Cost analysis of orthognathic surgery: outpatient care versus inpatient care.

With limited healthcare resources, it is important to provide the right level and form of care. The aim of this study was to determine whether selected single-jaw orthognathic surgery in outpatient care (OPC) generates lower healthcare costs than in inpatient care (IPC). The costs of surgically assisted rapid maxillary expansion (SARME), Le Fort I osteotomy (LFI), and bilateral sagittal split osteotomy (BSSO) were calculated for 165 patients, 107 treated in OPC and 58 in IPC. Additionally, costs for revisits, emergency visits, emergency phone calls, re-operations, and plate removal during the first 12 months postoperatively were recorded. The total mean costs of the different operations including revisits, emergency visits, and phone calls were 34.2-48.8% lower in OPC than in IPC at 12 months postoperatively. Operation costs were lower for LFI in OPC (P = 0.009) and for SARME in IPC (P = 0.007). Anaesthesia costs were lower for LFI (P < 0.001) and BSSO (P < 0.001) in OPC, and there were fewer revisits (P = 0.001) and lower costs (P = 0.002) after LFI in OPC compared to IPC. This study showed that selected single-jaw orthognathic surgeries in outpatient care are associated with lower healthcare costs compared to inpatient care.

Early and late preterm birth rates in participants adherent to randomly assigned high dose docosahexaenoic acid (DHA) supplementation in pregnancy.

BACKGROUND: Intention-to-treat analyses do not address adherence. Per protocol analyses treat nonadherence as a protocol deviation and assess if the intervention is effective if followed. OBJECTIVE: To determine the rate of early preterm birth (EPTB, <34 weeks gestation) and preterm birth (PTB, <37 weeks gestation) in participants who adhered to a randomly assigned docosahexaenoic acid (DHA) dose of 1000 mg/day. STUDY DESIGN: Eleven hundred women with a singleton pregnancy were enrolled before 20-weeks' gestation, provided a capsule with 200 mg/day DHA and randomly assigned to two additional capsules containing a placebo or 800 mg of DHA. In the Bayesian Adaptive Design, new randomization schedules were determined at prespecified intervals. In each randomization, the group with the most EPTB was assigned fewer participants than the other group. Adherence was defined a priori as a postpartum red blood cell phospholipid DHA (RBC-PL-DHA) ≥5.5%.and post hoc as ≥8.0% RBC-PL-DHA, the latter after examination of postpartum RBC-PL-DHA. Bayesian mixture models were fitted for gestational age and dichotomized for EPTB and PTB as a function of baseline RBC-PL-DHA and dose-adherence. Bayesian hierarchical models were also fitted for EPTB by dose adherence and quartiles of baseline RBC-PL-DHA. RESULTS: Adherence to the high dose using both RBC-PL-DHA cut points resulted in less EPTB compared to 200 mg [Bayesian posterior probability (pp) = 0.93 and 0.92, respectively]. For participants in the two lowest quartiles of baseline DHA status, adherence to the higher dose resulted in lower EPTB (≥5.5% RBC-PL-DHA, quartiles 1 and 2, pp = 0.95 and 0.96; ≥8% RBC-PL-DHA, quartiles 1 and 2, pp = 0.94 and 0.95). Using the Bayesian model, EPTB was reduced by 65%, from 3.45% to 1.2%, using both cut points. Adherence also reduced PTB before 35, 36 and 37 weeks using both cut points (pp ≥ 0.95). In general, performance of the nonadherent subgroup mirrored that of participants assigned to 200 mg. CONCLUSION: Adherence to high dose DHA reduced EPTB and PTB. The largest effect of adherence on reducing EPTB was observed in women with low baseline DHA levels. CLINICALTRIALS: gov (NCT02626299).

Patient safety with orthognathic surgery in an outpatient setting.

