Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Maternal anaemia and maternal, fetal, and neonatal outcomes in a prospective cohort study in India and Pakistan.

OBJECTIVE: To describe the association of maternal anaemia with maternal, fetal, and neonatal outcomes. DESIGN: Prospective cohort study. SETTING: Rural India and Pakistan. POPULATION: Pregnant women residing in the study catchment area. METHODS: We performed an analysis of a prospective pregnancy registry in which haemoglobin is commonly obtained as well as maternal, fetal, and neonatal outcomes for 42 days post-delivery. Women 40 years or older who delivered before 20 weeks or had a haemoglobin level of <3.0 g/dl were excluded. Our primary exposure was maternal anaemia, which was categorised in keeping with World Health Organization criteria based on a normal (≥11 g/dl), mild (>10-10.9 g/dl), moderate (7-9.9 g/dl) or severe (<7 g/dl). haemoglobin level. The primary maternal outcome was maternal death, the primary fetal outcome was stillbirth, and the primary neonatal outcome was neonatal mortality <28 days. RESULTS: A total of 92 247 deliveries and 93 107 infants were included, of which 87.8% were born to mothers who were anaemic (mild 37.9%, moderate 49.1%, and severe 0.7%). Maternal mortality (number per 100 000) was not associated with anaemia: normal 124, mild 106, moderate 135, and severe 325 (P = 0.64). Fetal and neonatal mortality was associated with severe anaemia: stillbirth rate (n/1000)-normal 27.7, mild 25.8, moderate 30.1, and severe 90.9; P < 0.0001; 28-day neonatal mortality (n/1000)-normal 24.7, mild 22.9, moderate 28.1, and severe 72.6 (P < 0.0001). Severe maternal anaemia was also associated with low birthweight (<2500 and <1500 g), preterm birth, and postpartum haemorrhage. CONCLUSION: Severe maternal anaemia is associated with higher risks of poor maternal, fetal, and neonatal outcomes but other degrees of anaemia are not. Interventions directed at preventing severe anaemia in pregnant women should be considered. TWEETABLE ABSTRACT: Severe maternal anaemia is associated with adverse fetal and neonatal outcomes in low/middle-income countries.

Clindamycin to reduce preterm birth in a low resource setting: a randomised placebo-controlled clinical trial.

OBJECTIVE: To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH ≥5.0. DESIGN: Randomised double-blind placebo-controlled trial. SETTING: Rural southern India. POPULATION: Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks. METHODS: Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (≥5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks. RESULTS: Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of<2500 g, <1500 g, miscarriage, stillbirth or neonatal death. CONCLUSION: In this setting, oral clindamycin did not decrease PTB among women with vaginal pH ≥5.0. TWEETABLE ABSTRACT: Oral clindamycin between 13+0/7 and 20+6/7 weeks does not prevent preterm birth in women with a vaginal pH ≥5.0.

Nonoperative management of blunt splenic injury: what is new?

The majority of splenic injuries are currently managed nonoperatively. The primary indication for operative management of blunt splenic injury is hemodynamic instability. Findings which correlate with failure of nonoperative management include grade IV or V splenic injury, high Injury Severity Scores, or active extravasation. The role of angiograph/embolization is becoming better defined, appropriate in the patient with pseudoaneurysm or active extravasation or the stable patient with grade IV or V splenic injury.

Estrogen therapy in women undergoing coronary artery bypass grafting: effect on surgical complications.

