The relationship between processes and outcomes for injured older adults: a study of a statewide trauma system.

PURPOSE: Age is a risk factor for death, adverse outcomes, and health care use following trauma. The American College of Surgeons' Trauma Quality Improvement Program (TQIP) has published "best practices" of geriatric trauma care; adoption of these guidelines is unknown. We sought to determine which evidence-based geriatric protocols, including TQIP guidelines, were correlated with decreased mortality in Pennsylvania's trauma centers. METHODS: PA's level I and II trauma centers self-reported adoption of geriatric protocols. Survey data were merged with risk-adjusted mortality data for patients ≥65 from a statewide database, the Pennsylvania Trauma Systems Foundation (PTSF), to compare mortality outlier status and processes of care. Exposures of interest were center-specific processes of care; outcome of interest was PTSF mortality outlier status. RESULTS: 26 of 27 eligible trauma centers participated. There was wide variation in care processes. Four trauma centers were low outliers; three centers were high outliers for risk-adjusted mortality rates in adults ≥65. Results remained consistent when accounting for center volume. The only process associated with mortality outlier status was age-specific solid organ injury protocols (p = 0.04). There was no cumulative effect of multiple evidence-based processes on mortality rate (p = 0.50). CONCLUSIONS: We did not see a link between adoption of geriatric best-practices trauma guidelines and reduced mortality at PA trauma centers. The increased susceptibility of elderly to adverse consequences of injury, combined with the rapid growth rate of this demographic, emphasizes the importance of identifying interventions tailored to this population. LEVEL OF EVIDENCE: III. STUDY TYPE: Descriptive.

Penetrating torso injuries in older adults: increased mortality likely due to "failure to rescue".

PURPOSE: Approximately 8 % of injuries in the elderly are from penetrating mechanisms. The natural history of potentially survivable penetrating torso wounds in the elderly is not well studied. Older adults with penetrating injuries to the torso may have worse outcomes than matched, younger patients due to a failure to rescue after complications. METHODS: A retrospective chart review of all patients ≥55 (older) with a penetrating injury (GSW or SW) to the torso over 20 years was performed. All patients with a maximum AIS chest or abdomen >1 and <6 were included. A matched cohort (mechanism, AIS chest and abdomen, ISS and sex) of patients between the ages of 20-40 years (young) was created (3 young, 1 older). Differences in hemodynamics, complications, length of stay and mortality were analyzed. RESULTS: 105 older met inclusion criteria were compared to 315 young patients. Hemodynamic status was similar between the groups. Older patients required ICU care more often than younger patients, p < 0.05. Older patients required longer ICU stays, p < 0.001 and longer hospitalizations, p = 0.0012. More older patients (41.0 %) suffered post-injury complications compared to the young (26.4 %), p = 0.005. Older patients who suffered a complication had a higher mortality (30.2 %) than the young after a complication (10.8 %), p = 0.007. CONCLUSIONS: While uncommon, penetrating injuries to older adults are associated with higher rates of post-injury complications and increased mortality. This may represent a "failure to rescue" and represent an opportunity for improved post-injury care in older adults who suffer potentially survivable penetrating torso injuries.

Initial venous lactate levels in patients with isolated penetrating extremity trauma: a retrospective cohort study.

INTRODUCTION: Elevated initial lactate levels have been shown to be associated with severe injury in trauma patients, but some patients who do not appear to be in shock also presented with elevated lactate levels. We hypothesized that in hemodynamically stable patients with isolated penetrating extremity trauma, initial lactate level does not predict clinically significant bleeding. METHODS: A 5-year institutional database review was performed. Hemodynamically stable patients (HR < 101, SBP > 90) with isolated penetrating extremity trauma with an initial lactate sent were included. The exposure of interest was captured as a dichotomous variable by initial lactate level normal (N ≤ 2.2 mEq/L), elevated (E > 2.2 mEq/L). The primary outcome measurement was clinically significant bleeding, defined by need for intervention (operation, angioembolization, or transfusion) or laboratory evidence of bleeding (presenting Hg < 7 g/dL, or Hg decrease by >2 g/dL/24 h). Chi-squared and Mann-Whitney tests were used to compare variables. RESULTS: A total of 132 patients were identified. There were no differences in demographics or mechanism of injury between the N (n = 43, 7%) and E (n = 89, 14%) groups. Median lactate levels were 1.6 (IQR 1.2-1.9) mEq/dL vs. 3.8 (IQR 2.8-5.2) in the N and E groups, p < 0.001. Lactate was elevated in 89 (67%) patients but was not associated with clinically significant bleeding (37% elevated vs. 39 % not elevated p = 0.82). CONCLUSIONS: In hemodynamically stable patients with isolated penetrating trauma to the extremity, elevated initial venous lactate levels (>2.2 mEq/L) are not associated with bleeding or need for interventions. Clinical judgment remains the gold standard for evaluation and management of these patients.

