Assessing Nephrology Fellows' Skills in Communicating About Kidney Replacement Therapy and Kidney Biopsy: A Multicenter Clinical Simulation Study on Breaking Bad News.

RATIONALE & OBJECTIVE: Interpersonal communication skills and professionalism competencies are difficult to assess among nephrology trainees. We developed a formative "Breaking Bad News" simulation and implemented a study in which nephrology fellows were assessed with regard to their skills in providing counseling to simulated patients confronting the need for kidney replacement therapy (KRT) or kidney biopsy. STUDY DESIGN: Observational study of communication competency in the setting of preparing for KRT for kidney failure, for KRT for acute kidney injury (AKI), or for kidney biopsy. SETTING & PARTICIPANTS: 58 first- and second-year nephrology fellows assessed during 71 clinical evaluation sessions at 8 training programs who participated in an objective structured clinical examination of simulated patients in 2017 and 2018. PREDICTORS: Fellowship training year and clinical scenario. OUTCOME: Primary outcome was the composite score for the "overall rating" item on the Essential Elements of Communication-Global Rating Scale 2005 (EEC-GRS), as assessed by simulated patients. Secondary outcomes were the score for EEC-GRS "overall rating" item for each scenario, score < 3 for any EEC-GRS item, Mini-Clinical Examination Exercise (Mini-CEX) score < 3 on at least 1 item (as assessed by faculty), and faculty and fellow satisfaction with simulation exercise (via a survey they completed). ANALYTICAL APPROACH: Nonparametric tests of hypothesis comparing performance by fellowship year (primary goal) and scenario. RESULTS: Composite scores for EEC-GRS overall rating item were not significantly different between fellowship years (P = 0.2). Only 4 of 71 fellow evaluations had an unsatisfactory score for the EEC-GRS overall rating item on any scenario. On Mini-CEX, 17% scored < 3 on at least 1 item in the kidney failure scenario; 37% and 53% scored < 3 on at least 1 item in the AKI and kidney biopsy scenarios, respectively. In the survey, 96% of fellows and 100% of faculty reported the learning objectives were met and rated the experience good or better in 3 survey rating questions. LIMITATIONS: Relatively brief time for interactions; limited familiarity with and training of simulated patients in use of EEC-GRS. CONCLUSIONS: The fellows scored highly on the EEC-GRS regardless of their training year, suggesting interpersonal communication competency is achieved early in training. The fellows did better with the kidney failure scenario than with the AKI and kidney biopsy scenarios. Structured simulated clinical examinations may be useful to inform curricular choices and may be a valuable assessment tool for communication and professionalism.

Managing glomerular disease in pregnancy.

Glomerular disease, especially lupus nephritis, is common in young women of childbearing age. As such, practicing nephrologists must have adequate knowledge and expertise to prepare these women for pregnancy, to diagnose and manage the numerous pregnancy-associated complications that are common in this vulnerable patient population and finally to support these young women who often struggle to manage both their young children along with an often onerous chronic disease. In this article we will review the pre-pregnancy counseling these women should ideally receive to allow them to make an informed decision about proceeding with a pregnancy, an approach to the diagnosis of pregnancy-associated worsening of kidney function and proteinuria as well as pregnancy-safe management strategies, including immunosuppression, antihypertensive agents and other medications necessary for the management of nephrotic syndrome. Gaps in our current knowledge and opportunities for collaborative research will be discussed throughout.

Severe rhabdomyolysis secondary to adenovirus infection: case report and literature review.

A 38-year-old male presented with renal failure in the setting of a flu-like illness. Urinalysis showed myoglobinuria and granular casts. His serum creatine phosphokinase was markedly elevated. He was diagnosed with rhabdomyolysis and was volume resuscitated with normal saline and bicarbonate-containing fluid. Workup included a respiratory viral panel which was positive for adenovirus. Other causes such as trauma, seizure, and intoxicants were excluded. He developed progressive renal failure necessitating hemodialysis. After ~ 4 weeks he recovered renal function and dialysis was discontinued. Viral-induced myopathy should be suspected in patients who present with rhabdomyolysis.

Circulating Levels of sFlt1 Splice Variants as Predictive Markers for the Development of Preeclampsia.