OBJECTIVE: To determine whether estrogen therapy at the time of coronary artery bypass grafting affects postoperative complications. METHODS: Consecutive postmenopausal women who had coronary artery bypass grafting between 1992 and 1997 were identified and their medical records were reviewed. Outcome measures included mortality, perioperative cardiac morbidity, and early and late postoperative complications. RESULTS: Estrogen therapy was noted in 13.9% of 734 women. Those using estrogen replacement were younger (63.9 +/- 0.27 versus 68.8 +/- 0.64 years) and had higher ejection fractions (2.8 +/- 0.11 versus 3.1 +/- 0.04) and fewer vessels bypassed. Mortality rates were 2.9% for estrogen users and 7.4% for nonusers (odds ratio [OR] 0.38; confidence interval [CI] 0.07, 1.21). Perioperative cardiac morbidity rates were 5.8% for estrogen users and 11% for nonusers (OR 0.52; CI 0.23, 1.7). Early complication rates were 0. 98% for estrogen users and 1.11% for nonusers. Late inpatient complications were noted in 6.8% of treated women and 14.8% of those untreated (OR 0.42; CI 0.16, 0.96). Stepwise logistic regression confirmed age, New York Heart Association angina classification, and ejection fraction as significant variables for mortality, perioperative cardiac morbidity, and late complications. Estrogen therapy did not influence mortality, perioperative cardiac morbidity, or early or late complications. CONCLUSION: Age, ejection fraction, and New York Heart Association angina classification predicted mortality, perioperative cardiac morbidity, and late complications. Estrogen therapy at the time of admission for coronary artery bypass grafting did not influence surgical mortality, perioperative cardiac morbidity, or early or late complications.

Influence of specialty on pathology resource use in evaluation of cervical dysplasia.

OBJECTIVE: Colposcopy is performed by different providers, including nurse practitioners, family physicians, and gynecologists. The training and experience of these providers vary. The fiscal impact of provider type is unknown. This study evaluates pathology resource use by gynecologists and nongynecologists at the time of colposcopy. METHODS: A retrospective cohort study was performed. Data were collected by review of pathology reports and records of all patients with cervical dysplasia treated with cervical excision by loop electrosurgical excision procedure or cold knife conization at our institution between January 1, 1996, and December 31, 1997. Data were analyzed according to type of provider performing the colposcopy before the cervical excision. RESULTS: Gynecologists obtained a total of 190 biopsy specimens in 127 patients, with a mean number of 1.5 +/- 0.75 per patient and a median of 1. Nongynecologists took a total of 148 biopsy specimens in 44 patients, with a mean of 3.4 +/- 1.14 per patient and a median of 3 (P < .001). These differences persisted irrespective of presenting cytology. Nongynecologists were more likely to do endocervical curettage than gynecologists (95% compared with 82%, respectively, P < .001). Cervical dysplasia was diagnosed equally well, even though fewer biopsies were taken by gynecologists. CONCLUSION: Both groups of providers were equally capable of identifying dysplastic lesions. Despite equivalent diagnostic accuracy, nongynecologists used two to three times more pathology resources. If this pattern of use of resources exists at other clinical sites, patients with cervical dysplasia and payers would be better served by gynecologic rather than nongynecologic care.

Predictive value for infection of febrile morbidity after vaginal surgery.

OBJECTIVE: To determine the screening value of febrile morbidity for detecting infections after vaginal surgery. METHODS: A cohort of 431 consecutive women had vaginal surgery at the M. S. Hershey Medical Center from September 1988 through June 1995. Outcomes of febrile morbidity and infection were analyzed. RESULTS: Fifty-four of 431 patients (12.5%) had febrile morbidity. Thirty-five infections (8.1%) were identified, of which only 13 were accompanied by febrile morbidity. Forty-one patients (9.5%) had unexplained fevers. The sensitivity of febrile morbidity for postoperative infection was 40%, specificity was 98%, positive predictive value was 26%, and negative predictive value was 94%. Stepwise logistic regression found blood loss (odds ratio 1.001/mL; confidence interval 1.0001-1.0035), uterine weight (0.987/g; 0.976-0.999), and parity (1.570; 1.146-2.050) as significant independent variables for developing fever. Patient weight (0.984/lb; 0.971-0.998) and type of procedure (2.16; 2.12-6.38) were confirmed as significant independent variables for postsurgical infections. CONCLUSION: Febrile morbidity had limited value as a screening test for postoperative infection, with poor sensitivity and positive predictive value after vaginal surgery.

