Effect of dose on response to adrenocorticotropin in extremely low birth weight infants

CONTEXT: Various cosyntropin doses are used to test adrenal function in premature infants, without consensus on appropriate dose or adequate response. OBJECTIVE: The objective of this study was to test the cortisol response of extremely low birth weight infants to different cosyntropin doses and evaluate whether these doses differentiate between groups of infants with clinical conditions previously associated with differential response to cosyntropin. DESIGN: The design was a prospective, nested study conducted within a randomized clinical trial of low-dose hydrocortisone from November 1, 2001, to April 30, 2003. SETTING: The setting was nine newborn intensive care units. PATIENTS: The patients included infants with 500-999 g birth weight. INTERVENTION: The drug used was cosyntropin, at 1.0 or 0.1 microg/kg, given between 18 and 28 d of birth. MAIN OUTCOME MEASURE: We measured the cortisol response to cosyntropin. RESULTS: Two hundred seventy-six infants were tested. Previous hydrocortisone treatment did not suppress basal or stimulated cortisol values. Cosyntropin, at 1.0 vs. 0.1 microg/kg, yielded higher cortisol values (P < 0.001) and fewer negative responses (2 vs. 21%). The higher dose, but not the lower dose, showed different responses for girls vs. boys (P = 0.02), infants receiving enteral nutrition vs. not (P < 0.001), infants exposed to chorioamnionitis vs. not (P = 0.04), and those receiving mechanical ventilation vs. not (P = 0.02), as well as a positive correlation with fetal growth (P = 0.03). A response curve for the 1.0-microg/kg dose for infants receiving enteral nutrition (proxy for clinically well infants) showed a 10th percentile of 16.96 microg/dl. Infants with responses less than the 10th percentile had more bronchopulmonary dysplasia and longer length of stay. CONCLUSIONS: A cosyntropin dose of 0.1 microg/kg did not differentiate between groups of infants with clinical conditions that affect response. We recommend 1.0 microg/kg cosyntropin to test adrenal function in these infants.     

A novel enteropathy with partial villous atrophy, microscopic colitis, and pemphigoid change

Microscopic colitis associated with gluten-resistant partial villous atrophy was documented in a 21-year-old woman with chronic nonbloody diarrhea. Electron microscopic examination of the colonic and duodenal biopsies showed focal separations of basal lamina from cryptal epithelial cells forming subepithelial blebs in which were mast cells and fibroblasts. These morphologic features have not been previously described in any inflammatory bowel disease and are reminiscent of bullous pemphigoid of the skin. The findings suggest that not all cases of microscopic colitis lie within the spectrum of collagenous colitis.     

A comparison by race/ethnicity of narcotic addict crime rates in Baltimore, New York, and Philadelphia

In an effort to provide timely information concerning the criminal activities of narcotic addicts in three different metropolitan areas, male narcotic addicts attending methadone maintenance/detoxification centers in Baltimore, Philadelphia, and New York City participated in extensive, confidential interviews conducted between May 1983 and April 1984. The information obtained focused on the amounts and types of crimes committed during the addict's longest period of active addiction to opiates, their derivatives and synthetics, as well as his first period of nonaddiction. Crimes committed were placed in one of five categories as follows: Theft, Violence, Drug Sales, Deception/Forgery, and Other. Several different measures of criminal activity were utilized, all embodying the concept of crime-days per year at risk. Such crime-days measures involve annualizing, i.e., the number of crime-days accumulated by each subject in each category during a specified time at large in the community is expressed as crime-days per year at risk by taking the ratio of crime-days to total days at large and multiplying by 365. Addicts were compared by race/ethnicity (Black, White, and Hispanic) within cities as well as by race/ethnicity across cities using one-way analysis of variance procedures. Addict crime rates were also compared for the period of active addiction and nonaddiction. Several mean differences by race/ethnicity within city, as well as by race across cities, were noted. Moreover, crime rates tended to be higher during the period of active addiction. In this sense, then, drugs may be said to "drive" crime.     

What Risk Factors Are Associated With Musculoskeletal Injury in US Army Rangers? A Prospective Prognostic Study

Background

Musculoskeletal injury is the most common reason that soldiers are medically not ready to deploy. Understanding intrinsic risk factors that may place an elite soldier at risk of musculoskeletal injury may be beneficial in preventing musculoskeletal injury and maintaining operational military readiness. Findings from this population may also be useful as hypothesis-generating work for particular civilian settings such as law enforcement officers (SWAT teams), firefighters (smoke jumpers), or others in physically demanding professions.

Questions/purposes

The purposes of this study were (1) to examine whether using baseline measures of self-report and physical performance can identify musculoskeletal injury risk; and (2) to determine whether a combination of predictors would enhance the accuracy for determining future musculoskeletal injury risk in US Army Rangers.

Methods

Our study was a planned secondary analysis from a prospective cohort examining how baseline factors predict musculoskeletal injury. Baseline predictors associated with musculoskeletal injury were collected using surveys and physical performance measures. Survey data included demographic variables, injury history, and biopsychosocial questions. Physical performance measures included ankle dorsiflexion, Functional Movement Screen, lower and upper quarter Y-balance test, hop testing, pain provocation, and the Army Physical Fitness Test (consisting of a 2-mile run and 2 minutes of sit-ups and push-ups). A total of 320 Rangers were invited to enroll and 211 participated (66%). Occurrence of musculoskeletal injury was tracked for 1 year using monthly injury surveillance surveys, medical record reviews, and a query of the Department of Defense healthcare utilization database. Injury surveillance data were available on 100% of the subjects. Receiver operator characteristic curves and accuracy statistics were calculated to identify predictors of interest. A logistic regression equation was then calculated to find the most pertinent set of predictors. Of the 188 Rangers (age, 23.3 ± 3.7 years; body mass index, 26.0 ± 2.4 kg/m²) remaining in the cohort, 85 (45.2%) sustained a musculoskeletal injury of interest.

Results

Smoking, prior surgery, recurrent prior musculoskeletal injury, limited-duty days in the prior year for musculoskeletal injury, asymmetrical ankle dorsiflexion, pain with Functional Movement Screen clearing tests, and decreased performance on the 2-mile run and 2-minute sit-up test were associated with increased injury risk. Presenting with one or fewer predictors resulted in a sensitivity of 0.90 (95% confidence interval [CI], 0.83–0.95), and having three or more predictors resulted in a specificity of 0.98 (95% CI, 0.93–0.99). The combined factors that contribute to the final multivariable logistic regression equation yielded an odds ratio of 4.3 (95% CI, 2.0–9.2), relative risk of 1.9 (95% CI, 1.4–2.6), and an area under the curve of 0.64.

Conclusions

Multiple factors (musculoskeletal injury history, smoking, pain provocation, movement tests, and lower scores on physical performance measures) were associated with individuals at risk for musculoskeletal injury. The summation of the number of risk factors produced a highly sensitive (one or less factor) and specific (three or more factors) model that could potentially be used to effectively identify and intervene in those persons with elevated risk for musculoskeletal injury. Future research should establish if screening and intervening can improve musculoskeletal health and if our findings among US Army Rangers translate to other occupations or athletes.

Level of Evidence

Level II, prognostic study.     

Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients

Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis.