Low body mass index is associated with increased mortality in patients with pelvic and acetabular fractures.

AIMS: Fractures of the pelvis and acetabulum are often the consequence of high energy trauma in young individuals or fragility fractures in osteoporotic bone. They can be life-threatening or life changing injuries. No published data exists comparing body mass index (BMI) and mortality for this patient group. The aim of this study was to identify if low BMI (<18.5) was a predictor of morbidity and mortality for patients with these injuries. PATIENTS AND METHODS: Of the 1033 patients with pelvic or acetabular fractures referred to a single level 1 major trauma centre (MTC) over a 4.5-year period (August 2015 - January 2020); we retrospectively analysed data for all admitted patients. Data was collected on demographics, injury pattern, operative intervention and complications. Comparison was made between patients that were underweight (BMI<18.5) and patients that were not. Both in-hospital and post discharge complications were recorded including pulmonary embolus (PE), deep venous thrombosis (DVT), ileus, infection, loss of reduction and mortality at 6 months. RESULTS: 569 patients admitted to the MTC with a pelvic or acetabular fracture were included in our analysis. Underweight patients had a statistically significant increase in mortality both in-hospital (p = 0.019) and at 6 months post injury (p = 0.039) when compared to other BMI groups. No statistical significance was found between these BMI groups comparing morbidity: DVT (p = 0.712), PE (p = 0.736) nor ileus (p = 0.149). Covariate analysis showed that a low BMI was associated with triple the in-hospital mortality after correction for age and energy of injury (adjusted OR 3.028, 95% CI 1.059-8.659). CONCLUSION: This is the first published study that demonstrates a statistically significant increase in mortality in patients with pelvic or acetabular fractures who are underweight. Surgeons should carefully consider appropriate peri-operative optimisation for these patients. Further investigation into the effects of low BMI and response to trauma is required.

High-level semi-synthetic production of the potent antimalarial artemisinin.

In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Efficacy and safety of a transdermal contraceptive system.

OBJECTIVES: To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. METHODS: In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. RESULTS: The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). CONCLUSIONS: The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

Initial 17beta-estradiol dose for treating vasomotor symptoms.

OBJECTIVE: To compare the efficacy of different doses of 17beta-estradiol (E2) for relief of vasomotor symptoms in menopausal women. METHODS: This was a randomized, double-masked, placebo-controlled, 12-week study in which 333 menopausal women with moderate or severe hot flushes were assigned to treatment with 0.25 mg, 0.5 mg, 1 mg, or 2 mg oral micronized 17beta-E2, or placebo. The number and severity of hot flushes were recorded daily. RESULTS: There was a significant linear correlation between increased dosage of 17beta-E2 and decreased moderate to severe hot flushes per week (P <.001). Rapid reduction in moderate to severe hot flushes was only achieved with 1 and 2 mg, showing a significant difference from placebo at week 4 (P <.05). At week 4, half the women on placebo had reduced moderate to severe hot flushes of at least 52%; the corresponding figures were 56%, 69%, 86%, and 91% for 0.25, 0.5, 1, and 2 mg, respectively. At week 12, all doses except 0.25 mg were significantly better than placebo for reducing moderate to severe hot flushes (P <.001). Although there were no significant differences, twice as many women in the 2-mg group discontinued treatment due to adverse events, compared with the placebo group. CONCLUSION: Oral micronized 17beta-E2 showed a dose-response effect for reducing moderate and severe hot flushes in menopausal women. 17beta-E2 1 mg appeared to be the most useful initial dose.

Relationship of antepartum pelvic examinations to premature rupture of the membranes.

A retrospective analysis of 273 term deliveries over a four-month period in an Air Force Regional Hospital revealed an 11% incidence of patients seen at term with premature rupture of membranes (PROM) and not in active labor who required induction of labor. The incidence of primary cesarean section in this group was found to be more than twice that of the remaining group of patients, who were seen early in labor with intact membranes, or who had spontaneous rupture of the membranes after the onset of labor. Although this incidence was not statistically significant, it did represent a worrisome trend. Therefore, a randomized prospective study was performed over the next six months to determine whether or not elective antenatal pelvic examinations might contribute to this problem. A total of 349 patients were studied. In 175 patients in whom no pelvic examinations were done until term or past term, the incidence of PROM was found to be 6%. In the 174 patients in whom pelvic examinations were done weekly starting at 37 weeks' gestation, the incidence was 18%, which was a significant increase (P = .001). The primary cesarean section rate was comparable in both groups with PROM; however, the overall primary cesarean section rate when PROM occurred was found to be twice that of the remaining population. This, however, did not achieve statistical significance. The study suggests that pelvic examinations before term may be a significant contributing factor to the incidence of PROM.