Cardiotonic steroids induce anti-angiogenic and anti-proliferative profiles in first trimester extravillous cytotrophoblast cells.

OBJECTIVE: Preeclampsia (preE), is characterized by abnormal placental invasion and function. Marinobufagenin (MBG), a cardiotonic steroid (CTS), inhibits cytotrophoblast (CTB) cell functions that are critical for normal placental development. This study tests the hypothesis that CTSs induce anti-angiogenic and anti-proliferative effects in CTB cells. METHODS: Human extravillous CTB cells of the line Sw-71, derived from first trimester chorionic villus tissue, were incubated with 0, 0.1, 1, 10, and 100 nM of each of three CTSs (MBG, cinobufatalin (CINO) and ouabain (OUB)) for 48 h. Thereafter, levels of pro-angiogenic (vascular endothelial growth factor (VEGF165), placental growth factor (PlGF)) and anti-angiogenic (soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng)) factors were measured in culture media using ELISA kits. Expression of three receptors (VEGF receptor 1 (VEGFR1), angiogenic angiotensin type 1 receptor (AT1) and anti-angiogenic angiotensin type 2 receptor (AT2)) were assayed using immunoblotting (western blots) in cell lysates. RESULTS: sFlt-1 and sEng secretion were increased while VEGF165 and PIGF were decreased in the culture media of CTB cells treated with 1 nM or more of each CTSs (p < 0.01 for each). The AT2 receptor expression was up-regulated (p < 0.05) in CTB cells treated with 1 nM or more of MBG and CINO and with 100 nM OUB, while AT1 and VEGFR1 expressions decreased (p < 0.05) with 1 nM or more of MBG and 10 nM or more of CINO and OUB. CONCLUSIONS: CTSs influence extravillous CTB cells to induce an anti-angiogenic and anti-proliferative profile.

The onset of hyperreflexia in the rat following complete spinal cord transection.

STUDY DESIGN: Hyperreflexia occurs after spinal cord injury (SCI) and can be assessed by measuring low frequency-dependent depression of the H-reflex. Previous studies showed the time course for the onset of hyperreflexia to occur between 6-28 days in the contusion model of SCI. OBJECTIVE: To determine the time course of the onset of hyperreflexia in the transection model of SCI and examine changes in Connexin-36 (Cx-36) protein levels in the lumbar enlargement of animals. SETTING: Spinal Cord Injury Mobilization Program of the Center for Translational Neuroscience, the research arm of the Jackson T. Stephens Neuroscience Institute, Little Rock, AR, USA. METHODS: Adult female rats underwent transection at T10 level. Low frequency-dependent depression of the H-reflex was tested at 7, 14 and 30 days post-transection. Lumbar enlargement tissue was harvested following reflex testing and western blots were performed after immunoprecipitation to compare Cx-36 protein levels. RESULTS: Significant decreases in low frequency-dependent depression of the H-reflex were observed in animals tested 14 and 30 days post-transection compared with control animals, but it was not different from control animals at 7 days. Significant decreases in Cx-36 protein levels were observed in animals 7 days post-transection compared with controls. CONCLUSION: Rats transition to a state of hyperreflexia between 7 and 14 days post-transection. Cx-36 protein levels decreased at 7 days post-transection and gradually returned to control levels by 30 days post-transection. These data suggest there may be a relationship between changes in neuronal gap junction protein levels and the delayed onset of hyperreflexia.

Sequence variation between the mouse and human glucose-6-phosphatase catalytic subunit gene promoters results in differential activation by peroxisome proliferator activated receptor gamma coactivator-1alpha.

AIMS/HYPOTHESIS: The glucose-6-phosphatase catalytic subunit (G6PC) plays a key role in hepatic glucose production by catalysing the final step in gluconeogenesis and glycogenolysis. Peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha) stimulates mouse G6pc-luciferase fusion gene expression through hepatocyte nuclear factor-4alpha (HNF-4alpha), which binds an element located between -76 and -64 in the promoter. The aim of this study was to compare the regulation of mouse G6pc and human G6PC gene expression by PGC-1alpha. METHODS: PGC-1alpha action was analysed by transient transfection and gel retardation assays. RESULTS: In H4IIE cells, PGC-1alpha alone failed to stimulate human G6PC-luciferase fusion gene expression even though the sequence of the -76 to -64 HNF-4alpha binding site is perfectly conserved in the human promoter. This difference could be explained, in part, by a 3 bp sequence variation between the mouse and human promoters. Introducing the human sequence into the mouse G6pc promoter reduced PGC-1alpha-stimulated fusion gene expression, whereas the inverse experiment, in which the mouse sequence was introduced into the human G6PC promoter, resulted in the generation of a G6PC-luciferase fusion gene that was now induced by PGC-1alpha. This critical 3 bp region is located immediately adjacent to a consensus nuclear hormone receptor half-site that is perfectly conserved between the mouse G6pc and human G6PC promoters. Gel retardation experiments revealed that this 3 bp region influences the affinity of HNF-4alpha binding to the half-site. CONCLUSIONS/INTERPRETATION: These observations suggest that PGC-1alpha may be more important in the control of mouse G6pc than human G6PC gene expression.

Gestational diabetes screening in subsequent pregnancies of previously healthy patients.

OBJECTIVE: Our purpose was to evaluate women without gestational diabetes mellitus in an index pregnancy for the likelihood that gestational diabetes would develop and for risk factors for carbohydrate intolerance in a subsequent pregnancy. STUDY DESIGN: A retrospective review of medical records at a teaching hospital universally screening for gestational diabetes identified multiparous women who had been delivered twice between 1994 and 1997 and who, in the first (index) pregnancy, had had a normal result on a screening test with 50 g of glucose used in a "glucola" beverage (< or =140 mg/dL). RESULTS: In this population with normal glucose screening values in the index pregnancy, 352 (92.4%) of 381 women had at least one risk factor for gestational diabetes. However, none of the 381 women had gestational diabetes in the subsequent pregnancy (0/381, 95% confidence interval < or =1%), including 45 (12. 4%) who had an abnormal result on the 50-g glucose screening test. Regression analysis showed this test result in the index pregnancy (P =.001) to be the only studied variable significantly associated with the 50-g glucose value in the subsequent pregnancy. CONCLUSION: Despite a high rate of risk factors for gestational diabetes, women in our population with a normal glucose value in an index pregnancy have a minimal risk (<1%) that gestational diabetes will develop in a subsequent singleton pregnancy within 4 years. This factor may be included in determining whether women should undergo screening for gestational diabetes.

The papanicolaou smear: inadequate screening test for bacterial vaginosis during pregnancy.

OBJECTIVE: Our purpose was to evaluate the ability of the Papanicolaou smear to identify bacterial vaginosis in comparison with the Amsel clinical criteria. STUDY DESIGN: We retrospectively identified 159 pregnant women screened for bacterial vaginosis with the Amsel criteria who had a contemporaneous Papanicolaou smear and negative results on screening for Chlamydia trachomatis and Neisseria gonorrhoeae. Bacterial vaginosis was identified in 45 women. We used the McNemar chi(2) test to determine discrepancies between the two screening methods for the detection of bacterial vaginosis. RESULTS: Compared with the Amsel criteria, the sensitivity and specificity of the Papanicolaou smear for yielding a diagnosis of bacterial vaginosis were 49% (95% confidence interval, 36%-64%) and 93% (95% confidence interval, 86%-97%), respectively, with a positive predictive value of 73% and a negative predictive value of 82%. The detection of bacterial vaginosis by Papanicolaou smear was significantly different from that by Amsel criteria (P =. 01). CONCLUSION: The Papanicolaou smear is not a reliable screening test for bacterial vaginosis during pregnancy.

Effects of acute ethanol on indices of cognitive-behavioral performance in rats.

The present experiment examined the effects of ethanol on several complex operant behaviors in rats. Tasks included: temporal response differentiation (TRD) to assess timing behavior; differential reinforcement of low response rates (DRL) to assess timing and response inhibition; incremental repeated acquisition (IRA) to assess learning; conditioned position responding (CPR) to assess auditory, visual, and position discrimination; and progressive ratio (PR) to assess motivation. Ethanol (0.0, 0.5, 1.0, 1.5, 2.0, and 3.0 g/kg via orogastric gavage) reduced accuracy and/or percent task completed for the TRD, DRL, and CPR tasks. For CPR, this reduction was accompanied by a reduction in response rates. Ethanol also reduced response rates on the PR task. There were no effects of ethanol on IRA performance. These data suggest that ethanol can selectively impair performance on cognitive-behavioral tasks and that these effects can occur at doses that do not affect the subjects' ability to respond.

Jelly beans as an alternative to a fifty-gram glucose beverage for gestational diabetes screening.

OBJECTIVE: This study tested the hypothesis that a standardized dose of jelly beans could be used as an alternative sugar source to the 50-g glucose beverage to screen for gestational diabetes mellitus. STUDY DESIGN: One hundred sixty pregnant women at 24 to 28 weeks' gestation were recruited for a prospective study to compare 2 sugar sources for serum glucose response, side effects, preference, and ability to detect gestational diabetes mellitus. Patients were randomly assigned to consume 50-g glucose beverage or 28 jelly beans (50 g simple carbohydrate). Serum glucose values were determined 1 hour later. The test was later repeated with the other sugar source. Finally, a 100-g 3-hour oral glucose tolerance test was performed. Participants completed a questionnaire recording subjective outcome variables. American Diabetes Association criteria were used to interpret all test results. RESULTS: Among 136 participants completing the study no significant differences were found between 1-hour serum glucose values (116.5 +/- 27 mg/dL with 50-g glucose beverage, 116.9 +/- 23.6 mg/dL with jelly beans; P =.84), frequency of discrepant results (P =.47), sensitivity, specificity, or predictive value. Jelly beans yielded fewer side effects (38% with 50-g glucose beverage, 20% with jelly beans; P <.001) and were preferred by 76% of participants (P <.001). Five cases (3.7% incidence) of gestational diabetes mellitus were diagnosed, 3 with 50-g glucose beverage alone, 1 with jelly beans alone, and 1 with both sugar sources. CONCLUSIONS: Jelly beans may be used as an alternative to the 50-g glucose beverage as a sugar source for gestational diabetes mellitus screening. The 2 sources provoke similar serum glucose responses. Patients report fewer side effects after a jelly bean challenge than after a 50-g glucose beverage challenge.

Tocolytic therapy in preterm PROM.

Preterm premature rupture of the membranes nearly always leads to preterm labor and delivery. Preterm delivery accounts for most of the morbidity attributable to PPROM. Antibiotic and corticosteroid treatment may modify the outcome of pregnancy after PPROM. The extent of morbidities attributable to PPROM also justifies consideration of the use of tocolysis, at least for a limited period of time (48 hours) after preterm amniorrhexis. When begun after the onset of contractions following PPROM, tocolysis generally does not prolong the latency period, although some prolongation may occur before 28 weeks gestational age. Prophylactic tocolysis begun before the onset of labor increases the likelihood of delaying the onset of labor for 1-2 days, but not beyond. Aggressive long-term tocolysis may increase the maternal risk of chorioamnionitis and endometritis. None of the reviewed randomized studies demonstrated a significant neonatal risk. None of these studies showed an improvement in neonatal outcome, although they have not tested the combination of tocolysis and corticosteroid use with appropriate controls. The hypothesis that PROM remote from term should be managed with 1-2 days of prophylactic tocolysis and corticosteroids to enhance fetal pulmonary maturity is attractive, yet it remains inadequately evaluated.

Management of asymptomatic term neonates whose mothers received intrapartum antibiotics--Part 2: Diagnostic tests and management strategies. Center of Disease Control and Prevention.

The evaluation of the potentially septic newborn is often a source of frustration for practitioners. In the past, it has often been standard practice to evaluate and treat empirically all neonates whose mothers received antibiotics during labor, regardless of whether the infant had any signs or symptoms suggestive of infection. With the advent of recommendations for intrapartum antibiotic therapy to prevent early-onset neonatal group B streptococcal infections, this strategy is no longer practicable because too many infants would thus be evaluated and treated needlessly. This two-part review addresses the issues involved in managing asymptomatic newborns whose mothers received intrapartum antibiotics. Part I, published separately, reviewed the rationale behind strategies for preventing intrapartum transmission of bacterial infection. This final part addresses the evaluation and management of the newborn. A number of diagnostic tests are often used in looking for bacterial infections in the neonate. Unfortunately, none of these is both rapid and reliable. A clinical pathway provided here can serve as a useful guide for the clinician, but uncertainty will always remain. Ultimately, each practitioner must determine the degree of risk or uncertainty that he or she can accept on the basis of clinical experience.

Personal illness models of diabetes: parents of preadolescents and adolescents.

