Preconception care: promoting reproductive planning.

INTRODUCTION: Preconception care recognizes that many adolescent girls and young women will be thrust into motherhood without the knowledge, skills or support they need. Sixty million adolescents give birth each year worldwide, even though pregnancy in adolescence has mortality rates at least twice as high as pregnancy in women aged 20-29 years. Reproductive planning and contraceptive use can prevent unintended pregnancies, unsafe abortions and sexually-transmitted infections in adolescent girls and women. Smaller families also mean better nutrition and development opportunities, yet 222 million couples continue to lack access to modern contraception. METHOD: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Comprehensive interventions can prevent first pregnancy in adolescence by 15% and repeat adolescent pregnancy by 37%. Such interventions should address underlying social and community factors, include sexual and reproductive health services, contraceptive provision; personal development programs and emphasizes completion of education. Appropriate birth spacing (18-24 months from birth to next pregnancy compared to short intervals <6 months) can significantly lower maternal mortality, preterm births, stillbirths, low birth weight and early neonatal deaths. CONCLUSION: Improving adolescent health and preventing adolescent pregnancy; and promotion of birth spacing through increasing correct and consistent use of effective contraception are fundamental to preconception care. Promoting reproductive planning on a wider scale is closely interlinked with the reliable provision of effective contraception, however, innovative strategies will need to be devised, or existing strategies such as community-based health workers and peer educators may be expanded, to encourage girls and women to plan their families.

Preconception care: nutritional risks and interventions.

INTRODUCTION: There is increasingly a double burden of under-nutrition and obesity in women of reproductive age. Preconception underweight or overweight, short stature and micronutrient deficiencies all contribute to excess maternal and fetal complications during pregnancy. METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on maternal, newborn and child health (MNCH) outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Maternal pre-pregnancy weight is a significant factor in the preconception period with underweight contributing to a 32% higher risk of preterm birth, and obesity more than doubling the risk for preeclampsia, gestational diabetes. Overweight women are more likely to undergo a Cesarean delivery, and their newborns have higher chances of being born with a neural tube or congenital heart defect. Among nutrition-specific interventions, preconception folic acid supplementation has the strongest evidence of effect, preventing 69% of recurrent neural tube defects. Multiple micronutrient supplementation shows promise to reduce the rates of congenital anomalies and risk of preeclampsia. Although over 40% of women worldwide are anemic in the preconception period, only one study has shown a risk for low birth weight. CONCLUSION: All women, but especially those who become pregnant in adolescence or have closely-spaced pregnancies (inter-pregnancy interval less than six months), require nutritional assessment and appropriate intervention in the preconception period with an emphasis on optimizing maternal body mass index and micronutrient reserves. Increasing coverage of nutrition-specific and nutrition-sensitive strategies (such as food fortification; integration of nutrition initiatives with other maternal and child health interventions; and community based platforms) is necessary among adolescent girls and women of reproductive age. The effectiveness of interventions will need to be simultaneously monitored, and form the basis for the development of improved delivery strategies and new nutritional interventions.

Preconception care: preventing and treating infections.

INTRODUCTION: Infections can impact the reproductive health of women and hence may influence pregnancy related outcomes for both the mother and the child. These infections range from sexually transmitted infections (STIs) to TORCHS infections to periodontal disease to systemic infections and may be transmitted to the fetus during pregnancy, labor, delivery or breastfeeding. METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Preconception behavioral interventions significantly declines re-infection or new STI rates by 35% (95% CI: 20-47%). Further, condom use has been shown to be the most effective way to prevent HIV infection (85% protection in prospective studies) through sexual intercourse. Intervention trials showed that preconception vaccination against tetanus averted a significant number of neonatal deaths (including those specifically due to tetanus) when compared to placebo in women receiving more than 1 dose of the vaccine (OR 0.28; 95% CI: 0.15-0.52); (OR 0.02; 95% CI: 0.00-0.28) respectively. CONCLUSION: Preconception counseling should be offered to women of reproductive age as soon as they test HIV-positive, and conversely women of reproductive age should be screened with their partners before pregnancy. Risk assessment, screening, and treatment for specific infections should be a component of preconception care because there is convincing evidence that treatment of these infections before pregnancy prevents neonatal infections.

Preconception care: screening and management of chronic disease and promoting psychological health.

INTRODUCTION: A large proportion of women around the world suffer from chronic diseases including mental health diseases. In the United States alone, over 12% of women of reproductive age suffer from a chronic medical condition, especially diabetes and hypertension. Chronic diseases significantly increase the odds for poor maternal and newborn outcomes in pregnant women. METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for preventing and managing chronic diseases and promoting psychological health on maternal, newborn and child health outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Maternal prepregnancy diabetic care is a significant intervention that reduces the occurrence of congenital malformations by 70% (95% Confidence Interval (CI): 59-78%) and perinatal mortality by 69% (95% CI: 47-81%). Furthermore, preconception management of epilepsy and phenylketonuria are essential and can optimize maternal, fetal and neonatal outcomes if given before conception. Ideally changes in antiepileptic drug therapy should be made at least 6 months before planned conception. Interventions specifically targeting women of reproductive age suffering from a psychiatric condition show that group-counseling and interventions leading to empowerment of women have reported non-significant reduction in depression (economic skill building: Mean Difference (MD) -7.53; 95% CI: -17.24, 2.18; counseling: MD-2.92; 95% CI: -13.17, 7.33). CONCLUSION: While prevention and management of the chronic diseases like diabetes and hypertension, through counseling, and other dietary and pharmacological intervention, is important, delivering solutions to prevent and respond to women's psychological health problems are urgently needed to combat this leading cause of morbidity.

Preconception care: caffeine, smoking, alcohol, drugs and other environmental chemical/radiation exposure.

INTRODUCTION: As providing health education, optimizing nutrition, and managing risk factors can be effective for ensuring a healthy outcome for women and her yet un-conceived baby, external influences play a significant role as well. Alcohol, smoking, caffeine use and other similar lifestyle factors, have now become an integral part of the daily life of most men and women, who use/misuse one or more of these harmful substances regularly despite knowledge of their detrimental effects. The adverse health outcomes of these voluntary and involuntary exposures are of even greater concern in women of child bearing age where the exposure has the potential of inflicting harm to two generations. This paper is examining the available literature for the possible effects of caffeine consumption, smoking, alcohol or exposure to chemicals may have on the maternal, newborn and child health (MNCH). METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception usage of caffeine, tobacco, alcohol and other illicit drugs; and exposure to environmental chemicals and radiant on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Heavy maternal preconception caffeine intake of >300 mg/d significantly increase the risk of a subsequent fetal loss by 31% (95% CI: 8-58%). On the other hand, preconception alcohol consumption leads to non-significant 30% increase in spontaneous abortion (RR 1.30; 95% CI: 0.85-1.97). Preconception counselling can lead to a significant decrease in the consumption of alcohol during the first trimester (OR 1.79; 95% CI: 1.08-2.97). Periconception smoking, on the other hand, was found to be associated with an almost 3 times increased risk of congenital heart defects (OR 2.80; 95% CI 1.76-4.47). While the review found limited evidence of preconception environmental exposure on maternal, newborn and child health outcomes, occupational exposure in female radiation workers before conception showed an increased impact in risk of early miscarriages. CONCLUSION: Identification of substance abuse and environmental history during preconception period provides an opportunity to assist women in reducing major health risks and identify key determinants of healthy pregnancy. Studies have shown that the aversion and prevention of exposure feasibility can play an important role in improving the health of women and their families, however, the results should be interpreted with great caution as there were few studies in each section. Therefore, there is a need for more rigorous studies to test the hypotheses.

Preconception care: closing the gap in the continuum of care to accelerate improvements in maternal, newborn and child health.

INTRODUCTION: Preconception care includes any intervention to optimize a woman's health before pregnancy with the aim to improve maternal, newborn and child health (MNCH) outcomes. Preconception care bridges the gap in the continuum of care, and addresses pre-pregnancy health risks and health problems that could have negative maternal and fetal consequences. It therefore has potential to further reduce global maternal and child mortality and morbidity, especially in low-income countries where the highest burden of pregnancy-related deaths and disability occurs. METHODS: A systematic review and meta-analysis of the evidence was conducted to ascertain the possible impact of preconception care for adolescents, women and couples of reproductive age on MNCH outcomes. A comprehensive strategy was used to search electronic reference libraries, and both observational and clinical controlled trials were included. Cross-referencing and a separate search strategy for each preconception risk and intervention ensured wider study capture. RESULTS: Women who received preconception care in either a healthcare center or the community showed improved outcomes, such as smoking cessation; increased use of folic acid; breastfeeding; greater odds of obtaining antenatal care; and lower rates of neonatal mortality. CONCLUSION: Preconception care is effective in improving pregnancy outcomes. Further studies are needed to evaluate consistency and magnitude of effect in different contexts; develop and assess new preconception interventions; and to establish guidelines for the provision of preconception care.

Differential effects of fresh frozen plasma and normal saline on secondary brain damage in a large animal model of polytrauma, hemorrhage and traumatic brain injury.

BACKGROUND: We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock. METHODS: Yorkshire swine (n = 10) underwent Grade III liver injury, rib fracture, standardized TBI, and volume-controlled hemorrhage, (40% ± 5%) and were randomly resuscitated with either FFP or normal saline. Hemodynamic parameters and brain oxygenation were continuously monitored, while microdialysis was used to measure the brain concentrations of pyruvate, lactate, glutamate, and glycerol at baseline; 1 hour and 2 hours after shock; immediate postresuscitation (PR); as well as 2, 4, and 6 hours PR. Cells from the injured hemisphere were separated into mitochondrial and cytosolic fractions and analyzed for activity of the pyruvate dehydrogenase complex (PDH). RESULTS: There were no baseline differences in cerebral perfusion pressure, brain oxygenation, as well as concentrations of pyruvate, lactate, glutamate, and glycerol between the groups. At 2 hours and 4 hours PR, the FFP group had significantly higher cerebral perfusion pressures (52 [5] mm Hg vs. 43 [2] mm Hg, p = 0.016; and 50 [7] mm Hg vs. 37 [1] mm Hg, p = 0.008, respectively). There was a sustained and significant (p < 0.05) drop in the glutamate and glycerol levels in the FFP group, implying a decrease in excitotoxicity and brain damage, respectively. Mitochondrial PDH activity was significantly higher (2,666.2 [638.2] adjusted volume INT × mm vs. 1,293.4 [88.8] adjusted volume INT × mm, p = 0.008), and cytosolic PDH activity was correspondingly lower (671.4 [209.2] adjusted volume INT × mm vs. 3070.7 [484.3] adjusted volume INT × mm, p < 0.001) in the FFP group, suggesting an attenuation of mitochondrial dysfunction and permeability. CONCLUSION: In this model of TBI, polytrauma, and hemorrhage, FFP resuscitation confers neuroprotection by improving cerebral perfusion, diminishing glutamate-mediated excitotoxic secondary brain injury and reducing mitochondrial dysfunction.

Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock.

BACKGROUND: Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP. METHODS: Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced (40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured. RESULTS: This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly (p < 0.05) decreased brain lesion size and swelling (51% and 54%, respectively). CONCLUSION: In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages.

Real-time heart rate entropy predicts the need for lifesaving interventions in trauma activation patients.

BACKGROUND: Heart rate complexity (HRC), commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice has been precluded by the absence of real-time data. This study was conducted to evaluate the utility of real-time, automated, instantaneous, hand-held heart rate entropy analysis in predicting the need for lifesaving interventions (LSIs). We hypothesized that real-time HRC would predict LSIs. METHODS: Prospective enrollment of patients who met criteria for trauma team activation was conducted at a Level I trauma center (September 2011 to February 2012). A novel, hand-held, portable device was used to measure HRC (by sample entropy) and time-domain heart rate variability continuously in real time for 2 hours after the moment of presentation. Electric impedance cardiography was used to determine cardiac output. Patients who received an LSI were compared with patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. RESULTS: Of 82 patients enrolled, 21 (26%) received 67 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. LSI patients had a lower Glasgow Coma Scale (GCS) score (9.2 [5.1] vs. 14.9 [0.2], p < 0.0001). The mean (SD) HRC value on presentation was 0.8 (0.6) in the LSI group compared with 1.5 (0.6) in the non-LSI group (p < 0.0001). With the use of logistic regression, initial HRC was the only significant predictor of LSI. A cutoff value for HRC of 1.1 yields sensitivity, specificity, negative predictive value, and positive predictive value of 86%, 74%, 94%, and 53%, respectively, with an accuracy of 77% for predicting an LSI. CONCLUSION: Decreased HRC on hospital arrival is an independent predictor of the need for LSI in trauma activation patients. Real-time HRC may be a useful adjunct to standard vital signs monitoring and predicts LSIs. LEVEL OF EVIDENCE: Prognostic and diagnostic study, level III.

Excessively long hospital stays after trauma are not related to the severity of illness: let's aim to the right target!

IMPORTANCE: Reduction in length of hospital stay is a veritable target in reducing the overall costs of health care. However, many existing approaches are flawed because the assumptions of what cause excessive length of stay are incorrect; we methodically identified the right targets in this study. OBJECTIVE: To identify the causes of excessively prolonged hospitalization (ExProH) in trauma patients. DESIGN: The trauma registry, billing databases, and medical records of trauma admissions were reviewed. Excessively prolonged hospitalization was defined by the standard method used by insurers, which is a hospital stay that exceeds the Diagnosis Related Group-based trim point. The causes of ExProH were explored in a unique potentially avoidable days database, used by our hospital's case managers to track discharge delays. SETTING: Level I academic trauma center. PARTICIPANTS: Adult trauma patients admitted between January 1, 2006, and December 31, 2010. MAIN OUTCOMES AND MEASURES: Excessively prolonged hospitalization and hospital cost. RESULTS: Of 3237 patients, 155 (5%) had ExProH. The patients with ExProH compared with non-ExProH patients were older (mean [SD] age, 53 [21] vs 47 [22] years, respectively; P = .001), were more likely to have blunt trauma (92% vs 84%, respectively; P = .03), were more likely to be self-payers (16% vs 11%, respectively; P = .02) or covered by Medicare/Medicaid (41% vs 30%, respectively; P = .002), were more likely to be discharged to post-acute care facilities than home (65% vs 35%, respectively; P < .001), and had higher hospitalization cost (mean, $54 646 vs $18 444, respectively; P < .001). Both groups had similar Injury Severity Scores, Revised Trauma Scores, baseline comorbidities, and in-hospital complication rates. Independent predictors of mortality were discharge to a rehabilitation facility (odds ratio = 4.66; 95% CI, 2.71-8.00; P < .001) or other post-acute care facility (odds ratio = 5.04; 95% CI, 2.52-10.05; P < .001) as well as insurance type that was Medicare/Medicaid (odds ratio = 1.70; 95% CI, 1.06-2.72; P = .03) or self-pay (odds ratio = 2.43; 95% CI, 1.35-4.37; P = .003). The reasons for discharge delays were clinical in only 20% of the cases. The remaining discharges were excessively delayed because of difficulties in rehabilitation facility placement (47%), in-hospital operational delays (26%), or payer-related issues (7%). CONCLUSIONS AND RELEVANCE: System-related issues, not severity of illness, prolong hospital stay excessively. Cost-reduction efforts should target operational bottlenecks between acute and postacute care.

Outcomes following "rescue" superselective angioembolization for gastrointestinal hemorrhage in hemodynamically unstable patients.

BACKGROUND: Therapeutic angioembolization is a relatively new "rescue treatment" modality for gastrointestinal hemorrhage (GIH) for unstable patients who fail primary treatment approaches; however, the effectiveness of this treatment and the incidence of ischemic necrosis following embolization for acute GIH are poorly described. The purpose of this study was to evaluate the effectiveness and safety of "rescue" transcatheter superselective angioembolization (SSAE) for the treatment of hemodynamically unstable patients with GIH. METHODS: A 10-year retrospective review of all hemodynamically unstable patients (systolic blood pressure < 90 mm Hg and ongoing transfusion requirement) who underwent "rescue" SSAE for GIH after failed endoscopic management was performed. All patients with evidence of active contrast extravasation were included. Data were collected on demographics, comorbidities, clinical presentation, and type of intravascular angioembolic agent used. Outcomes included technical success (cessation of extravasation), clinical success (no rebleeding requiring intervention within 30 days), and incidence of ischemic complications. RESULTS: Ninety-eight patients underwent SSAE for GIH during the study period; 47 were excluded owing to lack of active contrast extravasation. Of the remaining 51 patients, 22 (43%) presented with a lower GIH and 29 (57%) with upper GIH. The majority underwent embolization with a permanent agent (71%), while the remaining patients received either a temporary agent (16%) or a combination (14%). The overall technical and clinical success rates were 98% and 71%, respectively. Of the 14 patients with technical success but clinical failure (rebleeding within 30 days) and the 1 patient with technical failure, 4 were managed successfully with reembolization, while 2 underwent successful endoscopic therapy, and 9 had surgical resections. Only one patient had an ischemic complication (small bowel necrosis) requiring resection. CONCLUSION: SSAE, with reembolization if necessary, is an effective rescue treatment modality for hemodynamically unstable patients with active GIH. Of the patients, 20% will fail SSAE and require additional intervention. Ischemic complications are extremely rare. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Fresh-frozen plasma resuscitation after traumatic brain injury and shock attenuates extracellular nucleosome levels and deoxyribonuclease 1 depletion.

INTRODUCTION: Traumatic brain injury and shock are among the leading causes of trauma-related mortality. We have previously shown that fresh-frozen plasma (FFP) resuscitation reduces the size of brain lesion and associated swelling compared with crystalloids. We hypothesized that this effect would be associated with an attenuation of circulating nucleosome levels, a biomarker of injury with cytotoxic potential, through reconstitution of circulating deoxyribonuclease-1 (DNAse1), an enzyme identified as critical in nucleosome clearance from the circulation. METHODS: Twelve swine underwent a protocol of traumatic brain injury followed by 40% volume-controlled hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for 2 hours before they were resuscitated with normal saline (NS) or FFP. Circulating levels of nucleosomes and DNAse1 were measured whereas extracellular nucleosomes were quantified on brain histology. Lesion size and brain swelling were also quantified. RESULTS: Nucleosome levels were significantly greater in the NS group 6 hours after resuscitation (0.32 mU vs 0.15 mU, P = .030) whereas DNAse1 levels were substantially greater in the FFP group (9.82 ng/mL vs 4.54 ng/mL, P = .010). Circulating nucleosomes levels correlated with lesion size (rho = 0.79, P = .002) as well as brain swelling (rho = 0.89, P < .001) whereas DNAse1 levels correlated with brain swelling (rho = -0.61, P = .036) but not lesion size (rho = -0.47, P = .124). Brain staining revealed nucleosome extracellularization in both groups, but this appeared more frequent in the NS-resuscitated animals. CONCLUSION: Our results show that resuscitation with FFP attenuates circulating nucleosome levels and prevents DNAse1 depletion. These factors may play a role in the neuroprotective effects observed during early resuscitation with FFP.

Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock.

BACKGROUND: Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether this effect was owing to metabolic modulation. METHODS: Yorkshire swine (n = 9) underwent a protocol of computer-controlled TBI and 40% hemorrhage and were resuscitated randomly with either fresh frozen plasma equal to the volume of shed blood (FFP; n = 4) or VPA (300 mg/kg) and FFP (FFP+VPA; n = 5). Hemodynamics, brain oxygenation, and blood glucose were monitored continuously for 6 hours after resuscitation. Cerebral microdialysis was used to measure glucose, lactate, pyruvate, glutamate, and glycerol levels at baseline, 1 and 2 hours post-shock, post-resuscitation (PR), and at 2, 4, and 6 hours PR. Brain samples from the injured side were then separated into mitochondrial and cytosolic fractions, and activity of pyruvate dehydrogenase complex (PDH) was measured using a dipstick assay kit. RESULTS: At baseline, there was no difference in brain lactate, pyruvate, glycerol, and glutamate concentrations between the groups. At all time points, there were no differences between the groups in brain oxygenation, cerebral perfusion pressure, or blood and brain glucose concentrations. After VPA infusion (PR time point), however, there was sustained decrease in lactate (0.91 ± 0.47 vs 2.54 ± 0.59 mmol/L; P < .01) and pyruvate (12.80 ± 4.89 vs 46.25 ± 9.22; P < .001) concentrations compared with the FFP alone group, implying superior glucose utilization for ATP production. There was also a decrease in concentrations of glutamate (6.64 ± 3.68 vs 42.25 ± 27.07 mmol/L; P = .02) and glycerol (19.20 ± 6.76 vs 69.75 ± 30.07 mmol/L; P = .01), in the FFP+VPA group, signifying lesser degree of excitotoxicity and brain damage, respectively. Brain PDH activity was greater in the mitochondrial fractions (5,984 ± 504 adjusted volume intensity [INT] × mm(2) vs 4,332 ± 1,055 INT × mm(2); P = .04) and lower in cytosolic fractions in the FFP+VPA group (1,597 ± 1,395 vs 4,026 ± 1,067 INT × mm(2); P = .03), indicating better mitochondrial membrane function and enhanced mitochondrial PDH retention. CONCLUSION: VPA treatment attenuates perturbation of post-traumatic cerebral metabolism by mitigating mitochondrial dysfunction, and decreases glutamate-mediated excitotoxic damage. These properties could explain its effectiveness in decreasing lesion size and post-traumatic cerebral edema.

Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock.

INTRODUCTION: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine model of combined TBI+HS. We have also shown separately that addition of valproic acid (VPA) to the resuscitation protocol attenuates inflammatory markers in the brain as well as the degree of TBI. The current study was performed to determine whether a combined FFP+VPA treatment strategy would exert a synergistic effect. METHODS: Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. TBI was created through a 20-mm craniotomy using a computer-controlled cortical impactor: 15-mm cylindrical tip impactor at 4 m/s velocity, 100 ms dwell time, and 12-mm penetration depth. The TBI was synchronized with the initiation of volume-controlled hemorrhage (40 ± 5% of total blood volume). After a 2-hour period of shock, animals were randomized to 1 of 3 resuscitation groups (n = 5 per group): (1) 0.9% saline (NS); (2) FFP; and (3) FFP and VPA 300 mg/kg (FFP+VPA). The resuscitative volume for FFP was equivalent to the shed blood, whereas NS was 3 times this volume. VPA treatment was started 1 hour after hemorrhage. Animals were monitored for 6 hours post-resuscitation. At this time the brains were harvested, sectioned into 5-mm slices, and stained with 2,3,5-triphenyltetrazolium chloride to quantify the lesion size (mm(3)) and brain swelling (percent change compared with the uninjured side). RESULTS: The combined TBI+HS model resulted in a highly reproducible brain injury. Lesion size and brain swelling (mean value ± standard error of the mean) in the FFP+VPA group (1,459 ± 218 mm(3) and 13 ± 1%, respectively) were less than the NS group (3,285 ± 131 mm(3) [P < .001] and 37 ± 2% [P < .001], respectively), and the FFP alone group (2,160 ± 203 mm(3) [P < .05] and 22 ± 1% [P < .001], respectively). CONCLUSION: In a large animal model of TBI+HS, early treatment with a combination of FFP and VPA decreases the size of brain lesion and the associated swelling.

Importance of intervening in the preconception period to impact pregnancy outcomes.

Preconception care that begins in adolescence and is provided before and between pregnancies has the potential to impact 136 million women who give birth each year and ensure that newborns receive the healthiest start possible. Providing simple interventions before pregnancy can prevent a significant proportion of maternal and neonatal mortality and morbidity. Interventions to promote adolescent health and prevent teenage pregnancies, encourage contraceptive use and appropriate birth spacing, optimize weight and micronutrient status, and screen for and manage chronic conditions have proven efficacy. These interventions must now be scaled up to maximize delivery. Women who receive preconception care are more likely to adopt healthy behaviors, and therefore have better pregnancy outcomes. Preconception care is particularly effective when men are involved and care is provided in the community setting. All healthcare providers can and should begin to provide preconception care to all adolescent girls, women and couples of reproductive age by asking them if they wish to become pregnant or are actively trying to prevent pregnancy.

Incidental findings in trauma patients: dedicated communication with the primary care physician ensures adequate follow-up.

BACKGROUND: Frequent use of computed tomography (CT) in trauma patients results in frequent detection of non-trauma-related incidental findings (IFs). Inpatient documentation and disclosure at discharge are infrequent, even when they are potentially serious. We aimed to not only identify the incidence of IFs but also to evaluate the effectiveness of an intervention to trigger follow-up. METHODS: In this before-after study, all trauma patients evaluated by the trauma surgery service who underwent CT were admitted for >24 h, had at least one IF requiring follow-up, and had a primary care physician (PCP) employed in our health care system were identified. The historical control period was from January 2006 to December 2008. The intervention period was from December 2011 to September 2012. Intervention consisted of notifying the PCP via email or postal letter. The outcome of interest-the rate of follow-up-was compared between both groups. RESULTS: During the historical period, 364 (20.5 %) of 1,774 eligible trauma patients had 434 IFs requiring follow-up. During the study period, 197 (26 %) of 692 trauma patients had 212 IFs requiring follow-up. Overall, 91 % of study patients with postdischarge PCP follow-up had documented follow-up of the IF. There was a significant improvement in the rate of follow-up in the study group compared to that of the control group (51 vs. 11 %; p < 0.0001). CONCLUSIONS: Detection of IFs is common in trauma patients. A dedicated effort of communicating the presence of an IF to the patient's PCP triggered a follow-up for 91 % of patients who saw their PCP after hospital discharge.

Born too soon: care before and between pregnancy to prevent preterm births: from evidence to action.

Providing care to adolescent girls and women before and between pregnancies improves their own health and wellbeing, as well as pregnancy and newborn outcomes, and can also reduce the rates of preterm birth. This paper has reviewed the evidence-based interventions and services for preventing preterm births, reported the findings from research priority exercise, and prescribed actions for taking this call further. Certain factors in the preconception period have been shown to increase the risk for prematurity and, therefore, preconception care services for all women of reproductive age should address these risk factors through preventing adolescent pregnancy, preventing unintended pregnancies, promoting optimal birth spacing, optimizing pre-pregnancy weight and nutritional status (including a folic acid-containing multivitamin supplement) and ensuring that all adolescent girls have received complete vaccination. Preconception care must also address risk factors that may be applicable to only some women. These include screening for and management of chronic diseases, especially diabetes; sexually-transmitted infections; tobacco and smoke exposure; mental health disorders, notably depression; and intimate partner violence. The approach to research in preconception care to prevent preterm births should include a cycle of development and delivery research that evaluates how best to scale up coverage of existing evidence-based interventions, epidemiologic research that assesses the impact of implementing these interventions and discovery science that better elucidates the complex causal pathway of preterm birth and helps to develop new screening and intervention tools. In addition to research, policy and financial investment is crucial to increasing opportunities to implement preconception care, and rates of prematurity should be included as a tracking indicator in global and national maternal child health assessments.

Knowledge, perceptions and myths regarding infertility among selected adult population in Pakistan: a cross-sectional study.

BACKGROUND: The reported prevalence of infertility in Pakistan is approximately 22% with 4% primary and 18% secondary infertility. Infertility is not only a medical but also a social problem in our society as cultural customs and perceived religious dictums may equate infertility with failure on a personal, interpersonal, or social level. It is imperative that people have adequate knowledge about infertility so couples can seek timely medical care and misconceptions can be rectified. We aim to assess the knowledge, perception and myths regarding infertility and suggest ways to improve it. METHODS: A cross-sectional survey was carried out by interviewing a sample of 447 adults who were accompanying the patients at two tertiary care hospitals in Karachi, Pakistan. They were interviewed one-on-one with the help of a pretested questionnaire drafted by the team after a thorough literature review and in consultation with infertility specialists. RESULTS: The correct knowledge of infertility was found to be limited amongst the participants. Only 25% correctly identified when infertility is pathological and only 46% knew about the fertile period in women's cycle. People are misinformed that use of IUCD (53%) and OCPs (61%) may cause infertility. Beliefs in evil forces and supernatural powers as a cause of infertility are still prevalent especially amongst people with lower level of education. Seeking alternative treatment for infertility remains a popular option for 28% of the participant as a primary preference and 75% as a secondary preference. IVF remains an unfamiliar (78%) and an unacceptable option (55%). CONCLUSIONS: Knowledge about infertility is limited in the population and a lot of misconceptions and myths are prevalent in the society. Alternative medicine is a popular option for seeking infertility treatment. The cultural and religious perspective about assisted reproductive technologies is unclear, which has resulted in its reduced acceptability.