Orthognathic surgery is traditionally performed in inpatient care. The question is whether patient safety is maintained when orthognathic surgery is performed in outpatient care. This retrospective cohort study was conducted to investigate patient safety in selected single-jaw orthognathic surgeries performed in outpatient care compared to inpatient care. Postoperative infection, postoperative bleeding, postoperative pain, plate removal, and re-operation, as well as emergency visits/phone calls and postoperative admission during the first 12 months after surgery were recorded. Predictor variables were sex, age, smoking, general disease, antibiotics, operation type, and operation time. Of the 165 patients included, 58 were treated in inpatient care and 107 in outpatient care. No significant difference was found between the groups regarding postoperative bleeding, pain, plate removal, re-operation, or emergency visits/phone calls. Ninety-four percent of outpatients (n = 101) were able to leave the hospital on the day of surgery as planned. There was an increased risk of postoperative infection in the outpatient care group (odds ratio 2.46, P = 0.049). Selected single-jaw orthognathic surgery can be performed in the outpatient setting, with maintained patient safety. The reason for the increased risk of postoperative infection among patients operated in outpatient care should be investigated in further studies.

Difficult situations and moral questions raised during moral case deliberations in Swedish childhood cancer care - A qualitative nationwide study.

PURPOSE: To describe performed moral case deliberations and present a nationwide study of difficult situations and moral questions raised by healthcare professionals during moral case deliberations in Swedish childhood cancer care. METHODS: Written reports (n = 72) about difficult situations and moral questions were completed by healthcare professionals, trained as facilitators, who implemented moral case deliberations at all paediatric oncology centres in Sweden. A qualitative systematic text condensation was used for data analysis. RESULTS: A pattern of biopsychosocial factors was found in the difficult situations, including medical, psycho-social, and religious/cultural information. Three different themes of moral questions emerged. The first, "What is the limit of healthcare professionals' responsibilities?", included whether, and to what degree, healthcare professionals should depart from professional values, and whether/when to interfere with parents' choices in care. The second theme, "Who has a mandate to decide on care?", covered conflicting perspectives on care related to decision making. The third theme, "What is the right care action to take?", concerned the best interest of the child and moral questions about whether the chosen care action would promote a better or worse outcome. CONCLUSIONS: This study contributes to increased understanding of difficult situations and moral questions raised during moral case deliberations in Swedish childhood cancer care. Biopsychosocial factors are important to take into account in order to achieve a holistic view of the situation. Although several moral questions concerned medical treatment and life and death, others were related to everyday clinical practice and the differing perspectives of children, parents, and healthcare professionals.

Early pregnancy prediction of spontaneous preterm birth before 32 completed weeks of pregnancy using plasma RNA: transcriptome discovery and initial validation of an RNA panel of markers.

OBJECTIVE: To compare the second-trimester plasma cell-free (PCF) transcriptome of women who delivered at term with that of women with spontaneous preterm birth (sPTB) at or before 32 weeks of gestation and identify/validate PCF RNA markers present by 16 weeks of gestation. DESIGN: Prospective case-control study. SETTING: Academic tertiary care centre. POPULATION: Pregnant women with known outcomes prospectively sampled. METHODS: PCF RNAs extracted from women at 22-24 weeks of gestation (five sPTB up to 32 weeks and five at term) were hybridised to gene expression arrays. Differentially regulated RNAs for sPTB up to 32 weeks were initially selected based on P value compared with control (P < 0.01) and fold change (≥1.5×). Potential markers were then reordered by narrowness of distribution. Final marker selection was made by searching the Metacore™ database to determine whether the PCF RNAs interacted with a reported set of myometrial Preterm Initiator genes. RNAs were confirmed by quantitative reverse transcription polymerase chain reaction and tested in a second group of 40 women: 20 with sPTB up to 32 weeks (mean gestation 26.5 weeks, standard deviation ±2.6 weeks), 20 with spontaneous term delivery (40.1 ± 0.9 weeks) sampled at 16-19+5  weeks of gestation. MAIN OUTCOME MEASURE: Identification of PCF RNAs predictive of sPTB up to 32 weeks. RESULTS: Two hundred and ninety-seven PCR RNAs were differentially expressed in sPTB up to 32 weeks of gestation. Further selection retained 99 RNAs (86 mRNAs and 13 microRNAs) and five of these interacted in silica with seven Preterm Initiator genes. Four of five RNAs were confirmed and tested on the validation group. The expression of each confirmed PCF RNA was significantly higher in sPTB up to 32 weeks of gestation. In vitro study of the four mRNAs revealed higher expression in placentas of women with sPTB up to 32 weeks and the potential to interfere with myometrial quiescence. CONCLUSIONS: The PCF RNA markers are highly associated with sPTB up to 32 weeks by 16 weeks of gestation. TWEETABLE ABSTRACT: Women destined for spontaneous preterm birth can be identified by 16 weeks of gestation with a panel of maternal plasma RNAs.

