Relation between prepublication release of clinical trial results and the practice of carotid endarterectomy

Context  Little is known about how clinical practice is affected by disseminating results of clinical trials prior to publication in peer-reviewed journals. Objective  To determine whether prepublication release of carotid endarterectomy (CEA) trial results via National Institutes of Health Clinical Alerts was associated with prompt changes in patient care that were consistent with the new medical evidence. Design, Setting, and Patients  Longitudinal data series analysis using acute care hospital discharge data from the Healthcare Cost and Utilization Project for patients who had CEA performed in acute care hospitals in 7 states (New York, California, Pennsylvania, Florida, Colorado, Illinois, and Wisconsin). The trials were the North American Symptomatic Carotid Endarterectomy Trial (NASCET clinical alert released February 1991) and the Asymptomatic Carotid Atherosclerosis Study (ACAS clinical alert released September 1994). Main Outcome Measure  Carotid endarterectomy rate during each month from 1989 (2 years before the NASCET clinical alert) to 1996 (2 years after the ACAS clinical alert), adjusted for age and sex. Because both trials were limited to patients 80 years or younger in hospitals with low mortality, we also stratified CEA rates by patient age and hospital mortality rate. Results  From 1989 through 1996, 272,849 CEAs were performed in the acute care hospitals in these 7 states, with the annual number increasing from 22,300 to 51,495. After the NASCET clinical alert, the adjusted CEA rate increased 3.4% per month (95% confidence interval [CI], 1.6%-5.3%) during the following 6 months and then increased 0.5% per month (95% CI, 0.2%-0.8%; P<.04) after journal publication of the NASCET study. After the ACAS clinical alert, the CEA rate increased 7.3% per month (95% CI, 6.0%-8.5%) during the following 7 months and then decreased by 0.44% per month (95% CI, -0.86% to -0.0002%; P<.04) after journal publication of the ACAS study. After the ACAS clinical alert, the CEA rate increased more in patients aged 80 years or older than in younger patients; whereas, after journal publication of ACAS, the CEA rate decreased more rapidly in the older population. The overall proportion of CEAs performed in low-mortality hospitals did not change substantially after release of the clinical alerts or after journal publication. Conclusion  In this study, prepublication dissemination of CEA trial results with clinical alerts was associated with prompt and substantial changes in medical practice, but the observed changes suggest that the results were extrapolated to patients and settings not directly supported by the trials.      

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.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

Rhythmic midbrain-evoked vocalization is inhibited by vasoactive intestinal polypeptide in the teleost Porichthys notatus

Vasoactive intestinal polypeptide (VIP) is distributed in vocal midbrain areas of multiple vertebrate taxa, suggesting that VIP may modulate midbrain-evoked vocalization. To test this hypothesis, neurophysiological experiments were conducted in the teleost Porichthys notatus which generates vocalizations in mating and agonistic contexts. Electrical stimulation of the paralemniscal midbrain and local delivery of VIP were conducted in conjunction with occipital nerve recordings that reflect the patterned output of hindbrain vocal circuitry. Consistent with our hypothesis, VIP significantly reduced the duration and number of rhythmic vocal-motor bursts obtained in a dose-dependent manner; vocalization latency was concomitantly increased. These results provide the first evidence for VIP modulation of midbrain vocal function.     

Detecting changes in functional ability in women with premenstrual syndrome

There has been a lack of objective assessment of the disruptive effect that the symptomatology of premenstrual syndrome has on the functional performance of affected women. This study assessed the functional performance of women with premenstrual syndrome at four phases of the menstrual cycle. Twelve women with premenstrual syndrome and nine asymptomatic women were tested on four functional instruments at the menstrual, early follicular, early luteal, and late luteal phases. Two tests of a paper-and-pencil type measured perceptual parameters, and two tests involving manipulation of objects measured manual dexterity. Mean performance on the Crawford Small Parts Dexterity Test--Part II, which tests fine motor function, was better at the late luteal testing, compared to the early follicular testing, in asymptomatic women but was worse in the women with premenstrual syndrome. This difference was statistically significant (p = 0.015). No significant differences between groups in performance changes were observed for the other functional tests. The Crawford Small Parts Dexterity Test-Part II is an objective measure that is potentially valuable in therapeutic trials involving patients with premenstrual syndrome.     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

Prophylactic furosemide in severe respiratory distress syndrome: blinded prospective study

To further characterize the place for furosemide in the treatment of newborn infants with respiratory distress syndrome requiring mechanical ventilation, we conducted a blinded, prospective study comparing early prophylactic use (1 mg/kg every 12 hours for four doses beginning at 24 hours of age) with prn use of this drug. Prophylactic administration of furosemide produced no beneficial effect on any measure of pulmonary function compared with use of this drug as needed (prn). However, patients receiving the prophylactic furosemide regimen were found to have more rapid postnatal weight loss, higher pulse rate, and greater sympathomimetic drug requirement during the period of diuretic administration. Patients in the prophylactic group did not demonstrate the moderate expansion in plasma volume between 48 and 96 hours of age seen in the control group. These data suggest that the prophylactic regimen produced an undesirable degree of volume depletion. Further studies should be conducted to develop objective criteria for the selection of the subgroup of patients with respiratory distress syndrome who may benefit from furosemide.     

Proinflammatory cytokine-receptor interaction model improves the predictability of cerebral white matter injury in preterm infants

Proinflammatory cytokines have been variably linked to development of cerebral white matter injury (WMI) in preterm infants. Because soluble receptors tightly control cytokine bioactivity, we modeled cytokine-receptor interaction as a predictor of WMI. Plasma from 100 preterm infants was assayed for cytokines (tumor necrosis factor alpha, interleukin (IL-1beta, IL-6) and their soluble receptors (sTNF-RI), sTNF-RII, sIL-1RA, and sIL-6R). Cranial ultrasound (US) results were correlated with cytokine and receptor concentrations individually and with cytokine-receptor interaction models (PROC LOGISTIC; SAS Software). Receiver operating characteristic curves were constructed to determine the predictability of WMI. Fifty-two infants with normal US exams were compared with 21 infants with evidence of WMI. There was no association between individual cytokine or receptor concentrations and the development of WMI. However, modeling cytokines with their soluble receptors significantly improved the predictability of WMI. We concluded that consideration of cytokine-receptor interaction may be more important than individual cytokine concentrations alone in determining the role of inflammation in the pathogenesis of WMI in preterm infants.     

Diagnostic test characteristics of placental weight in the prediction of small-for-gestational-age neonates

OBJECTIVE: To assess the diagnostic test characteristics of placental weight as a clinical predictor of small-for-gestational-age (SGA) neonates. STUDY DESIGN: Placentas were weighed at 45,846 deliveries. Predictive values and likelihood ratios (LRs) were calculated assessing placental weight (lowest tertile vs. top 2 or mid/high tertiles) as a predictor of SGA both overall and by maternal age, gestational age, maternal weight, reported early pregnancy smoking, race, neonatal sex and parity. RESULTS: Although the positive predictive value (PPV) of low placental weight was poor (0.19), the negative predictive value (NPV) was high (0.97). Both NPV and LR- were powerfully predictive in women at earlier gestational ages. At gestational ages <32 weeks, LR-was 0.11, showing that among women with mid/high placental weight, the proportion with SGA (false negative) was about 1/10 that without SGA (true negative). CONCLUSION: Placental weight in the mid or upper tertile has strong NPV and LR- for delivery of an SGA neonate. Further study of the value of placental size in prediction of SGA is warranted.