Angiogenic biomarkers, including soluble fms-like tyrosine kinase 1 (sFlt1), are thought to be predictors of preeclampsia onset; however, improvement is needed before a widespread diagnostic test can be utilized. Here we describe the development and use of diagnostic monoclonal antibodies specific to the two main splice variants of sFlt1, sFlt1-1 and sFlt1-14. These antibodies were selected for their sensitivity and specificity to their respective sFlt1 isoform in a capture ELISA format. Data from this pilot study suggest that sFlt1-1 may be more predictive of preeclampsia than total sFlt1. It may be possible to improve current diagnostic platforms if more specific antibodies are utilized.

Patients' priorities for treatment decision making during periods of incapacity: quantitative survey.

OBJECTIVE: Clinical practice aims to respect patient autonomy by basing treatment decisions for incapacitated patients on their own preferences. Yet many patients do not complete an advance directive, and those who do frequently just designate a family member to make decisions for them. This finding raises the concern that clinical practice may be based on a mistaken understanding of patient priorities. The present study aimed to collect systematic data on how patients prioritize the goals of treatment decision making. METHOD: We employed a self-administered, quantitative survey of patients in a tertiary care center. RESULTS: Some 80% or more of the 1169 respondents (response rate = 59.8%) ranked six of eight listed goals for treatment decision making as important. When asked which goal was most important, 38.8% identified obtaining desired or avoiding unwanted treatments, 20.0% identified minimizing stress or financial burden on their family, and 14.6% identified having their family help to make treatment decisions. No single goal was designated as most important by 25.0% of participants. SIGNIFICANCE OF RESULTS: Patients endorsed three primary goals with respect to decision making during periods of incapacity: being treated consistent with their own preferences; minimizing the burden on their family; and involving their family in the decision-making process. However, no single goal was prioritized by a clear majority of patients. These findings suggest that advance care planning should not be limited to documenting patients' treatment preferences. Clinicians should also discuss and document patients' priorities for how decisions are to be made. Moreover, future research should evaluate ways to modify current practice to promote all three of patients primary goals for treatment decision making.

Gestational angiogenic biomarker patterns in high risk preeclampsia groups.

OBJECTIVE: Several conditions are associated with increased preeclampsia (PE) risk. Whether altered maternal angiogenic factor levels contribute to risk in these conditions is unknown. Our objective was to compare angiogenic biomarker patterns in high-risk pregnancies and low-risk controls. STUDY DESIGN: We conducted a planned secondary analysis of a 2-center observational study of angiogenic biomarkers in high-risk women. A total of 156 pregnant women with a PE risk factor and 59 low-risk controls were studied. Serial maternal serum samples were collected during 3 gestational windows: 23-27 weeks, 28-31 weeks, and 32-35 weeks. Soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay. Geometric mean angiogenic biomarker levels and angiogenic ratio (sFlt1 + sEng):PlGF were compared with low-risk controls for each risk group, at each gestational window. RESULTS: Gestational biomarker patterns differed in PE risk groups as compared with low-risk controls. Women with multiple gestations had markedly higher sFlt1 and sEng at all gestational windows. Women with prior PE had higher sFlt1 and angiogenic ratio, and lower PlGF, from 28 weeks onward. Women with chronic hypertension had significantly higher angiogenic ratio for all 3 gestational windows, but differences disappeared when women with PE were excluded. Obese and nulliparous women had significantly lower PlGF, but no differences in the angiogenic ratio. CONCLUSION: High-risk groups have altered angiogenic biomarker patterns compared with controls, suggesting that altered production or metabolism of these factors may contribute to PE risk, particularly in women with multiple gestations and prior PE.

Light chain cast nephropathy caused by plasmablastic lymphoma of the bladder.

INTRODUCTION: Plasmablastic lymphoma (PBL) is a rare form of B-cell lymphoma typically seen in patients with underlying immunosuppression such as HIV, autoimmune disease, and organ transplantation. PBL in HIV-positive patients usually originates from the gastrointestinal tract, with a predilection for the oral cavity. Bladder involvement by PBL is exceedingly rare, and cast nephropathy due to κ light chain-secreting PBL has not been reported previously. CASE REPORT: We report a patient who presented with acute kidney injury (AKI) in the setting of HIV, and was found to have a bladder tumor. Bladder pathology revealed a high-grade PBL with κ light chain restriction. Renal biopsy showed κ light chain cast nephropathy, presumably secondary to κ light chain-secreting PBL. CONCLUSION: Although the prognosis of PBL is poor, our patient recovered from AKI, achieved complete hematologic remission with chemotherapy, and underwent successful autologous stem cell transplant.