Difficult to treat: are there organism-dependent differences and overall risk factors in success rates for two-stage knee revision?

OBJECTIVES: Failure after two-stage procedure for periprosthetic joint infection (PJI) is a rare, but devastating complication. Some authors assume a correlation of underlying organisms and recurrence rate. Methicillin-resistant Staphylococci (MRS) and other organisms (quinolone-resistant Gram-negative bacteria, rifampicin-resistant Staphylococcus, Enterococcus, and Candida) are meant to be "difficult to treat" (DTT) with an inferior outcome for two-stage revision. In addition to the type of bacteria, some more risk factors seem to be present. The aim of this study was (1) to detect a difference of reinfection rates between reinfection-causing groups of bacteria ["difficult to treat" (DTT), "easy to treat" (ETT) and methicillin-resistant staphylococci (MRS)] after a two-stage procedure, and (2) find overall risk factors for reinfection in a standardized long (spacer insertion for at least 6 weeks) two-stage procedure for periprosthetic knee infection. METHODS: One hundred and thirty-seven two-stage revisions for periprosthetic knee infection were performed at one tertiary referral center. Finally, 96 patients could be included for analyses. Possible risk factors (comorbidities, prior surgery, etc.) and the types of organisms were documented. Quinolone-resistant Gram-negative bacteria, rifampicin-resistant Staphylococcus, Enterococcus, and Candida were classified as "difficult to treat" (DTT). Methicillin-resistant Staphylococci were summarized as "MRS", all other organism are summarized as "easy to treat" (ETT). Statistical analyses included univariate analysis (t test, Fisher's exact test, Chi square test) and logistic regression analysis. RESULTS: There were no statistical significant differences in recurrent infection rates between organism groups (DTT vs. ETT, p = 0.674; DTT vs. MRS, p = 0.705; ETT vs. MRS, p = 0.537). Risk factors seem to be "need of revision after first stage" (p = 0.019, OR 5.62) or completed second stage (p = 0.000, OR 29.07), numbers of surgeries (p = 0.028) and alcohol abuse (p = 0.019, OR 5.62). CONCLUSIONS: Revision needed during or after a two-stage exchange, numbers of surgeries and alcohol abuse are risk factors for recurrence, a different recurrence rates between organism-groups cannot be shown. The absence of significant differences in recurrence rates points to the importance of the individuality of each periprosthetic infection case: a reduction of necessary surgeries (with a thorough debridement, appropriate antibiotic addition to spacers) and the control of comorbidities (alcohol abuse) appear to be essential components of a two-stage exchange.

Predictive factors in temporomandibular joint arthroscopy: a prospective cohort short-term outcome study.

