Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

The influence of reverse-thread screw femoral fixation on laxity measurements after anterior cruciate ligament reconstruction with hamstring tendon

In arthroscopically assisted anterior cruciate ligament reconstruction using hamstring tendon graft, the graft rotates slightly as the femoral screw is inserted. Its final position tends to be in the anterior half of the tunnel in right knees, resulting in clinical laxity. To perform identical procedures on left and right knees, a reverse-thread screw was designed for femoral fixation in right knees. We prospectively studied 80 patients undergoing right-knee anterior cruciate ligament reconstruction with hamstring tendon autograft. Thirty-six patients underwent reconstruction with a standard screw and 44 underwent reconstruction with a reverse-thread screw. The same technique, performed by the same surgeon, was used on all patients. At 12 months' follow-up, the average side-to-side differences on arthrometry testing were 2.00 mm for the standard screw group and 0.95 mm for the reverse-thread screw group using a manual maximum test, and 1.66 mm and 1.00 mm, respectively, using the 20-pound test. Both differences were statistically significant. Of the standard group, 23% had a manual maximum difference of 3 mm or more, compared with 8% of the reverse-thread group. A significant difference was found between these two groups for Lachman test (77% with grade 0 for the standard group compared with 92% for the reverse group) but pivot shift and Lysholm knee score were not significantly different. The use of a reverse-thread screw for femoral fixation in right-knee anterior cruciate ligament reconstructions in men significantly decreased laxity at 12 months after surgery compared with standard screw fixation.     

Strategic,feasibility, economic,and cultural aspects of phase 0 approaches: Is it time to change the drug development process in order to increase productivity?

Research conducted over the past 2 decades has enhanced the validity and expanded the applications of microdosing and other phase 0 approaches in drug development. Phase 0 approaches can accelerate drug development timelines and reduce attrition in clinical development by increasing the quality of candidates entering clinical development and by reducing the time to “go‐no‐go” decisions. This can be done by adding clinical trial data (both healthy volunteers and patients) to preclinical candidate selection, and by applying methodological and operational advantages that phase 0 have over traditional approaches. The main feature of phase 0 approaches is the limited, subtherapeutic exposure to the test article. This means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first‐in‐human (FIH) testing. Whereas many operational aspects of phase 0 approaches are similar to those of other early phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. Here, we provide a guidance to these operational aspects and include case studies to highlight their potential impact in a range of clinical development scenarios.     

Traumatic lumbar hernia: report of cases and comprehensive review of the literature

BACKGROUND: Acute lumbar hernia secondary to blunt trauma is an uncommon injury of the abdominal wall and, when encountered, is a difficult challenge for the trauma surgeon. METHODS: Three cases of lumbar hernia secondary to blunt trauma are described and a review of the literature was conducted for other such cases. Clinical, anatomic, and demographic data were extracted from these reports and analyzed. RESULTS: Sixty-three cases of lumbar hernia secondary to blunt trauma were found in the English literature and three cases are described here. Hernias occurred most commonly in the inferior lumbar triangle (70%) and were most frequently a result of a motor vehicle collision (71%). Physical examination findings were variable and reported in only a minority of cases (palpable hernia, 33%; flank hematoma, 27%) and associated intra-abdominal injuries were common (61%). Most traumatic lumbar hernias were diagnosed immediately, and computed tomography was 98% sensitive for diagnosis. Fifty-eight percent of patients were managed initially with exploratory laparotomy. Timing of hernia repair was variable. CONCLUSION: Traumatic lumbar hernias are associated with a high incidence of intra-abdominal injury and should be considered in all cases of severe blunt abdominal trauma. Computed tomography should be implemented when the diagnosis is suspected in a hemodynamically stable patient. Repair should be performed by mesh patching techniques at a time based on clinical correlation.     

Innovation in growing rod technique: a study of safety and efficacy of a magnetically controlled growing rod in a porcine model

STUDY DESIGN.: Prospective in vivo randomized study. OBJECTIVE.: To evaluate the safety and efficacy of a distraction-based magnetically controlled growing rod (MCGR) in a porcine model. SUMMARY OF BACKGROUND DATA.: A high number of complications related to frequent surgical rod lengthenings has been a generally accepted outcome in growing rod surgery for early-onset scoliosis. A potentially safer technique is a system that does not require repetitive surgery. METHODS.: Seven-month-old pigs were randomly assigned to an experiment group (EG; n = 6) and a sham group (SG; n = 3). One animal in the EG became paralyzed because of a misplaced pedicle screw and was killed per the study protocol. Therefore, a total of 8 animals completed the study. The EG underwent weekly spine distraction using the MCGR. Spinal height was assessed by vertebral unit height measurements on weekly lateral radiographs. RESULTS.: A total of 49 mm of distraction across the unfused vertebral levels was planned during a 7-week period (7 mm per wk). Radiographical analysis of the MCGR device revealed an average distraction of 39 mm (range, 32-46 mm), resulting in achievement of 80% of predicted spinal height. Prior to removal of implants, spinal height for the EG was similar to the SG. However, accelerated increase in vertebral unit height was noted in the EG during the 3-week period after implant removal, which resulted in significantly greater overall spinal height in the EG (32.2% vs. 11.7%, P ≤ 0.05). No MCGR-related complications occurred. CONCLUSION.: The MCGR provided 80% of predicted spinal height by noninvasive remote distraction in this animal model. The accelerated increase in spinal height of the experimental animals after implant removal was an unexpected finding which requires additional research to better understand the effect of distraction on spinal growth. This study establishes a foundation for future research in an attempt to use a less invasive technique in distraction-based correction of early-onset scoliosis.