Clinical interventions to reduce stillbirths in sub-Saharan Africa: a mathematical model to estimate the potential reduction of stillbirths associated with specific obstetric conditions.

OBJECTIVE: Stillbirths are among the most common adverse pregnancy outcomes, with 98% occurring in low-income countries. More than one-third occur in sub-Saharan Africa (SSA). However, the medical conditions causing stillbirths and interventions to reduce stillbirths from these conditions are not well documented. We estimated the reductions in stillbirths possible with combinations of interventions. DESIGN: We developed a computerised model to estimate the impact of various interventions on stillbirths caused by the most common conditions. The model considered the location of obstetric care (home, clinic or hospital) and each intervention's efficacy, penetration and utilisation. Maternal transfers were also considered. SETTING AND POPULATION: Pregnancies in SSA in 2012. METHODS: For each condition, we created a series of scenarios involving different combinations of interventions and modelled their impact on stillbirth rates. MAIN OUTCOME MEASURES: Stillbirths associated with various maternal and fetal conditions and the percentage reduction with various interventions. RESULTS: Eight to ten maternal and fetal conditions were responsible for most stillbirths, but none for more than 15%. The most common conditions causing stillbirths in SSA include obstructed labour and uterine rupture, fetal distress and umbilical cord complications, fetal growth restriction, pre-eclampsia/eclampsia, and placental abruption/placenta praevia. Syphilis and malaria contribute smaller numbers. Reducing stillbirths requires appropriate diagnosis and management of each condition, usually including hospital care for monitoring and delivery, often by caesarean section. Maternal syphilis and malaria were the only conditions for which outpatient management alone reduced stillbirth. CONCLUSIONS: Most stillbirths in low-income countries occur at term and during labour and therefore are preventable by appropriate obstetric care. Management focused on the maternal and fetal conditions that cause stillbirths is necessary to achieve stillbirth rates approaching those found in high-income countries. TWEETABLE ABSTRACT: Reducing stillbirth incidence requires appropriate management of each causative condition and often caesarean delivery.

Tetrachloroethylene intoxication in an autoerotic fatality.

This case report describes an accidental death due to the inhalation of tetrachloroethylene during an autoerotic episode. Tetrachloroethylene was administered from a can of Fix-A-Flat tire repair. Analysis of tetrachloroethylene was performed using headspace gas chromatography and electron capture detection. The blood tetrachloroethylene concentration of 62 mg/L was consistent with acute tetrachloroethylene intoxication.

Role of the toxicology laboratory in suspected ingestions.

The toxicology laboratory can fill an important role in improving patient care. Whether the service provided by the laboratory is specifically in support of a pediatric population or devoted more to the entire hospital population, the considerations involved in its configuration are the same. These considerations involve establishment of an open dialogue between the laboratory and clinical staff, an integrated and comprehensive analytic approach, and provision of reliable laboratory data in a timely fashion.

Role of the toxicology laboratory in the treatment of acute poisoning.

The modern toxicology laboratory can play an important role in the evaluation of poisoning. In order to appreciate the nature and extent of this role, several essential elements necessary to an acute care toxicology service should be considered. When an ongoing and effective dialogue between clinicians and the toxicology laboratory staff is established, and a broadly based analytical approach is applied to the analysis of the appropriate biological fluids, a dynamic and viable toxicology service will result. How these elements work together to facilitate this service will be discussed, based primarily on experience in a large teaching hospital. This experience indicates that if the elements necessary to provide laboratory support in the investigation of an alleged poisoning are in place, the toxicology laboratory plays an important role in ensuring optimum and effective patient care.

Detection and confirmation of urinary cannabinoids.

Both a thin layer chromatographic procedure (TOXI-LAB) and two homogeneous immunoassays with differing sensitivity limits (EMIT-st, and EMIT d.a.u.) were used to test 525 urine specimens for metabolites of tetrahydrocannabinol. Negative results were obtained by all techniques for 283 specimens. The EMIT-st was positive for 184 specimens, the EMIT-d.a.u. for 47 additional specimens. The TOXI-LAB results were positive for all these 231 specimens. An additional 11 specimens were positive by EMIT-d.a.u. and negative by TOXI-LAB. Gas chromatography/mass spectrometry analyses of five of these 11 indicated that their average 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid concentration was 7.4 +/- 2.2 ng/mL, well below the lower detection limit of the TOXI-LAB procedure. Using both EMIT-d.a.u. and TOXI-LAB assures a reliable urinary cannabinoid analysis above a concentration of 25 ng/mL.

Homogeneous enzyme immunoassay of acetaminophen in serum.

A new commercially available homogeneous enzyme immunoassay, using the glucose-6-phosphate dehydrogenase (G6PDH) catalyzed conversion of NAD to NADH, has been evaluated and applied to the determination of acetaminophen in serum. Replicate analysis of serum control samples over the range of 10-200 micrograms/mL demonstrated a within-assay coefficient of variation of less than or equal to 4.6% and a between-assay coefficient of variation of less than or equal to 5.8%. Regression analysis of two separate groups of 98 and 47 serum samples by this technic, using different reagent lots, and a HPLC reference method gave equations of y = 0.981x - 0.941 (r = 0.984) and y = 1.06x - 2.21 (r = 0.994), respectively. No interference due to hemolysis or turbidity was noted. Evaluation of samples containing 35 commonly prescribed or over the counter medications demonstrated no significant cross-reactivity. Prepared reagents were stable over a period of at least 2 months when stored at 4 degrees C. Correlations between two reagent lots were excellent (r = 0.998). A single sample can be analyzed expeditiously. The result may help evaluate a potential acetaminophen poisoning. Another way to assess this toxicity, calculation of the elimination half-life, has limitations that depend on the precision of the analysis.