Pregnancy and the kidney.

Nephrologists are frequently called on to diagnose and treat renal disorders in pregnant women. In this review, we update recent literature pertinent to pregnancy and renal disease. We initially begin by describing the application of common clinical estimators of GFR and proteinuria in pregnancy and then summarize recent studies regarding pregnancy in women with chronic kidney disease and the latest information on the use of common renal medications in pregnancy. In the final section, we describe advances in our understanding of the pathophysiology of preeclampsia and the potential clinical implications of these discoveries for screening, prevention, and treatment of preeclampsia.

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.

BACKGROUND: Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in the pathogenesis of preeclampsia. Since soluble endoglin, another antiangiogenic protein, acts together with sFlt1 to induce a severe preeclampsia-like syndrome in pregnant rats, we examined whether it is associated with preeclampsia in women. METHODS: We performed a nested case-control study of healthy nulliparous women within the Calcium for Preeclampsia Prevention trial. The study included all 72 women who had preterm preeclampsia (<37 weeks), as well as 480 randomly selected women--120 women with preeclampsia at term (at > or =37 weeks), 120 women with gestational hypertension, 120 normotensive women who delivered infants who were small for gestational age, and 120 normotensive controls who delivered infants who were not small for gestational age. RESULTS: Circulating soluble endoglin levels increased markedly beginning 2 to 3 months before the onset of preeclampsia. After the onset of clinical disease, the mean serum level in women with preterm preeclampsia was 46.4 ng per milliliter, as compared with 9.8 ng per milliliter in controls (P<0.001). The mean serum level in women with preeclampsia at term was 31.0 ng per milliliter, as compared with 13.3 ng per milliliter in controls (P<0.001). Beginning at 17 weeks through 20 weeks of gestation, soluble endoglin levels were significantly higher in women in whom preterm preeclampsia later developed than in controls (10.2 ng per milliliter vs. 5.8 ng per milliliter, P<0.001), and at 25 through 28 weeks of gestation, the levels were significantly higher in women in whom term preeclampsia developed than in controls (8.5 ng per milliliter vs. 5.9 ng per milliliter, P<0.001). An increased level of soluble endoglin was usually accompanied by an increased ratio of sFlt1:PlGF. The risk of preeclampsia was greatest among women in the highest quartile of the control distributions for both biomarkers but not for either biomarker alone. CONCLUSIONS: Rising circulating levels of soluble endoglin and ratios of sFlt1:PlGF herald the onset of preeclampsia.

Association of cotinine levels and preeclampsia among African-American women.

INTRODUCTION: Although prior studies have shown that smoking reduces preeclampsia risk, the relationship between nicotine level and preeclampsia risk is not known. Our objective was to study the effects of smoking on the incidence of preeclampsia in African-American women using cotinine, a quantitative marker of nicotine. METHODS: We performed a secondary analysis of data collected prospectively in Project District of Columbia Healthy Outcomes of Pregnancy Education. Our study included 724 African-American women. Self-reported smoking, cotinine levels, and pregnancy outcomes were examined. RESULTS: Some 18% of participants were smokers. Women with salivary cotinine levels greater than 200 ng/ml had infants with lower birth weights and a higher incidence of small-for-gestational-age infants than women with cotinine levels of 200 ng/ml or less. Exact logistic regression analysis revealed that women with salivary cotinine levels greater than 200 ng/ml had a significantly lower incidence of preeclampsia, compared with women with cotinine levels of 200 ng/ml or less, in unadjusted analysis (odds ratio [OR] = 0.16, 95% CI = 0-0.90). After controlling for age, parity, and medical comorbidities, the trend was observed, but the effect was no longer significant (adjusted odds ratio [AOR] = 0.19, 95% CI = 0-1.11). We found no significant differences in preeclampsia rates using lower cutoffs of cotinine exposure. We did not observe a decrease in preeclampsia incidence at low or moderate cotinine levels. DISCUSSION: Women with the highest cotinine levels may have a decreased risk for preeclampsia, although this effect was not significant after controlling for other risk factors.