The purpose of this research was to explore personal illness models of parents of preadolescents and adolescents regarding diabetes mellitus. Personal illness models were defined as the parents' cognitive representations of the disease. Fifty-five parents of children ages 10 to 17 years with a diagnosis of insulin-dependent diabetes mellitus were interviewed using a semistructured questionnaire. Data were content analyzed for common themes. Parents attributed the cause of diabetes to genetics coupled with a viral infection. Most believed the diabetes would last a lifetime but they were hopeful for a cure. Parents requested ongoing education for their children, support groups, counseling, one consistent healthcare provider, and intensive insulin therapy. Parents reported that the major problems caused by diabetes were increased structure of daily routines and that their children with diabetes felt different from healthy peers. Parents' fears about diabetes included long-term complications, early death, and severe insulin reactions.

Management of asymptomatic term neonates whose mothers received intrapartum antibiotics--Part 1: Rationale for intrapartum antibiotic therapy.

The evaluation of the potentially septic newborn is often a source of frustration for practitioners. In the past, it has often been standard practice to evaluate and treat empirically all neonates whose mothers received antibiotics during labor, regardless of whether the infant had any signs or symptoms suggestive of infection. With the advent of recommendations for intrapartum antibiotic therapy to prevent early-onset neonatal group B streptococcal infections, this strategy is no longer practicable because too many infants would thus be evaluated and treated needlessly. This two-part review addresses the issues involved in managing asymptomatic newborns whose mothers received intrapartum antibiotics. This first part reviews the rationale behind strategies for preventing intrapartum transmission of bacterial infection. The administration of intravenous antibiotics to laboring mothers appears to reduce the incidence of group B streptococcal infections in neonates. Additionally, intrapartum antibiotic therapy for maternal chorioamnionitis may inhibit transmission of infection to the infant. Part 2--to be published separately--will address the evaluation and management of the newborn.

Personal illness models of diabetes: preadolescents and adolescents.

The purpose of this research study was to explore personal illness models of preadolescents and adolescents regarding diabetes mellitus. Personal illness models were defined as the adolescents' cognitive representations of their disease. Sixty children ages 10 to 17 years with a diagnosis of insulin-dependent diabetes mellitus were interviewed using a semistructured questionnaire. Data were content analyzed for common themes. Although most participants expressed an understanding that their disease would last a lifetime, they were hopeful for a cure. Participants wanted healthcare professionals to provide strategies for controlling blood glucose to prevent future complications. Family and friends who followed the same diet as the adolescent with diabetes were viewed as supportive. The majority of adolescents were responsible for much of their own disease management. Their greatest fears concerned insulin reactions and long-term complications such as amputation of limbs.

Co-induction of anaesthesia: the rationale.

Combination therapy with two or more different drugs, with the intention of reaching the same therapeutic goal, was heavily criticized for a long time. However, it is accepted today, especially when advantages over monotherapy can be shown. For the induction of anaesthesia or for long-term sedation in the intensive care unit, combination therapy may offer an improved effect profile, a more balanced ratio of desired versus adverse effects, an improved time-course of effect, simpler treatment requirements or lower costs. Midazolam and propofol have been investigated as potential partners for those two indications. The mechanism of action, pharmacokinetic properties, pharmacological effect, the way in which they interact at the receptor site, the differences in pharmaceutical formulations, the side-effect profiles and economic considerations were compared. Animal experiments and clinical pharmacology studies have shown that midazolam and propofol have synergy with other centrally active drugs. It could be expected that the relationship between desired effects and adverse effects could be improved by skilful use of the synergism between midazolam and propofol. Co-induction of anaesthesia and co-administration in long-term sedation can offer improvements in therapeutic situations compared with monotherapy. These improvements are in terms of a more suitable effect profile, a more favourable ratio of desirable effects to side-effects, optimization of the time-course of effects and reduced costs.

Stability of the WAIS-R and WISC-III factor structure using cross-validation of covariance structures.

The stability of the Verbal Comprehension, Perceptual Organization, and Freedom from Distractibility factors of the WAIS-R and WISC-III was tested using cross-validation of covariance structure models, a methodology that employs unrestricted and restricted factor analyses. Stability was indicated if the goodness of fit of restricted models generated from unrestricted factor patterns did not degrade when applied to other age groups. If goodness of fit degraded inconsistently, the factor structure of one or both instruments was unreliable. If goodness of fit changed in some systematic fashion, an argument for true intellectual changes could be made. Results indicated consistency across age groups. Therefore, it was concluded that the three-factor structure is robust and reliable across age groups and instruments.