Improving the outcomes of surgical treatment of the temporomandibular joint (TMJ) is beneficial from a patient and health-economy perspective. Optimizing conditions for a successful result can be reached using validated, strict diagnostic criteria and by identifying patient-specific factors predicting the outcome. The aim of this study was to investigate possible predictive factors in TMJ arthroscopy. A prospective cohort study including 93 patients undergoing arthroscopy was conducted. The outcome was graded as successful (53%, n=49), good (25%, n=23), intermediate (20%, n=19), or deteriorated (2%, n=2) using a predefined set of objective and subjective outcome measures. The outcome was correlated with preoperative and perioperative variables and the diagnosis. Preoperative bilateral masticatory muscle tenderness on palpation was the only variable significantly correlated with a negative outcome in the adjusted regression analysis (odds ratio (OR) 2.56, P=0.048). Low age (OR 1.03, P=0.05) and bilateral joint surgery/operated side (OR 0.24, P=0.05) were found to correlate with an unsuccessful outcome in the unadjusted analysis. Eighty-nine percent of the patients with osteoarthritis benefited from arthroscopy, while corresponding figures were 80% for disc displacement without reduction and 64% for chronic inflammatory arthritis. Preoperative bilateral masticatory tenderness might be a useful predictive factor suggesting the consideration of revised non-invasive therapy before surgery.

Outcome of Irrigation and Debridement after Failed Two-Stage Reimplantation for Periprosthetic Joint Infection.

INTRODUCTION: Two-stage revision is the gold standard for the treatment of deep implant infection after knee or hip arthroplasty. Irrigation and debridement may be a treatment option for failed 2-stage revisions in cases where a reinfection occurs within 30 days or the symptoms exist not longer than 3 weeks and is appealing because of its low morbidity. We determined the incidence of recurrent infections following irrigation and debridement for failed two-stage revision hip and knee arthroplasty. METHODS: We performed a single center retrospective review of periprosthetic hip and knee infections treated with a two-stage procedure from 2002 to 2010. All patients that subsequently underwent irrigation and debridement for a subsequent infection were selected for the current study. RESULTS: 440 two-stage revisions were performed between 2002 and 2010. Fifty-one two-stage revisions failed (11.6%). Nineteen failed two-stage revisions were treated with irrigation and debridement; 12 (63.2%) patients remained free of infection at follow-up (mean follow-up: 39 months; range, 24-90 months), infection persisted in 6 patients (31.6%), and 1 patient died (5.3%). CONCLUSIONS: Success rates of irrigation and debridement for failed two-stage procedures are similar to the success rates of irrigation and debridement in primary implant infections. According to the current paper, irrigation and debridement are an acceptable treatment for acute reinfections after failed two-stage revision if performed within the first 30 postoperative days after failed two-stage procedure or if symptoms are present for less than 3 weeks in the presence of a susceptible organism.

Multi-professional training for obstetric emergencies in a U.S. hospital over a 7-year interval: an observational study.

OBJECTIVE: Birth is less safe than it can be. We adapted the UK-developed PROMPT (PRactical Obstetric Multi-Professional Training) course to local practices and initiated annual training. STUDY DESIGN: This observational study used quality assurance data from University of Kansas Hospital 2 years before and 7 years after intervention encompassing 14,309 consecutive deliveries from January 2006 through December 2014. An events/trials approach was applied to changes in proportions over time. RESULT: PROMPT was associated with progressive decreases in rates (P<0.05) of brachial plexus injury and umbilical artery pH <7.00 exclusive of catastrophic events. Reduced rates (P<0.05) of cesarean section, episiotomy and higher perception of nurse/physician communication were documented. Hypoxic ischemic encephalopathy (HIE) rates declined progressively by >50% (P=NS). These improvements occurred despite younger faculty and higher rates of complicated pregnancies (P<0.05). Estimated health-care costs avoided exceeded annual training costs. CONCLUSION: Local annual multi-professional training as provided by PROMPT was temporally associated with improved obstetric outcomes.

Complications associated with 133 static, antibiotic-laden spacers after TKA.

