio (OR) = 5.8, 95% confidence interval (CI) = 3.1, 11.1], does not cause sex (OR = 2.0, 95% CI = 1.2, 3.4), prevents cervical cancer (OR = 2.0, 95% CI = 1.0, 3.4), and prevents HPV infections (OR = 1.8, 95% CI = 1.0, 3.0).

Conclusions

Parent concerns about HPV vaccine are similar to their concerns about other vaccines. Providers should focus HPV vaccine discussions with parents on vaccine safety and illness prevention.     

Pediatric transfusion therapy: Practical considerations

Over the past decade, safety of blood has increased tremendously because of better donor screening as well as testing of the units for transmissible diseases. Component therapy has allowed more effective and economic use of blood. Whole blood is rarely used; instead, packed red cells, platelets, and fresh frozen plasma (FFP) are the most common components used. These products are further refined using irradiation and microaggregate filters and in the case of FFP, viral inactivation. Irradiation prevents transfusion-associated graft versus host disease, whereas microaggregate filters remove leukocytes, decreasing the rates of alloimmunization, febrile nonhemolytic (FNH) reactions, and cytomegalovirus (CMV) transmission. Autologous donation in older children probably provides the safest blood as far as transmissible diseases are concerned. More families request a directed donation and solicit physician help in deciding as well as making arrangements for autologous and/or directed donations. Transfusions of blood and blood components in children are often challenging and require a knowledge of physiologic changes in hemoglobin and blood volumes during different ages. The unique needs of neonates, immunocompromised patients, and patients with congenital hemolytic anemia (sickle cell, thalassemia) mandate that the pediatrician have an appropriate knowledge of transfusion volumes and choice of blood product as well as indications for transfusion.     

Local Recurrence After Transanal Endoscopic Microsurgery for Rectal Polyps and Early Cancers

Background Transanal endoscopic microsurgery (TEM) allows for local excision of rectal neoplasms with greater exposure than transanal excision and less morbidity than transabdominal approaches. This study examines the implications of the procedure with respect to predictors of recurrence. Methods We performed a retrospective analysis of 144 consecutive TEMs from 1993 to 2004. Results The study comprises 107 patients presenting for TEM with benign disease and 32 patients with cancer. Patients had a mean age of 64 ± 14 (SD) years. TEM was performed for recurrent lesions in 17% of cases. Pathologic classification of the lesions after TEM was benign adenoma in 45%, adenoma with high-grade dysplasia (HGD) in 17%, cancer in 33%, and other in 4%. Complications occurred in 10%, and local recurrence occurred in 15% of patients. Median follow-up was 44 months, with a median time to recurrence of 14 months. Positive margins did not influence lesion recurrence. Recurrence of cancers correlated with the depth of tumor invasion (P < .05). On multivariate analysis, independent predictors of recurrence were lesion size and the presence of HGD within adenomas (P < .05). Five-year neoplastic recurrence probabilities were 11% for benign adenomas, 35% for adenomas with HGD, and 20% for cancers (P = .31); invasive recurrence probabilities were 0% for benign adenomas, 15% for adenomas with HGD, and 13% for cancers (P < .05). Conclusions Close endoscopic follow-up is warranted after TEM for both benign and malignant disease, with special attention to lesions with HGD. TEM can be performed safely for early rectal cancer with careful patient selection. Presented at the Society of Surgical Oncology, 58th Annual Cancer Symposium, Atlanta, Georgia, March 3–6, 2005.     

Surgical resection of infantile hemangiomas following medical treatment with propranolol versus corticosteroids

Purpose

There has been a paradigm shift from corticosteroid to propranolol treatment for infantile hemangiomas (IHs), with surgical resection reserved for complicated or persistent IHs. The purpose of this study was to determine if propranolol treatment was associated with decreased utilization of surgical resection compared to corticosteroids.

Astroblastoma: Does histology predict biologic behavior?

Astroblastoma is a rare and controversial tumor about which little is known. We have made the diagnosis in seven patients since 1990 at Memorial Sloan-Kettering Cancer Center. Four patients had astroblastomas with anaplastic features, whereas three patients had tumors which were well-differentiated. All three patients with low grade lesions are alive and recurrence free after surgery alone (mean follow-up 29 months). All four patients with anaplastic astroblastoma were treated with surgery, radiotherapy and chemotherapy. One died of infection during induction chemotherapy. Two others died of tumor progression at 28 and 42 months. Radiographic response to chemotherapy was seen in one patient. The results of our series and other reports suggest that anaplastic histology is a prognostic factor in the setting of astroblastoma. More aggressive treatment is necessary for patients with anaplastic astroblastoma although the precise role of irradiation and chemotherapy cannot be defined at this time.