James J. Grady

Efficacy of hypertonic 7.5% saline and 6% dextran-70 in treating trauma: A meta-analysis of controlled clinical studies

BACKGROUND Individual trials of small-volume resuscitation of 7.5% NaCl (HS) with and without 6% dextran 70 (HSD) for the treatment of trauma have failed to provide convincing evidence of efficacy. We performed a meta-analysis to evaluate the effects of HS and HSD on survival until discharge or for 30 days. We identified eight double-blinded, randomized controlled trials of HSD and six trials of HS. In all cases, administration of 250 ml of HSD or HS was compared with a control group administration of 250 ml of isotonic crystalloid for the treatment of hypotension either in the field or at admission to the emergency department. METHODS A fixed-effects meta-analysis was performed with the Mantel-Haenszel method of combining results from multiple studies. RESULTS Overall, HS was not effective in improving survival with a weighted mean difference in survival of the HS group versus the isotonic control group equal to 0.6%. The results with HSD were more positive, with an increase in survival in seven of eight trials. The mean difference in survival rates favoring HSD (n = 615) over controls (n = 618) was 3.5% (p = 0.14, two-tailed; p = 0.07, one-tailed). The odds ratio was estimated to be 1.20 in favor of HSD with a 95% confidence interval of 0.94 to 1.57. CONCLUSIONS The meta-analysis of the available data shows that HS is not different from the standard of care and that HSD may be superior.

Viral upper respiratory tract infection and otitis media complication in young children.

Abstract Background. The common cold or upper respiratory infection (URI) is highly prevalent among young children and often results in otitis media (OM). The incidence and characteristics of OM complicating URI due to specific viruses have not been well studied. Methods. We performed a prospective, longitudinal cohort study of 294 healthy children (age range, 6 months to 3 years). Each child was observed for 1 year to assess the occurrence of URI, acute OM (AOM), and OM with effusion (OME) complicating URI due to specific viruses. Results. We documented 1295 URI episodes (5.06 episodes per child-year) and 440 AOM episodes (1.72 episodes per child-year). Virus studies were performed for 864 URI episodes; 63% were virus positive. Rhinovirus and adenovirus were most frequently detected during URI. The overall incidence of OM that complicated URI was 61%, including a 37% incidence of AOM and a 24% incidence of OME. Young age was the most important predictor of AOM that complicated URI. AOM occurred in approximately one-half of children with URI due to adenovirus, respiratory syncytial virus, or coronavirus and in approximately one-third of those with URI due to influenza virus, parainfluenza virus, enterovirus, or rhinovirus. Conclusions. More than 60% of episodes of symptomatic URI among young children were complicated by AOM and/or OME. Young age and specific virus types were predictors of URI complicated by AOM. For young children, the strategy to prevent OM should involve prevention of viral URI. The strategy may be more effective if the priority is given to development of means to prevent URI associated with adenovirus and respiratory syncytial virus.

Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension

BACKGROUND Resuscitation with hypertonic saline/dextran (HSD) has been suggested to be efficacious in patients who have traumatic brain injury and are hypotensive. We undertook a cohort analysis of individual patient data from previous prospective randomized double-blinded trials to evaluate improvements in survival at 24 hours and discharge after initial treatment with HSD in patients who had traumatic brain injury (head region Abbreviated Injury Score > or = 4) and hypotension (systolic blood pressure < or = 90 mm Hg). METHODS All variables and end points were defined before initiation of data handling. Investigators were blind as to the treatment. Case report forms were received from six studies. Of these, 223 patients met the inclusion for traumatic brain injury. Comparisons between HSD and standard of care were made using stratified analysis and logistic regression to assess efficacy, confounding, and interaction. Potential confounding variables of pre-fluid treatment, Glasgow Coma Scale score (3-8 vs. 9-15), injury type, and systolic blood pressure can be considered a priori factors that were known before randomization. Effects of the various trials was also considered. RESULTS Treatment with HSD resulted in a survival until discharge of 37.9% (39 of 103) compared with 26.9% (32 of 119) with standard of care (p = 0.080). Using logistic regression, adjusting for trial and potential confounding variables, the treatment effect can be summarized by the odds ratio of 2.12 (p = 0.048) for survival until discharge. CONCLUSIONS Patients who have traumatic brain injuries in the presence of hypotension and receive HSD are about twice as likely to survive as those who receive standard of care.

A case-control study of anatomic changes resulting from sexual abuse.