PURPOSE: Periprosthetic infection after total knee arthroplasty (TKA) is a devastating complication, with a two-stage revision currently the 'gold standard' treatment for chronic infections. There is, however, a lack of information about mechanical complications during this treatment. The purpose of this study was to determine: (1) the rate and type of mechanical complications encountered during a two-stage exchange revision for periprosthetic infection of the knee and (2) possible factors of influence. METHODS: Between 2000 and 2011, 133 patients received an antibiotic-laden cement spacer as part of a two-stage protocol. The overall frequency and types of complication were recorded (fissure/fracture of the tibia or femur, spacer fracture, subluxation of the patella, peroneus affection, wound healing disorder and mobilization under anaesthesia based on a constricted ROM). Also analysed were potential influencing factors (BMI, ASA classification, length of the interval with the enclosed spacer, revision needed after explantation, revision needed after reimplantation, complications after primary TKA, service life of the primary prosthesis) in terms of the overall outcome (possibility of reimplantation, complications during the two-stage protocol). RESULTS: The mean age at the time of the first stage operation was 70.1 ± 9.9 years. Overall, 20 of 133 patients suffered one of the complications mentioned above (15 %). Fracture/fissure of the tibia occurred in nine cases (6.8 %) and fracture/fissure of the femur in three (2.3 %). There were also three mobilizations under anaesthesia after TKA reimplantation, two affections of the peroneus nerve, one spacer fracture, one subluxation of the patella and one wound healing disorder. The influencing factors on the overall outcome were revision after reimplantation (reinfection, p = 0.002), revision after explantation (reinfection, p = 0.044), prior aseptic revision after primary TKA (reimplantation, p = 0.019), and prior two-stage revision (reimplantation, p = 0.002). CONCLUSION: A two-stage revision arthroplasty using a static cement spacer is an effective therapy for infected TKAs. The complication rate of 15 % (including restricted ROM after reimplantation) is acceptable. Influencing factors (revision needed after reimplantation, revision needed after explantation) can be demonstrated and should be avoided during the two-stage protocol.

Osteochondroma of the glenoid fossa--report of two cases with sudden onset of symptoms.

Osteochondroma of the temporomandibular joint is a rare condition that most frequently affects the mandibular condyle. Fixed osteochondroma originating from the glenoid fossa is extremely rare and a literature search identified only two reported cases. The cases of two additional patients in whom osteochondroma developed in the posterior part of the glenoid fossa leading to the sudden onset of chin deviation and malocclusion are reported herein. We conclude that osteochondroma of the glenoid fossa is a slow growing benign tumour with typical clinical and radiological features. It requires surgical treatment, comprising resection of the tumour. Recurrence appears unlikely.

Interferon stimulated genes, CXCR4 and immune cell responses in peripheral blood mononuclear cells infected with bovine viral diarrhea virus.

Non-cytopathic bovine viral diarrhea virus (ncpBVDV) induces immune responses mediated by chemokines and interferon (IFN) stimulated genes (ISGs). Cultured bovine peripheral blood mononuclear cells (PBMC) from ncpBVDV-naïve cattle were used herein to demonstrate that BVDV infection modulates chemokine receptor 4 (CXCR4), CXCL12, IFN-I, ISGs and selected immune cell marker (CD4, CD8, CD14) mRNAs, and that these acute responses to viral infection are reflected in PBMC cultured with serum from heifers carrying fetuses persistently infected (PI) with ncpBVDV. Infection of PBMC with ncpBVDV increased IFN-ß, ISG15, RIG-I, CXCR4, CXCL12, and CD8 mRNA concentrations after 32 h. Culture of PBMC with uterine vein serum from acutely infected heifers, inoculated with ncpBVDV during early gestation to generate PI fetuses, also increased the concentration of CXCR4, RIG-I and ISG15 mRNAs. In vitro PBMC treatment with ncpBVDV or uterine vein serum from acutely infected pregnant heifers activates chemokine, ISG and immune cell responses.

Bovine viral diarrhea virus cyclically impairs long bone trabecular modeling in experimental persistently infected fetuses.