Arteriovenous malformations of the uterus: an uncommon cause of vaginal bleeding.

Arteriovenous malformations (AVM) are rare entities in gynecology, with only 73 cases reported in the literature. Most commonly they present with vaginal hemorrhage, but other presentations such as congestive heart failure, postmenopausal bleeding, and an asymptomatic mass have been described. These lesions may be congenital or acquired. Acquired lesions are believed to follow trauma or may arise after choriocarcinoma or other gynecologic malignancies. Diagnosis can rapidly be made with color flow Doppler ultrasound or angiography. Additionally, they have been detected using hysteroscopy, hysterosalpingogram, and computerized tomography. Acute management consists of hemodynamic stabilization and possibly placement of a Foley bulb in the uterus or methylergonovine injection. Ultimate treatment depends on the patients desire for fertility. Embolization therapy is variably successful and may allow the preservation of reproductive capacity. To date, five pregnancies after embolization have been reported with varying outcomes. If pregnancy is not desired or embolization fails, hysterectomy remains the treatment of choice.

Synthesis of methyl alpha- and beta-D-xylopyranoside-5-18O.

Methyl alpha- and beta-D-xylopyranoside-5-18O (5 and 6) were prepared by way of oxygen exchange between 18O-water and the periodate-oxidation product (1) obtained from 1,2-O-isopropylidene-alpha-D-glucofuranose. The isotopic enrichment of 5 and 6 was determined by hydrolysis of each to D-xylose-5-18O (3), conversion of the sugar into 1,2,3,4-tetrakis-O-(tert-butyldimethylsilyl)-beta-D-xylopyranose-5-18O (7), and determination of the 18O content of the latter by use of a quadrupole, mass spectrometer.

Regulatory approaches for controlling pesticide residues in food animals.

Pesticide use is vital to the production of an economical, high-quality food supply throughout the world. The regulatory system in the United States is designed to prevent the entry of unacceptable residues into the food supply. To address the complexities associated with pesticide use, the regulatory apparatus is composed of several federal and numerous state agencies. Based on monitoring results, it appears that most pesticides are being used in the appropriate manner and that thresholds for pesticides, deemed to be adequate to protect human health, are seldom exceeded. With our increasing knowledge of the public health and ecologic threats posed by pesticide residues, our approach to regulating pesticides will continue to evolve.

Labor analgesia for patients with preterm premature rupture of membranes.

OBJECTIVE: Cervical examination is relatively contraindicated in women with preterm premature rupture of membranes (PPROM), limiting our ability to determine the onset of labor by traditional definition (contractions with cervical change). We sought to determine whether two maternal requests for analgesia within 3 h predicted delivery within 24 h to allow appropriate epidural placement. STUDY DESIGN: We performed a retrospective chart review of all patients with PPROM for a period of 18 months. Our primary outcome was the percentage of women with PPROM (<34 weeks) who delivered within 24 h from the second analgesia request. RESULT: Among women with PPROM, 63% delivered within 24 h from their second request for analgesia and 98% delivered within 48 h. CONCLUSION: Two medication requests within 3 h for regular, painful contractions can be used as an indicator of onset of labor in women with PPROM to allow for labor analgesia.

Endogenous occurrence of some anabolic steroids in swine matrices.

Following findings of 17beta-19-nortestosterone (150-200 microg kg(-1)) in pigs of unspecified gender imported into the European Union, a study to determine steroid and hormone levels in swine from six age/gender categories (uncastrated 'old' boars, cryptorchids, one intersex, barrows, gilts and sows) was initiated. Indeed, for some hormones there has been a discussion about their being endo- or exogenous. Tissue and urine samples from swine from each of the six categories were obtained in Belgium, France, the Netherlands and the USA. Samples were analysed in three laboratories. Quantitation was obtained for norandrostenedione, 19-nortestosterone and boldenone. The results give a well-documented overview of the status of the presence of these hormones in swine. The data illustrate that uncastrated 'old' boars produce the highest percentage of 'positive' matrices, followed by the cryptorchids. Concentrations in the matrices of the barrows and the gilts are lower. Also, sow matrices contain low amounts of nor-steroids. Furthermore, urine samples from an intersex pig contains a higher concentration of nortestosterone than sows and can therefore be suspected for illegal use of these hormones. Veterinarians taking samples in pig farms for the analysis of hormones need to be aware of the presence and concentrations of these substances in the different categories.