OBJECTIVE Our goal was to identify vulvar and hymenal characteristics associated with sexual abuse among female children between the ages of 3 and 8 years. STUDY DESIGN Using a case-control study design, we examined and photographed the external genitalia of 192 prepubertal children with a history of penetration and 200 children who denied prior abuse. Bivariate analyses were conducted by chi(2), the Fisher exact test, and the Student t test to assess differences in vulvar and hymenal features between groups. RESULTS Vaginal discharge was observed more frequently in abused children (P =.01). No difference was noted in the percentage of abused versus nonabused children with labial agglutination, increased vascularity, linea vestibularis, friability, a perineal depression, or a hymenal bump, tag, longitudinal intravaginal ridge, external ridge, band, or superficial notch. Furthermore, the mean number of each of these features per child did not differ between groups. A hymenal transection, perforation, or deep notch was observed in 4 children, all of whom were abused. CONCLUSION The genital examination of the abused child rarely differs from that of the nonabused child. Thus legal experts should focus on the childs history as the primary evidence of abuse.

A prospective, controlled study of the effects of hormonal contraception on bone mineral density ☆

OBJECTIVE To compare the effect of depot medroxypro‐gesterone acetate (DMPA) and two types of oral contraceptives (OC) on bone mineral density (BMD) among women 18–33 years of age with those not using hormonal contraception. METHODS Data from 155 women were analyzed. Depot medroxyprogesterone acetate was administered to 33 women; 63 women who chose oral contraception were randomly assigned to receive either a norethindrone‐containing pill (n = 28) or a desogestrel‐containing pill (n = 35). Fifty‐nine women who did not use hormonal contraception served as controls. Lumbar spine BMD was determined using dual‐energy x‐ray absorptiometry at baseline and after 12 months of contraceptive use. We analyzed method‐related percent change in BMD while controlling for body mass index, calcium intake, exercise, and smoking. We had approximately 90% power to detect a 2.5% difference between any two groups. RESULTS Users of DMPA experienced a mean BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37% loss (P = .01). Users of OCs generally demonstrated a gain (2.33% for norethindrone‐containing pills, 0.33% for desogestrel‐containing pills), which was different from controls among users of norethindrone‐containing pills (P = .01), but not among users of desogestrel‐containing pills (P = .99). Observed changes in BMD among DMPA users differed from women who used either type of pill (P < .002). CONCLUSION Depot medroxyprogesterone acetate has an adverse effect on BMD, in comparison with OCs or non‐hormonal methods, when used for 12 months. Results must be interpreted cautiously until it is determined whether these effects endure or are reversible.

Cardiovascular Morbidity Associated with Gonadotropin Releasing Hormone Agonists and an Antagonist

BACKGROUND Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity. OBJECTIVE To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist. DESIGN, SETTING, AND PARTICIPANTS Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist. Men recruited had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 12 mo, and were naïve to ADT. Men were excluded if they had a prolonged baseline QT/corrected QT interval, other risk factors for heart failure, hypokalemia or a family history of long QT syndrome, or had another cancer diagnosed within 5 yr. INTERVENTION Men were randomized to receive a GnRH agonist or an antagonist for either 3-7 mo (n=642) or 12 mo (n=1686). Treatment groups were balanced for common baseline characteristics. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Event analysis was based on death from any cause or cardiac events. Data documenting adverse experiences were classified based on the Medical Dictionary for Regulatory Activities. The following conditions defined a cardiac event: arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease. Kaplan-Meier curves and log-rank tests were used to compare time to a cardiovascular event or death. RESULTS AND LIMITATIONS Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 yr of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26-0.74; p=0.002). Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating. CONCLUSIONS GnRH antagonists appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT when compared to GnRH agonists.

Changing Trends in the Survival of Dialysis Patients with Human Immunodeficiency Virus in the United States

HIV-infected patients with end-stage renal disease have a very high morbidity and mortality. In the last decade, survival of HIV-infected patients in the United States has remarkably improved. To determine whether similar improvement in survival has occurred in HIV-infected dialysis patients, their survival was evaluated by using the United States Renal Data System database. Survival of HIV-infected dialysis patients in the United States was determined and the influence of year of initiation of dialysis, and demographic characteristics on the survival were analyzed by the Kaplan-Meier method. The effects of above variables on survival were also examined in a Cox proportional hazards model. Identified were 6166 HIV-infected patients with end-stage renal disease who received dialysis in the United States. Eighty-nine percent of the patients were black, 7.4% white, and 3% other. From 1990 to 1999, 1-yr survival of HIV-infected patients on dialysis improved from 56 to 74%, and the annual death rates declined from 458 deaths to 240 deaths per 1000 patient-years. The hazard ratio declined significantly in patients who initiated dialysis in years 1999-2000 compared with patients who initiated dialysis < or = 1990 (hazard ratio, 0.49; 95% confidence interval, 0. 40 to 0.60). Survival of HIV-infected dialysis patients has remarkably improved in the United States.

Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients

Previous studies have reported that approximately 10% of the patients with human immunodeficiency virus (HIV) infection develop HIV-associated nephropathy (HIVAN). However, over the last decade, morbidity and mortality as a result of HIV-1 infection has remarkably decreased with the availability of potent new antiretroviral drugs. We therefore determined the prevalence of HIVAN from autopsy data of HIV-infected patients in more recent years (1992 to 1997). Autopsy reports of 389 patients were reviewed. In reports suggestive of possible HIVAN, slides of renal tissue were retrieved and reviewed again to ensure appropriate classification. The criteria for the diagnosis of HIVAN were focal segmental glomerulosclerosis with collapse of the glomerular tuft in some glomeruli, extensive tubular ectasia, and significant tubulointerstitial disease. Of 389 autopsy reports, 54% of the patients were black, 35% were white, and 11% were Hispanic. Thirty-three percent of the patients had a history of intravenous drug abuse. The mean CD4 count of the patients was 54 +/- 91/microL (mean +/- SD). In 27 cases, typical features of HIVAN were found based on the criteria used, accounting for an overall HIVAN prevalence of 6.9% (27 of 389 autopsies). Because the overwhelming majority of these patients were black (93%), the prevalence in blacks was 12% (25 of 209 autopsies). We conclude that although mortality and morbidity from HIV infection is decreasing, HIVAN remains an important complication of HIV infection in blacks, even in recent years.

APRI : An easy and validated predictor of hepatic fibrosis in chronic hepatitis C

Goals To evaluate the aspartate aminotransferase/platelet ratio index (APRI) as a predictor of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis C (HCV). Background The decision to treat HCV is often made on the basis of the presence or absence of significant fibrosis on the liver biopsy. Because liver biopsy is expensive and invasive a noninvasive marker to evaluate hepatic fibrosis would be useful. The APRI is an easy to calculate index that is one of several markers that have been proposed. Study We retrospectively reviewed the charts of 339 patients with chronic HCV who had liver biopsies from January 2000 to March 2003. We subsequently evaluated 151 patients receiving pretreatment evaluation liver biopsies who had serum aspartate aminotransferase, platelets, routine liver function tests, and demographic data obtained. All liver biopsies were staged by the Batts Ludwig criteria. Results The area under the curve of the receiver operator characteristics of the calculated APRI compared with the liver biopsy demonstrated that the fibrosis score was 0.889 in the prospective group and 0.790 in the retrospective group. To achieve predictive values of approximately 90%, useful cutoffs were found at 0.40 and 1.5 in the retrospective study, and 0.42 and 1.2 in the prospective study leaving intermediate zones of 58.9% and 41.1%, respectively. In the prospective group, 34 of 36 patients with a value of <0.42 were accurately predicted as having mild fibrosis, whereas 50 of 54 patients with a value >1.2 were accurately predicted to have significant fibrosis. Conclusions The APRI is a good estimator of hepatic fibrosis and was more accurate in a prospective group than a retrospective one. It potentially could be used to decrease the number of liver biopsies.

Incidence of Acute Otitis Media and Sinusitis Complicating Upper Respiratory Tract Infection: The Effect of Age

Infants and young children are prone to developing upper respiratory tract infections, which often result in bacterial complications such as acute otitis media and sinusitis. We evaluated 623 upper respiratory tract infection episodes in 112 children (6–35 months of age) to determine the proportion of upper respiratory tract infection episodes that result in acute otitis media or sinusitis. Of all upper respiratory tract infections, 30% were complicated by acute otitis media and 8% were complicated by sinusitis. The rate of acute otitis media after upper respiratory tract infection declined with increasing age, whereas the rate of sinusitis after upper respiratory tract infection peaked in the second year of life. Risk for acute otitis media may be reduced substantially by avoiding frequent exposure to respiratory viruses (eg, avoidance of day care attendance) in the first year of life.