Persistent infection (PI) with bovine viral diarrhea virus (BVDV) has been associated with osteopetrosis and other long bone lesions, most commonly characterized as transverse zones of unmodeled metaphyseal trabeculae in fetuses and calves. This study was undertaken to characterize the morphogenesis of fetal long bone lesions. Forty-six BVDV-naïve pregnant Hereford heifers of approximately 18 months of age were inoculated with noncytopathic BVDV type 2 containing media or media alone on day 75 of gestation to produce PI and control fetuses, respectively, which were collected via cesarean section on days 82, 89, 97, 192, and 245 of gestation. Radiographic and histomorphometric abnormalities were first detected on day 192, at which age PI fetal long bone metaphyses contained focal densities (4 of 7 fetuses) and multiple alternating transverse radiodense bands (3 of 7 fetuses). Day 245 fetuses were similarly affected. Histomorphometric analysis of proximal tibial metaphyses from day 192 fetuses revealed transverse zones with increased calcified cartilage core (Cg.V/BV, %) and trabecular bone (BV/TV, %) volumes in regions corresponding to radiodense bands (P < .05). Numbers of tartrate resistant acid phosphatase positive osteoclasts (N.Oc/BS, #/mm(2)) and bone perimeter occupied (Oc.S/BS, %) were both decreased (P < .05). Mineralizing surface (MS/BS, %), a measure of tissue level bone formation activity, was reduced in PI fetuses (P < .05). It is concluded that PI with BVDV induces cyclic abnormal trabecular modeling, which is secondary to reduced numbers of osteoclasts. The factors responsible for these temporal changes are unknown but may be related to the time required for osteoclast differentiation from precursor cells.

The active components of effective training in obstetric emergencies.

Confidential enquiries into poor perinatal outcomes have identified deficiencies in team working as a common factor and have recommended team training in the management of obstetric emergencies. Isolated aviation-based team training programmes have not been associated with improved perinatal outcomes when applied to labour ward settings, whereas obstetric-specific training interventions with integrated teamwork have been associated with clinical improvements. This commentary reviews obstetric emergency training programmes from hospitals that have demonstrated improved outcomes to determine the active components of effective training. The common features identified were: institution-level incentives to train; multi-professional training of all staff in their units; teamwork training integrated with clinical teaching and use of high fidelity simulation models. Local training also appeared to facilitate self-directed infrastructural change.

Prevalence of viral DNA in amniotic fluid of low-risk pregnancies in the second trimester.

AIM: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnancies is not established. The purpose of this study was to determine this prevalence in asymptomatic patients. METHODS: This was a prospective observational study of patients at low risk for viral infection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesis was analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV). RESULTS: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen (n = 164, 23.9%), elevated maternal serum alpha-fetoprotein (n = 20, 2.9%), previous aneuploidy (n = 16, 2.3%) and family history of inheritable disease (n = 14, 2.1%). Forty-four (6.4%) amniotic fluid samples were positive for viral genome. A single genome was amplified in 41 samples (93%). In three samples, two viral genomes were identified. Adenovirus was most frequently identified (37/44), followed by CMV (5/44), EBV (2/44), enterovirus (2/44) and RSV (1/44). Parvovirus and HSV were not identified. There was a bimodal seasonal variation in prevalence, with the highest prevalence during the summer and late winter. CONCLUSION: Viral genome is commonly found in amniotic fluid with a sonographically normal fetus, and the prevalence follows a seasonal pattern. The mechanism, significance and effects of this asymptomatic viral presence require further study.

Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses.