Pregnancy in Women With Systemic Lupus and Lupus Nephritis.

Pregnancy is an altered immunologic state in which hormonal changes impact the immune system to enable maternal tolerance of the fetus. These hormonal and immunologic changes may affect disease activity in systemic lupus erythematosus. Conversely, lupus nephritis and its complications may adversely impact pregnancy. Systemic lupus erythematosus increases the risk of pre-eclampsia and its complications, including preterm birth and intrauterine growth restriction. Comorbidities such as impaired kidney function and hypertension confer additional risk and complexity. Medications used to treat lupus nephritis may impact the fetus, so therapy needs to be tailored to balance maternal benefit and fetal risk. The diagnosis of lupus nephritis during pregnancy can be difficult, as it shares overlapping features with pre-eclampsia. Kidney biopsy is generally safe in pregnancy, and should be considered if the result will affect management. Here we review the clinical aspects of counseling, diagnosis, and management of lupus nephritis in pregnancy.

Circulating angiogenic factors in singleton vs multiple-gestation pregnancies.

OBJECTIVE: Placental soluble fms-like tyrosine kinase-1 may contribute to the pathogenesis of preeclampsia. Here we describe alterations in serum angiogenic factor levels in women with multiple gestation pregnancies, a major preeclampsia risk factor. STUDY DESIGN: We collected serial serum specimens from 101 pregnant women at high preeclampsia risk between 22 and 36 weeks' gestation. Soluble fms-like tyrosine kinase-1 and placental growth factor were measured by enzyme-linked immunosorbent assay. Women who had preeclampsia or gestational hypertension develop were excluded. RESULTS: Maternal soluble fms-like tyrosine kinase-1 was higher in multiple gestation (n = 20) compared with high-risk singleton (n = 81) pregnancies for each gestational age range examined. Maternal placental growth factor was significantly higher in multiple vs high-risk singletons before 31 weeks' gestation, whereas the soluble fms-like tyrosine kinase-1/placental growth factor ratio was higher in multiple vs high-risk singletons after 27 weeks. CONCLUSION: Alterations in circulating angiogenic factors are present in women with multiple gestations and may contribute to higher preeclampsia risk in this population.

Primary Hyperoxaluria Type 1 with Thrombophilia in Pregnancy: A Case Report.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a mutation in the AGXT gene, resulting in deficiency of the alanineglyoxylate:aminotransferase enzyme. It is characterized by accumulation of oxalate in the kidneys and other organs. CASE PRESENTATION: A Syrian woman with a history of nephrolithiasis and heterozygosity for factor V Leiden and prothrombin gene mutations presented with postpartum renal failure. She required initiation of renal replacement therapy at 14 weeks postpartum. Kidney biopsy showed severe acute and chronic crystalline deposition consistent with oxalate nephropathy. Genetic testing revealed a Gly170Arg mutation in the AGXT gene, confirming the diagnosis of PH1. CONCLUSIONS: The diagnosis of PH should be considered in patients with severe, recurrent calcium oxalate nephrolithiasis. Early treatment with pyridoxine reduces urinary oxalate excretion and can delay progression to end-stage renal disease (ESRD). After ESRD, intensive dialysis is needed to prevent systemic oxalate accumulation and deposition. Combined liver and kidney transplantation is curative. In our patient, we anticipate that liver transplantation will cure both the hyperoxaluria and the hypercoagulable state.

Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.

Preeclampsia, a syndrome affecting 5% of pregnancies, causes substantial maternal and fetal morbidity and mortality. The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1 that fall after delivery. We demonstrate that increased circulating sFlt1 in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PlGF, resulting in endothelial dysfunction in vitro that can be rescued by exogenous VEGF and PlGF. Additionally, VEGF and PlGF cause microvascular relaxation of rat renal arterioles in vitro that is blocked by sFlt1. Finally, administration of sFlt1 to pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis, the classic lesion of preeclampsia. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia.

Circulating angiogenic factors and the risk of preeclampsia.

BACKGROUND: The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. METHODS: We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. RESULTS: During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. CONCLUSIONS: Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia.

Angiogenic factors for the prediction of preeclampsia in high-risk women.

OBJECTIVE: The objective of the study was to evaluate angiogenic factors for the prediction of preeclampsia in high-risk women. STUDY DESIGN: We collected serial serum specimens from 94 women at high preeclampsia risk between 22 and 36 weeks' gestation. Soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay. RESULTS: Mean serum sFlt1 and the sFlt1/PlGF ratio were higher in subjects who developed early-onset (less than 34 weeks) preeclampsia, as compared with subjects without preeclampsia, from 22 weeks gestation onward. In subjects who developed late-onset (34 weeks or later) preeclampsia, sFlt1 was significantly increased after 31 weeks' gestation. The sFlt1/PlGF ratio at 22-26 weeks was highly predictive of early-onset preeclampsia. The within-woman rate of change of the sFlt1/PlGF ratio was predictive of overall preeclampsia risk. CONCLUSIONS: In high-risk women, serum sFlt1 and the sFlt1:PlGF ratio are altered prior to preeclampsia onset and may be predictive of preeclampsia. Larger studies are needed to confirm these findings.

Percutaneous coronary intervention and inpatient mortality in patients with advanced chronic kidney disease presenting with acute coronary syndrome.

Chronic kidney disease (CKD) is an important risk factor for coronary artery disease, yet patients with CKD are less likely to undergo coronary angiography and percutaneous coronary intervention (PCI). We retrospectively analyzed the 2006-2012 National Inpatient Sample Database to examine the temporal trends in coronary angiography and PCI among patients without CKD, with advanced CKD (CKD III-V), and with end-stage renal disease (ESRD) presenting with unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and ST-elevation myocardial infarction (STEMI). A total of 579,747 admissions for NSTE-ACS and 293,950 admissions for STEMI were studied. Patients with NSTE-ACS were less likely to undergo coronary angiography/PCI than those with STEMI, irrespective of CKD. Between 2006 and 2012, performance of PCI saw an uptrend across all CKD groups with NSTE-ACS (no CKD, 29.9%-36.8%; CKD III-V, 18.2%-21.5%; ESRD, 19.8%-27.5%; all Ptrends < 0.01) and STEMI (no CKD, 57.0%-76.0%; CKD III-V, 33.0%-52.6%; ESRD, 29.9%-42.9%; Ptrends < 0.01). Multivariate analyses revealed that PCI was associated with a lower risk of hospital mortality across all degrees of CKD in both NSTE-ACS (adjusted odds ratios: no CKD, 0.44; CKD III-V, 0.48; ESRD, 0.46; P < 0.01) and STEMI (no CKD, 0.35; CKD III-V, 0.50; ESRD, 0.52; P < 0.01). Performance of PCI increased over time among patients presenting with NSTE-ACS and STEMI in the presence of advanced CKD and independently predicted lower in-hospital mortality.

Career interest and perceptions of nephrology: A repeated cross-sectional survey of internal medicine residents.

BACKGROUND: Interest in nephrology careers among internal medicine residents in the United States is declining. Our objective was to assess the impact of the presence of a nephrology fellowship training program on perceptions and career interest in nephrology among internal medicine residents. A secondary objective was to identify commonly endorsed negative perceptions of nephrology among internal medicine residents. METHODS: This was a repeated cross-sectional survey of internal medicine residents before (Group 1) and 3 years after (Group 2) the establishment of nephrology fellowship programs at two institutions. The primary outcome was the percentage of residents indicating nephrology as a career interest in Group 1 vs. Group 2. Secondary outcomes included the frequency that residents agreed with negative statements about nephrology. RESULTS: 131 (80.9%) of 162 residents completed the survey. 19 (14.8%) residents indicated interest in a nephrology career, with 8 (6.3%) indicating nephrology as their first choice. There was no difference in career interest in nephrology between residents who were exposed to nephrology fellows during residency training (Group 2) and residents who were not (Group 1). The most commonly endorsed negative perceptions of nephrology were: nephrology fellows have long hours/burdensome call (36 [28.1%] of residents agreed or strongly agreed), practicing nephrologists must take frequent/difficult call (35 [27.6%] agreed or strongly agreed), and nephrology has few opportunities for procedures (35 [27.3%] agreed or strongly agreed). More residents in Group 2 agreed that nephrology is poorly paid (8.9% in Group 1 vs. 20.8% in Group 2, P = 0.04), whereas more residents in Group 1 agreed that nephrologists must take frequent/difficult call (40.0% in Group 1 vs. 18.1% in Group 2, P = 0.02). CONCLUSIONS: The initiation of a nephrology fellowship program was not associated with an increase in internal medicine residents' interest in nephrology careers. Residents endorsed several negative perceptions of nephrology, which may affect career choice.

