Pharmacoethics and pregnancy: Overcoming the therapeutic orphan stigma.

There is paucity of evidence to support clinical decision making and counselling related to medication use in pregnancy. Despite multiple efforts from legislative bodies and advocacy groups, the inclusion of pregnant women in clinical drug trials assessing efficacy and safety remains scarce. Pregnancy can be complicated by multiple comorbidities that require pharmacological intervention; these interventions primarily target the pregnant woman but also sometimes have secondary effects for the foetus. The US Food and Drug Administration has issued multiple guidance documents on incorporating pregnant women in clinical trials to aid pharmaceutical companies in designing a protocol to ensure safety and adherence to ethical standards. Advances in paediatric pharmacology studies provide lessons for researchers on the best practice of designing clinical trials with inclusion of patients from special populations. In this review, we present the status of pregnant women in clinical trials, highlighting the ethical stigma and possible future directives.

Effect of implementation of a colorimetric quantitative blood loss system for postpartum hemorrhage.

OBJECTIVE: To evaluate if the implementation of a colorimetric quantitative blood loss (QBL) system during cesarean delivery improves clinical outcomes. METHODS: We conducted a retrospective cohort analysis after cesarean section before and after implementation of the Triton based colorimetric QBL system. Prevalence of postpartum hemorrhage, amount of blood products transfused, length of hospitalization, and rates of intensive care unit (ICU) admission were compared. RESULTS: A total of 2221 patients were included. There were 1192 patients in the pre-intervention group and 1029 patients in the post-intervention group. There was no significant difference between groups in the prevalence of postpartum hemorrhage (8.6% vs 9.3%, P = 0.57), amount of packed red blood cells (pRBCs) transfused (45 vs 30, P = 0.41) or average length of hospital stay in days (3.0 vs 3.0, P = 0.37). There was a statistically significant decrease in ICU admissions between the pre- and post-intervention groups (2.2% vs 1.0%, P = 0.02). CONCLUSION: There was no effect of implementation of the colorimetric QBL application system on diagnosis of postpartum hemorrhage, amount of blood products transfused, or length of hospital stay. Although a significant decrease in ICU admissions was observed, we could not determine if these transfers were hemorrhage related.

Clinical characteristics, risk factors and microbiology of infections in patients receiving chronic hemodialysis.

BACKGROUND: The infectious complications in hemodialysis patients are still among the main reasons for their increased morbidity and mortality. The possible reasons behind this might be due to impairments in the host defense mechanisms, comorbidities, invasive procedures and pathogenicity of the infecting organisms. With the increased incidence of bacteremia in hemodialysis patients and the overt use of antibiotics, we have witnessed a rise in the number of new multidrug resistant (MDR) strains in those patients. AIM: We aim to determine the epidemiology, risk factors and complications of infections in patients receiving chronic hemodialysis, particularly bloodstream infections. METHODS: This is a retrospective case-control study involving patients undergoing hemodialysis at a tertiary care center. We studied the prevalence of infectious complications among those patients as well as the responsible agent in each respective infectious episode and the risk factors associated with bacteremia. FINDINGS: 46.6% of the studied population had at least one documented episode of infection. The most common were blood and respiratory infections (33.2% and 32.7% respectively). Among patients with bacteremia, coagulase-negative Staphylococcus was the predominant pathogen (49% of cases), followed by Staphylococcus aureus and Escherichia coli. Mortality was higher in patients who had MDR bacteremia, and in those who had mechanical ventilation or intensive care unit (ICU) admission. CONCLUSION: Due to the alarming increase in the incidence of infection among hemodialysis patients and its strong association with mortality, further studies are needed to look for risk factors associated with infection and for ways to control those risk factors.

Cost variance across obesity class for women undergoing laparoscopic hysterectomy by high-volume gynecologic surgeons.