The effects of tumor necrosis factor on the production of interleukin-1 by macrophages.

We investigated the effect of tumor necrosis factor (TNF) on interleukin-1 (IL-1) production by mouse macrophages. At high doses of TNF, macrophages produced no IL-1 (as judged in the LAF assay) even when exposed to bacterial lipopolysaccharide (LPS), an excellent inducer of IL-1 production. In lower (picogram/ml) doses, TNF caused macrophages to make factors which showed modest activity in the LAF assay and that activity could be blocked by antibody to IL-1. TNF induces in low doses also the production of a factor(s) which synergizes with IL-1 in the LAF assay.

Use of advance directives: a social work perspective on the myth versus the reality.

The Directive to Physician (previously called Living Will) and Durable Power of Attorney for Healthcare Decisions documents are usually signed in the belief that one's wishes will be carried out in the future. Often, however, physicians and families discover that the documents are vaguely worded or leave the patient's intent and legal standing unanswered. Two additional documents that may aid the decision-making process are the Durable Power of Attorney for Healthcare Decisions and the Medical Ethics Decision Form. As important as such documents may become in the future, perhaps even more important will be the process individuals will go through defining what quality of life means to them by specifying their values and beliefs to their families and physicians before they face a crisis situation. Each individual has the right to choose or refuse medical treatment--the current struggle is for each individual to articulate his or her wishes based on a personal definition of quality of life set forth in a clear and legal framework.

Correlation between interleukin-1 production and engraftment of transplanted bone marrow stem cells in patients with lethal immunodeficiencies.

Interleukin-1 (IL-1) production by endotoxin-stimulated, cultured monocytes from 19 patients with lethal congenital immune disorders were studied and compared with normal controls. Lipopolysaccharide (LPS) stimulated IL-1 production was normal in three of three patients with Wiskott Aldrich syndrome (WAS), two of three combined immunodeficiency with T-cell predominance (CIDTP) and nine of 13 with severe combined immunodeficiency (SCID). Monocytes deficient in IL-1 production could be restored to normal production after incubation with indomethacin in three of five deficient patients. Monocytes from the other two patients could not be induced to generate IL-1, suggesting either an intrinsic deficiency or an alternate inhibitory mechanism as the basis for the IL-1 deficiency observed. In patients with SCID who were transplanted with HLA-haplotype disparate, T-cell depleted marrow without preparative chemotherapy, deficiency of monocyte IL-1 production was correlated with graft failure. Immune reconstitution was achieved in IL-1 deficient patients only when donor monocytes were also engrafted. We hypothesize that deficiencies of IL-1 production may contribute to the heterogeneous expression of combined immunodeficiencies, and may also restrict the engraftment and functional development of allogeneic lymphoid progenitors from a T-cell depleted marrow graft.

A gas chromatographic/mass spectrometric screening, confirmation, and quantification method for estrogenic compounds.

A method is described for the screening, quantification and confirmation of a variety of estronenic substances in animal tissues. A solid-phase extraction technique combined with a liquid/liquid extraction allows for rapid sample preparation and high throughput for the following compounds in bovine liver, muscle and kidney: diethylstilbestrol, dienestrol, hexestrol, zeranol, taleranol, zearalanone, zearalenone, zearalenol, estradiol and estriol. Gas chromatography/mass spectrometry and selected ion monitoring is used for the determination with detection limits ranging from 50 to 150 ppt.