Serum sFlt1 concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women.

OBJECTIVE: The purpose of this study was to determine whether serum fms-like tyrosine kinase 1 (sFlt1) concentration during preeclampsia were associated with mid trimester blood pressure, other maternal characteristics, or pregnancy outcomes. STUDY DESIGN: We performed a nested case-control study within the Calcium for Preeclampsia Prevention study cohort. Each woman with preeclampsia (case) was matched to 1 normotensive control. A total of 120 pairs of women was chosen randomly. Serum concentrations of sFlt1 and placental growth factor were measured throughout pregnancy, but before labor and delivery. We focused on data from 40 women with blood specimens that were obtained after the onset of preeclampsia. After logarithmic transformation, we determined mean serum sFlt1 concentrations of all control specimens within gestational age windows during which case specimens had been obtained after the onset of preeclampsia. Within each of these gestational age windows, we computed an upper bound for the control specimens equal to 2 standard deviations above the mean. After the onset of preeclampsia, 16 women with log-transformed serum sFlt1 values greater than the upper bound of the control specimens were considered to have high preeclampsia serum sFlt1 levels. The 24 other women were considered to have low preeclampsia serum sFlt1 levels. RESULTS: Women with high or low concentrations of serum sFlt1 during preeclampsia (arithmetic means, 5746 and 3007 pg/mL, respectively) had similar pregnancy outcomes and similar maternal characteristics, except for blood pressure at Calcium for Preeclampsia Prevention study enrollment. Systolic and diastolic blood pressure at enrollment at 13 to 21 weeks of gestation were significantly higher in the 24 women with low serum sFlt1 concentrations during preeclampsia (systolic blood pressure, 114 mm Hg; diastolic blood pressure, 65 mm Hg) than in the 16 women who had preeclampsia at high serum sFlt1 concentrations (systolic blood pressure, 106 mm Hg; diastolic blood pressure, 59 mm Hg). Blood pressure at 13 to 21 weeks among the women with high preeclampsia serum sFlt1 concentrations was identical to the blood pressure among normotensive control subjects. In linear regression analyses of data from all 40 women, both systolic (P < .0001) and diastolic (P = .014) blood pressures at enrollment were correlated negatively with natural logarithm serum sFlt1 concentration after onset of preeclampsia. CONCLUSION: Women with higher mid trimester blood pressure had preeclampsia at lower serum sFlt1 concentrations. Because higher blood pressure may reflect occult endothelial damage, these observations may explain increased susceptibility to preeclampsia among women with pre-existing vascular disease.

Women, work and childcare: where have we been? Where are we going?

Working mothers who simultaneously manage a job, raise children, and maintain a home may find the endeavor to be physically and emotionally challenging. By means of a case study, this paper explores the impact of work-related injury on one mother's ability to meet the physical demands of childcare and homemaking tasks without jeopardizing her physical recovery or job security. Following a musculoskeletal injury at work, the subject received traditional occupational therapy intervention as well as specific education regarding ergonomic childcare techniques. Her ability to perform routine homemaking and childcare tasks was assessed prior to and following treatment using the ErgoMomics MOMS (Measure of Musculoskeletal Symptoms) survey. The case study suggests that educating mothers in ergonomic techniques related to vocational as well as avocational tasks may be beneficial in helping them manage the dual demands of family life and career. Additional informal interviews were conducted with twelve mothers, ages thirty-five to sixty-eight, in order to frame the case study within a wider historical perspective concerning the role of work in women's lives.