Titrated oral misoprostol given for labour augmentation produces vaginal delivery rates similar to intravenous oxytocin, according to a new randomized clinical trial.

But more clinical trials should be done in order to determine the optimum initial dosage in Western populations, said researchers from China Medical University .

Oral misoprostol is easier to administer than IV oxytocin, and it also has a longer shelf life and is stable at room temperature, noted researchers. While concerns have been raised that misoprostol could lead to foetal distress due to excessive uterine contractility, the drug is less likely to produce uterine hyperstimulation, noted researchers.

The researchers randomly assigned 231 women who went into spontaneous labour at 36 to 42 weeks' gestation and were having "inadequate uterine contractions" during the first stage of labour (defined as two or fewer contractions every 10 minutes) to receive titrated oral misoprostol or IV oxytocin. All study participants were having regular contractions and had cervical dilation of 3 to 9 centimetres.

Among the 118 women given misoprostol, median time to vaginal delivery after the start of augmentation was 5.22 hours, compared to 5.20 hours for the 113 women in the oxytocin groups. Caesarean section deliveries were performed in 10.2 percent of the women given misoprostol and 11.5 percent of women given oxytocin (P=.744).

Seventy-eight percent of women in the misoprostol group had complete vaginal delivery within 12 hours, compared to 85.8 percent of women in the oxytocin group (P=.121). The percentage of women who had delivered within 24 hours was similar, as were rates of side effects and neonatal outcomes.

The researchers used an initial misoprostol dosage of 20 micrograms, with a maximal cumulative dosage of 320.0 micrograms, while the maximal oxytocin dosing rate was 10 milliunits per minute, the researchers note. Average total dosage was 60.0 micrograms for misoprostol and 1,225.0 milliunits for oxytocin.

One disadvantage of oxytocin is that it is ineffective for cervical ripening. When the Bishop score is less than 7, the method of titrated oral misoprostol is better than that of titrated intravenous oxytocin, the researcher said. However, when the Bishop score is equal to or greater than 7, the method of titrated intravenous oxytocin is better than that of titrated oral misoprostol.

Misoprostol also commonly produced side effects in this study population such as nausea, vomiting, shivering and pyrexia, whereas oxytocin did not.

Researchers also emphasized that the dosage, timing and choice of agent for labour induction or augmentation must be individualized based on the patient's response and the pharmacokinetics of the drug.

An analysis of data from Denmark found no associated increased risk of major birth defects for mothers who were exposed during the first trimester of pregnancy to the antiviral drugs acyclovir, valacyclovir, and famciclovir.

The prevalence of herpes simplex is high, and more than 1% of susceptible women acquire herpes simplex during the first trimester of pregnancy, with antiviral treatment indicated for a significant number of women in pregnancy. Although the safety of acyclovir, valacyclovir, and famciclovir in general has been well established, data on the use of these antivirals in early pregnancy are limited, the authors wrote.

Researchers conducted a registry-based study to assess associations between acyclovir, valacyclovir, and famciclovir use in the first trimester of pregnancy and major birth defects. The study included 837,795 live-born infants in Denmark from January 1996 to September 2008.

Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses, and potential confounders.

Among 1,804 pregnancies exposed to acyclovir, valacyclovir or famciclovir at any time in the first trimester, 40 infants (2.2%) had a diagnosis of a major birth defect, compared with 19,920 of 835,991 infants (2.4%) among the unexposed pregnancies.

Adjusting for several variables, acyclovir, valacyclovir or famciclovir exposure at any time in the first trimester was not associated with increased risk of major birth defects.

First-trimester use of acyclovir, the most commonly prescribed antiviral, was not associated with major birth defects (32 cases among 1,561 exposed [2.0%] vs 2.4% in the unexposed). Neither valacyclovir (7 of 229 infants [3.1%]) nor famciclovir (1 of 26 infants [3.8%]) were associated with major birth defects, although use of famciclovir was uncommon.

Additional analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small.

The study found no significant association between first-trimester exposure to antiherpetic antiviral drugs and major birth defects, the authors wrote. Acyclovir is the most extensively documented antiviral and should therefore be the drug of choice in early pregnancy, while data on valacyclovir and famciclovir are still insufficient. Future research on antiherpetic antivirals and mother-child health should include safety studies with regard to spontaneous abortion and preterm birth, and during breastfeeding, said researchers.

JAMA . 2010;304:859-866, 905-906.

In a region where malaria is endemic, withholding antimalarials in febrile children with a negative rapid diagnostic test for malaria (RDTm) doesn't increase their risk of complications or death, according to a prospective study.

There were no malaria complications or deaths in febrile kids with negative RDTm results and no antimalarial treatment, the study team reported.

The study included a thousand children, enough to allow researchers to say with 95% confidence that the probability of such an unfavourable event was between 0% and 0.5% (rule of 3).

RDT is a safe tool to diagnose malaria, even in small children living in highly endemic areas. As long as quality control is insured, RDT can replace microscopy in non-severe cases of all age groups, said researchers.

The study, carried out in two areas of Tanzania that are moderately and highly endemic for malaria (1 urban, 1 rural), included 1,000 children (median age, 24 months) who were feverish at enrolment. All were managed routinely, with one exception: no antimalarials were prescribed when the RDTm was negative, which was the case in 60% (603 of 1,000).