Combined enzyme immunoassay-LCEC method for the identification, confirmation, and quantitation of opiates in biological fluids.

An enzyme multiplied immunoassay technique (EMIT) was used to test for opiates (morphine, hydromorphone, and codeine) in extracts of blood, bile, and tissue homogenates. All immunoassay opiate positive specimens were then tested by a reversed-phase liquid chromatographic procedure using electrochemical detection (LCEC). Blood specimens were then quantitated by LCEC. The sensitivity of the immunoassay (as morphine) was 0.020 mg/L, 0.200 mg/L, and 0.100 mg/kg for blood, bile, and tissue homogenates, respectively, with 2% intrarun and 7% interrun precision. The LCEC method was linear from 0.005 to 0.300 mg/L for morphine, hydromorphone, and codeine (nalorphine internal standard) with detection limits of 0.005 mg/L for each analyte. Intrarun and interrun precision varied from 1 to 2% and 6 to 11%, respectively. Recoveries, using a double extraction technique, ranged from 70 to 95%. These two methods, applied to 495 post mortem cases, demonstrated a 6% incidence of opiates, with no false positives.

The role of the toxicology laboratory in emergency medicine.II: Study of an integrated approach.

The utility of the toxicology laboratory in emergency medicine is directly related to both establishing communication between the toxicology laboratory and the clinical staff, and to providing reliable toxicology data while the diagnostic process is still in progress. When 604 patients, on whom a "complete toxicology screen" was requested, were evaluated using qualitative probes involving chemical spot tests, immunoassay, TLC and/or selected GC/HPLC methods, the resulting data were demonstrated to be of value. The ability of the clinician to accurately predict which, if any, of a large number of intoxicants were present in a given patient, was found to be minimal and as a result these combined tests were found to be essential in facilitating a proper diagnosis. Additionally, it was found that using only chemical spot tests, immunoassay and TLC in a combined qualitative approach detected 94-98% of all the substances eventually found within the population when it was further studied using more sophisticated instrumental methods. The integrated approach involving the initial establishment of a dialogue between the clinician and the toxicologist, use of simple qualitative analytical probes, confirmation of positive findings and prompt reporting of toxicology data is a viable way in which meaningful toxicology support can be provided while the diagnostic process is still underway.

EMIT-st screening for drugs of abuse: methaqualone.

The Emit-st (single test) drug detection system was determined, for methaqualone and several of its metabolites, to be reliable and simple to perform. Its sensitivity was 0.3 micrograms/mL for methaqualone and 0.4 micrograms/mL for the only methaqualolne metabolite (4-hydroxymethaqualone) known to be excreted unconjugated. This assay also detects mecloqualone, a Schedule I drug marketed in Europe and South Africa.

Acute loxapine intoxication in a child.

Thin-layer chromatography (TLC) was used to confirm the alleged ingestion of Loxitane (loxapine succinate) by a 20-month-old child. GC was used to further characterize TLC spots and to quantitate the loxapine concentration of the blood at 0.072 mg/dL, which was consistent with the child's presenting signs of lethargy and ataxia. The appropriate supportive symptomatic therapy, with monitoring for CNS and cardiovascular toxicities, resulted in an uneventful recovery.

The role of the toxicology laboratory in emergency medicine.

The toxicology laboratory can provide diagnostic and prognostic information relevant to an alleged acute poisoning. To do this effectively, the clinician must cooperate by providing suitable specimens to and dialogue with the laboratory. The many simple laboratory tests that enable prompt qualitative results relevant to diagnosis as well as those more elegant procedures required for prognosis are briefly described. The toxicologist, by promptly reporting the results of these tests to the clinician and assisting in their interpretation, helps insure optimal patient care.

Clinical application and evaluation of the Emit-stTM drug detection system.

A critical evaluation of a newly devised homogeneous assay system, Emit-stTM, for ethanol, opiates, barbiturates and benzodiazepines indicates they are class specific, simple to perform, completed quickly and more than sensitive enough to detect concentrations of the analytes at levels compatible with overdoses. By using this technic clinical diagnoses of acute poisonings can be improved.

An evaluation of the overestimation of serum albumin by bromcresol green.

Repeated observations have shown that the bromcresol green method overestimates serum albumin. Random patient serum samples were analyzed by a bromcresol green method using the Technicon AutoAnalyzer and by serum protein electrophoresis using cellulose acetate. The mean AutoAnalyzer value was 4.29 g/dl and the mean protein electrophoresis value was 3.68 g/dl (r = 0.915, slope = 0.869, y intercept = 1.090 g/dl where bromcresol green is on the Y axis, n = 166). Studies of the interference of proteins other than albumin in the bromcresol green method using the Technicon AutoAnalyzer showed that alpha globulins produce approximately a third, beta globulins a ninth, fibrinogen a fifth and hemoglobin equal the color intensity with the bromcresol green reagent that a comparable weight of albumin produced. In the bromcresol green method using the Du Pont ACA the interferences were even greater. At present, serum protein electrophresis is the most reliable method generally available to measure serum albumin. A modified bromcresol green method or immunoassay may eventually prove to be the method of choice.