Health-care costs are affected by obesity with both the direct and indirect costs of health care increasing as body mass index (BMI) increases. However, one important aspect of obesity that lacks rigorous study is what impact BMI has on direct surgical cost. We performed a retrospective cohort study of women undergoing a laparoscopic hysterectomy at our single academic university center between January 2012 and December 2017. Women were excluded if their surgery was performed by anyone other than those surgeons with subspecialty training in minimally invasive gynecologic surgery (MIGS), if their hysterectomy was performed by a modality other than conventional laparoscopy or with robotic assistance, or if the indication for hysterectomy was related to any gynecologic malignancy. We identified 600 patients who underwent laparoscopic hysterectomy during the study period. Women who underwent robotic hysterectomy, compared to laparoscopic, had a shorter operative time, lower estimated blood loss, and shorter length of stay. Mean direct cost (± standard deviation) for the cohort was $6398.53 ± $2304.67, age was 44.5 ± 7.5 years, and BMI was 32.2 ± 7.6. Direct cost for all laparoscopic hysterectomies was evaluated across the five different BMI quintiles and no significant difference between groups was found. There was no significant difference in direct cost across procedures between obese and non-obese patients (p = 0.62) and this remained true when separated out by surgical modality. However, when evaluating morbidly obese patients, there appears to be a trend toward cost reduction with robotic hysterectomy compared to conventional laparoscopy. It does not appear that BMI has a statistically significant impact on direct cost between robotic-assisted and conventional laparoscopic hysterectomy. However, these findings may be due to surgical proficiency and warrant further investigation among surgeons with lesser volume.

Anatomical and physiological alterations of pregnancy.

The extensive metabolic demands of pregnancy require specific physiological and anatomical changes. These changes affect almost all organ systems, including the cardiovascular, respiratory, renal, gastrointestinal, and hematologic system. The placenta adds another layer of complexity. These changes make it challenging for clinicians to understand presenting signs and symptoms, or to interpret laboratory and radiological tests. Furthermore, these physiological alterations can affect the pharmacokinetics and pharmacodynamics of drugs. Drug safety in lactation is only supported by limited evidence. In addition, the teratogenic effects of medications are often extrapolated from animals, which further adds uncertainties. Unfortunately, pregnant women are only rarely included in clinical drug trials, while doses, regimens, and side effects are often extrapolated from studies conducted in non-pregnant populations. In this comprehensive review, we present the changes occurring in each system with its effects on the pharmacokinetic variables. Understanding these physiological changes throughout normal pregnancy helps clinicians to optimize the health of pregnant women and their fetuses. Furthermore, the information on pregnancy-related physiology is also critical to guide study design in this vulnerable 'orphan' population, and provides a framework to explore pregnancy-related pathophysiology such as pre-eclampsia.

Blood type association with bleeding outcomes at delivery in a large multi-center study.

Postpartum hemorrhage is a leading cause of maternal death globally. Recent studies have associated Type-O group to increased risk of bleeding. We aimed to determine if women with Type-O blood are at higher risk of PPH. This is a retrospective cohort analysis of a multi-center database included women admitted to labor and delivery from January 2015 to June 2018. All deliveries resulting in live birth were included. Association between Type-O and non Type-O were examined using chi-square test and fishers exact test. Prevalence of postpartum hemorrhage, estimated blood loss, drop in hematocrit and red blood cell transfusion were compared. The matched sample included 40,964 Type-O and the same number of no Type-O. The overall prevalence of postpartum hemorrhage was 6.4%, and there was no difference in the prevalence of PPH among Type-O compared to non Type-O (6.38% vs. 6.37% respectively; p = 0.96). There was no difference in hematocrit drop and estimated blood loss between Type-O and non Type-O in all deliveries. However, in cesarean delivery there was a significant difference in blood loss among the two groups. Finally, Type-O had 1.09-fold increased risk for transfusion compared to non Type O (95% CI 0.9-1.34). There is an association between Type-O group and risk of bleeding in women undergoing cesarean delivery. More prospective studies, taking into account coagulation profile, platelet count and tissue factors, are needed to draw a conclusion on whether ABO system can be considered a heritable risk of postpartum hemorrhage.