The primary outcome was the rate of complications and deaths, irrespective of parasitemia, the researchers noted in their report.

Twelve children (2%) with an initial negative RDTm test result were lost to follow-up. Among the remaining 591 children, 573 (97%) were cured by day 7. Among the remaining 18 children, 15 were examined on or before day 7 because of fever, 2 because of diarrhoea and 1 because of headache. Fourteen of these 18 children were cured on day 14, 2 died (of causes other than malaria) and 2 were lost to follow up.

All but 3 children who had negative RDTm results initially had negative results again when retested either at spontaneous attendance to the clinic or on day 7. None of these 3 children experienced any complications.

This study provided "strong evidence" that a strategy of withholding antimalarial treatment in the face of a negative RDTm test is safe, irrespective of endemicity of malaria.

RDTs may miss some clinically uncomplicated malaria infections, these are probably mainly low-density infections and only rarely will they develop into severe malaria manifestations, said researchers

Researchers said that the findings do not directly apply to resource-rich settings, where most of the travellers and migrants returning with fever are non-immune towards malaria and where resources are available to perform more than one type of test simultaneously.

RDTs should be used on top of microscopy in non-endemic countries to increase sensitivity and reduce the delay before treatment, suggested researchers.

http://www.mdaap.org/forum/showthread.php?p=7587. Last accessed on 30.08.10

Deliberate inoculation with Escherichia coli 83972 may help patients with incomplete bladder emptying and recurrent urinary tract infections, reported Swedish researchers.

Researchers found that E. coli bacteriuria delayed recurrence of self-reported infections by more than five months on average.

Spontaneously developed asymptomatic bacteriuria (ABU) is good for the patient and should not be treated, said researchers.

For those who don't develop ABU on their own, the new results show doctors may consider inoculating them with E. coli 83972.

Researchers randomized 26 patients with incomplete bladder emptying and recurrent urinary tract infections (UTI) to either saline or E. coli 83972 inoculations. The patients switched treatment after the first urinary tract infection or at 12 months.

Twenty patients completed the study. There were no significant side effects in the inoculated patients and no febrile UTI episodes.

The median time to UTI development was 11.3 months in patients with bacteriuria and 5.7 months in those receiving saline (p=0.013).

After the cross-over trial had been completed, the patients continued in a one-year observational part of the study, also blinded and placebo-controlled. There were 13 infections in the bacteriuria group and 35 in the saline group (p=0.009). Minor symptoms were less common in patients with bacteriuria, although the difference was not significant (17 vs. 28, p=0.13).

The procedure is not US FDA approved but with increasing antibiotic resistance, this approach will be more important, said researchers.

J Urol. 2010;184 (1):179-85

Data from more than 84,000 women over 26 years suggested that shifting dietary protein sources away from red meat to more poultry, fish, and nuts can reduce an individual's risk of coronary heart disease.

Researchers analyzed data from 26 years of follow-up from 84 135 women, aged 30 to 55 years, in the Nurses' Health Study. The patients enrolled in the study had no known cancer, diabetes mellitus, angina, MI, stroke, or other cardiovascular disease. Their diet was tracked with a standard questionnaire every four years. During 26 years of follow-up, 2210 incident nonfatal infarctions and 952 deaths from coronary heart disease were reported.

A multivariable analysis of diet and traditional risk factors, such as age and smoking, showed that consumption of red meat and high-fat dairy were significantly associated with an elevated risk of coronary heart disease, whereas higher intakes of poultry, fish, and nuts were significantly associated with lower risk.

A statistical model controlling for total intake of calories, cereal fiber, alcohol, trans-unsaturated fatty acids, and other potential non-dietary confounding variables showed that one serving per day of nuts was associated with a 30% lower risk of coronary disease than one serving per day of red meat. The same one-serving exchange comparison found a 13% lower risk with low-fat dairy, a 19% lower risk with poultry, and a 24% lower risk with fish.

This latest analysis from the study affirms the findings from 14 years and 16 years of follow-up, and red meat continues to be significantly related to coronary disease risk, independent of measured confounders and known intermediate outcomes.

The authors also found a link between total meat intake and coronary disease risk, likely driven by the high proportion of red meat in the total meat intake, but the strong association between red meat and coronary disease cannot be entirely explained by the intake of processed meat, because red meat remained associated with coronary disease even when processed meat was excluded. However, a recent study by a researcher at Boston found that eating unprocessed red meat did not increase the risk of coronary heart disease or diabetes, but eating 50 g of processed meat per day was associated with a 42% higher risk of CHD and a 19% increased risk of diabetes, most likely because of the volume of sodium and other preservatives.

The authors recalled that dietary iron, particularly the heme iron found in red meat has been positively associated with MI and fatal coronary disease in most, but not all, previous studies. The effect of heme iron on systolic blood pressure, the high sodium content of processed meats, and the compounds created by cooking red meat, such as heterocyclic amines and advanced glycation end products, might also increase coronary risk.

When major sources of protein, such as nuts and fish, are used to replace red meat; saturated fat, heme iron, and sodium decrease, whereas intake of polyunsaturated fat increases. The benefit on CHD risk of such a substitution is thus likely to be due to multiple simultaneous changes in nutrient intake, concluded researchers.

Circulation 2010; DOI:10.1161/circulationaha.109.915165. http://circ.ahajournals.org/.
Last accessed on 30.08.10.