Issues in the design of clinical trials for safety in HIV-infected children

The use of newly approved drugs for human immunodeficiency virus (HIV)-infected adults is limited in children until child-specific pharmacokinetic and safety data can be submitted to the Food and Drug Administration (FDA) to fulfill labeling requirements. Design of a clinical trial to assess drug safety in children requires a different set of issues from standard Phase II and III efficacy trials in adults. For example, Phase II trials in adults are done to collect preliminary efficacy information. In children, efficacy of the drug is assumed and only safety needs to be shown. As a result, control groups may not be required and it may not be necessary to show superiority of the new drug over a control. This paper describes these issues in some detail and gives examples of designs appropriate in different scenarios.     

The cylindrical titanium mesh cage for treatment of a long bone segmental defect: description of a new technique and report of two cases

This report describes a new technique for treatment of a segmental defect in long bones that uses a cylindrical titanium mesh cage, in combination with cancellous bone allograft and demineralized bone matrix putty (Grafton), stabilized with a statically locked intramedullary nail. Two clinical cases of tibia defects treated with this technique are presented. At the one-year follow-up, radiographically both cases demonstrated excellent limb alignment, stability, and bony healing. Immediate full weight-bearing was initiated in each case, and early limb functional recovery was achieved. Preliminary data suggest that this technique may be a reasonable alternative to currently used methods for management of select long bone segmental defects.     

Incidence of respiratory disorders in neonates born between 34 and 36 weeks of gestation following exposure to antenatal corticosteroids between 24 and 34 weeks of gestation

We studied the effect of antenatal corticosteroids on the incidence of respiratory disorders in singleton neonates born between 34 and 36 weeks of gestation. Retrospective analysis was conducted of the incidence of respiratory distress syndrome (RDS) and other respiratory disorders (need for mechanical ventilation, continuous positive airway pressure, and prolonged oxygen therapy) among singleton neonates delivered between 34 and 36 weeks of gestation who were exposed to antenatal corticosteroids, compared with neonates who were not exposed. Statistical analyses included two-tailed T tests, two-way analysis of variance for continuous data, and chi-square analysis for ratios. A probability of 0.05 was considered significant. Between January 1, 2000, and December 31, 2004, 1078 neonates were born between 34 and 36 weeks of gestation. Information regarding antenatal corticosteroids was available in 1044: 574 neonates (53.2%) were exposed to antenatal corticosteroids and 470 (43.6%) were not. One thousand and eighteen neonates were admitted to the neonatal intensive care unit. Respiratory disorders were diagnosed in 140 of those exposed to antenatal steroids (24.4%) and in 382 of the nonexposed (81.3%) ( P < 0.0001). Two hundred and ten neonates (20.6%) developed RDS: Of those, 43 were exposed to antenatal corticosteroids and 167 were not (incidence of RDS was 7.5% and 35.5%, respectively; P = 0.0001). The beneficial effects of corticosteroids were similar in both genders. It appears that the exposure of singleton pregnancies to antenatal corticosteroids between 24 and 34 weeks of gestation is associated with a significantly lower incidence of respiratory disorders among neonates born at 34 to 36 weeks of gestation. Further studies are needed to determine whether administering antenatal steroids to women experiencing preterm labor after 34 weeks of gestation would be associated with a similar beneficial effect.     

Investigation of COVID-19 Outbreak among Wildland Firefighters during Wildfire Response,Colorado, USA, 2020

A COVID-19 outbreak occurred among Cameron Peak Fire responders in Colorado, USA, during August 2020–January 2021. The Cameron Peak Fire was the largest recorded wildfire in Colorado history, lasting August–December 2020. At least 6,123 responders were involved, including 1,260 firefighters in 63 crews who mobilized to the fire camps. A total of 79 COVID-19 cases were identified among responders, and 273 close contacts were quarantined. State and local public health investigated the outbreak and coordinated with wildfire management teams to prevent disease spread. We performed whole-genome sequencing and applied social network analysis to visualize clusters and transmission dynamics. Phylogenetic analysis identified 8 lineages among sequenced specimens, implying multiple introductions. Social network analysis identified spread between and within crews. Strategies such as implementing symptom screening and testing of arriving responders, educating responders about overlapping symptoms of smoke inhalation and COVID-19, improving physical distancing of crews, and encouraging vaccinations are recommended.     

Is Isolated Systolic Hypertension Worse Than Combined Systolic/Diastolic Hypertension?

J Clin Hypertens (Greenwich). 2012;14:808–809. ©2012 Wiley Periodicals, Inc. New developments in cardiovascular translational sciences have significantly advanced our understanding of the endovascular biology of blood pressure. Reductions in vascular elasticity and vessel compliance of conduit arteries are key components of both ISH and SDH. Vascular changes from the matrix metalloproteinase family of enzymes are involved in arterial wall remodeling and vascular stiffness. This new translational information helps further our understanding of both ISH and SDH.