BACKGROUND: Our aim was to test the hypothesis that qualitative ductus venosus and umbilical venous Doppler analysis improves prediction of critical perinatal outcomes in preterm growth-restricted fetuses with abnormal placental function. METHODS: Patients with suspected intrauterine growth restriction (IUGR) underwent uniform fetal assessment including umbilical artery (UA), ductus venosus (DV) and umbilical vein (UV) Doppler. Absent or reversed UA end-diastolic velocity (UA-AREDV), absence or reversal of atrial systolic blood flow velocity in the DV (DV-RAV) and pulsatile flow in the umbilical vein (P-UV) were examined for their efficacy to predict critical outcomes (stillbirth, neonatal death, perinatal death, acidemia and birth asphyxia) before 37 weeks' gestation. RESULTS: Seventeen (7.6%) stillbirths and 16 (7.1%) neonatal deaths were observed among 224 IUGR fetuses. Forty-one neonates were acidemic (19.8%) and seven (3.1%) had birth asphyxia. Logistic regression showed that UA-AREDV had the strongest association with perinatal mortality (R(2) = 0.49, P < 0.001), stillbirth (R(2) = 0.48, P < 0.001) and acidemia (R(2) = 0.22, P = 0.002) while neonatal death was most strongly related to DV-RAV and P-UV (R(2) = 0.33, P = 0.007). UA waveform analysis offered the highest sensitivity and negative predictive value and DV-RAV and P-UV had the best specificity and positive predictive values for outcome prediction. Overall, DV-RAV or P-UV offered the best prediction of acidemia and neonatal and perinatal death irrespective of the UA waveform. In fetuses with UA-AREDV, prediction of asphyxia and stillbirth was significantly enhanced by venous Doppler. CONCLUSION: Prediction of critical perinatal outcomes is improved when venous and umbilical artery qualitative waveform analysis is combined. The incorporation of venous Doppler into fetal surveillance is therefore strongly suggested for all preterm IUGR fetuses.

Pregnancy and estradiol decrease GTPase activity in the guinea pig uterine artery.

The mechanisms by which pregnancy redistributes cardiac output in an organ-specific manner are poorly understood. We propose that it is consequential to estrogen-mediated alterations in G protein-mediated signal transduction. Aortas and uterine (UAs) and mesenteric arteries (MAs) were obtained from late-pregnant, nonpregnant, or ovariectomized guinea pigs chronically treated with 17beta-estradiol. High-affinity GTPase activity was assayed enzymatically. The cGMP generated in response to the endothelium-dependent agonist ACh was measured in UAs incubated with or without cholera toxin (CTX, which inhibits G(s)alpha). Pregnancy significantly decreased UA but not aorta or MA GTPase activity. 17beta-Estradiol decreased UA GTPase activity compared with untreated ovariectomized animals. ACh increased cGMP in pregnant but not nonpregnant UAs. Pretreatment of nonpregnant UAs with CTX increased ACh-induced cGMP levels similar to pregnancy. Thus pregnancy and estradiol decrease the GTPase activity of a CTX-sensitive G protein in UAs, increasing receptor-dependent cGMP release. This alteration in receptor-mediated G protein coupling in UAs may contribute to the characteristic cardiovascular adaptation to pregnancy.

Leveraging healthcare for the greater good: lessons learned from the National Centers of Excellence in Women's Health.

The creation of the National Centers of Excellence in Women's Health (CoE) program in 1996 by the Office on Women's Health, Department of Health and Human Services, included the stipulation that each institution awarded a CoE contribute at least a 25% match for the federal funds. Even the combination of these two sources of monies was insufficient for each CoE to accomplish its goals, however, so leveraging funds became necessary for each CoE to function effectively. The forms of leveraging varied from CoE to CoE, in part as a result of the institutional environment and the unique possibilities each permitted and in part as a result of the creativity of the leaders of the CoEs. This paper describes the concepts and some applications of leveraging in the setting of the CoEs, which might be applicable to other settings as well.

Women's health centers and minority women: addressing barriers to care. The National Centers of Excellence in Women's Health.

New models of care delivery have been developed to better coordinate and integrate healthcare for women. In the United States, one of the challenges is to incorporate the needs of racial and ethnic minority populations into these newer care paradigms. This paper begins with a brief historical review of the experience of racial and ethnic minorities in the American healthcare system to provide a context for discussing barriers and limitations of more traditional models of women's healthcare. Specific approaches used by National Centers of Excellence in Women's Health are presented as examples of strategies that may be implemented by other communities to address these barriers.