Hospital surgical volume-outcome relationship in caesarean hysterectomy for placenta accreta spectrum.

OBJECTIVE: To examine the association between hospital surgical volume of caesarean hysterectomy and surgical morbidity in women with placenta accreta spectrum (PAS). DESIGN: Population-based retrospective cohort study. SETTING: National Inpatient Sample, January 2016 to December 2018. POPULATION: Six thousand and ten women with PAS who underwent caesarean hysterectomy in 738 centres. METHODS: (1) Comprehensive modelling for relative hospital surgical volume cut-point selection, (2) multinomial regression analysis for characterising hospital surgical volume, and (3) binary logistic regression analysis to examine the volume-outcome relationship. MAIN OUTCOME MEASURES: Surgical morbidity (haemorrhage, coagulopathy, shock, urinary tract injury, and death). RESULTS: The majority of centres had five surgeries over the 3-year period (468 centres, 63.4%) and were grouped as the low-volume group. Surgical morbidity decreased after a relative hospital surgical volume of 25 cases (24 centres, 3.3%) was reached, grouped as the high-volume group. The remaining centres were grouped as the mid-volume group (246 centres, 33.3%). In multivariable analysis, women in the high-volume group were more likely to be Black, have lower median household income, medical comorbidity, previous caesarean delivery, placenta praevia or placenta percreta, and to have undergone surgeries at large urban teaching hospitals compared with those in the low-volume group (all, P < 0.05). After controlling for patient demographics, hospital characteristics and pregnancy factors, performance of caesarean hysterectomy at high-volume centres was associated with a 22% decreased risk of surgical complications compared with surgery at the low-volume centres (adjusted odds ratio 0.78, 95% CI 0.64-0.94). CONCLUSION: Caesarean hysterectomy for PAS is a rare surgical procedure. Higher hospital surgical volume may be associated with improved surgical outcome in PAS. TWEETABLE ABSTRACT: Higher hospital caesarean hysterectomy volume may be associated with improved surgical outcome in PAS.

Outcomes during delivery hospitalisations with inflammatory bowel disease.

OBJECTIVE: To characterise inflammatory bowel disease (IBD) trends and associated risk during delivery hospitalisations. DESIGN: Cross-sectional. SETTING: US delivery hospitalisations. POPULATION: Delivery hospitalisations in the 2000-2018 National Inpatient Sample. METHODS: This study analysed a nationally representative hospital discharge database based on the presence of IBD. Temporal trends in IBD were analysed using joinpoint regression to estimate the average annual percent change (AAPC). IBD severity was characterised by the presence of diagnoses such as penetrating and stricturing disease and history of bowel resection. Risks for adverse outcomes were analysed based on presence of IBD. Poisson regression models were performed with unadjusted and adjusted risk ratios (aRR) as measures of effect. MAIN OUTCOME MEASURE: Prevalence of IBD and associated adverse outcomes. RESULTS: Of 73 109 790 delivery hospitalisations, 89 965 had a diagnosis of IBD. IBD rose from 0.06% in 2000 to 0.21% in 2018 (AAPC 7.3%, 95% CI 6.7-7.9%). Among deliveries with IBD, IBD severity diagnoses increased from 4.1% to 8.1% from 2000 to 2018. In adjusted analysis, IBD was associated with increased risk for preterm delivery (aRR 1.50, 95% CI 1.47-1.53), severe maternal morbidity (aRR 1.93, 95% CI 1.83-2.04), venous thrombo-embolism (aRR 2.76, 95% CI 2.39-3.18) and surgical injury during caesarean delivery hospitalisation (aRR 5.03, 95% CI 4.76-5.31). In the presence of a severe IBD diagnosis, risk was further increased for all adverse outcomes. CONCLUSION: IBD is increasing in the obstetric population and is associated with adverse outcomes. Risk is increased in the presence of a severe IBD diagnosis. TWEETABLE ABSTRACT: Deliveries among women with inflammatory bowel disease are increasing. Disease severity is associated with adverse outcomes.

Minimally invasive surgery for suspected early-stage ovarian cancer; a cost-effectiveness study.

OBJECTIVE: While there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses. DESIGN: Cost-effectiveness study POPULATION: Hypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management. METHODS: The initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings. MAIN OUTCOME MEASURES: The primary outcome was the cost-effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost-effectiveness ratios (ICERs). RESULTS: MIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer-related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses. CONCLUSION: MIS constitutes a cost-effective management strategy for women with suspicious ovarian masses. TWEETABLE ABSTRACT: MIS is a cost-effective management strategy for women with suspicious ovarian masses.

The role of the vaginal microbiome in gynaecological cancer.

Human microbiome research has shown commensal bacteria to be a major factor in both wellness and disease pathogenesis. Interest in the microbiome has recently expanded beyond the gut to include a multitude of other organ systems for which the microbiome may have health implications. Here, we review the role of the vaginal microbiome in health and disease, with a particular focus on gynaecologic malignancies. Further, we suggest that it may be possible to expand the use of probiotics in the treatment of gynaecological cancers. TWEETABLE ABSTRACT: A review of the research to date on the relation between the vaginal microbiome and gynaecological cancers.

Uterine leiomyosarcoma: a review of recent advances in molecular biology, clinical management and outcome.

Uterine leiomyosarcoma (LMS) are rare but aggressive tumours with poor clinical outcomes regardless of stage. Most tumours are identified by histopathology at time of surgery, and pre-operative diagnosis remains a clinical challenge. Management of early-stage LMS relies on surgical resection. Cytotoxic chemotherapy remains the mainstay of therapy for advanced-stage, recurrent or metastatic LMS, and includes single or combination doxorubicin-, ifosfamide- or gemcitabine-based regimens. Recent interest in genetic biomarkers led to developments of targeted therapies for LMS, although more research is needed to understand the molecular complexities underlying LMS to guide the development of novel treatment strategies. TWEETABLE ABSTRACT: The diagnosis and treatment of uterine LMS is challenging. Novel biomarkers offer hope for future therapies.

Serious maternal complications in relation to severe pre-eclampsia: a retrospective cohort study of the impact of hospital volume.

OBJECTIVE: We examined rates of serious maternal complications in relation to severe pre-eclampsia based on the delivering hospital's annualised volume. DESIGN: Retrospective cohort study. POPULATION AND SETTING: Singleton deliveries (n = 25 782 235) in 439 hospitals in the USA. METHODS: Annualised hospital volume was categorised as 25-500, 501-1000, 1001-2000 and >2000. MAIN OUTCOME MEASURES: Rates of in-hospital maternal death and serious maternal complications, including puerperal cerebrovascular disorders, pulmonary oedema, disseminated intravascular coagulation, acute renal, heart and liver failure, sepsis, haemorrhage and intubation in relation to severe pre-eclampsia. We derived adjusted risk ratio (RR) and 95% confidence interval (CI), from hierarchical Poisson regression models. RESULTS: Severe pre-eclampsia was associated with an 8.7-fold (95% CI 7.6, 10.1) risk of composite maternal complications, with similar RRs across levels of hospital volumes. However, compared with hospitals with low annual volume (<2000), maternal mortality rates in relation to severe pre-eclampsia were lower in high volume hospitals. The rates of serious maternal complications were 410.7 per 10 000 to women who delivered in hospitals with a high rate of severe pre-eclampsia (≥2.12%) and 584.8 per 10 000 to women who delivered in hospitals with low severe pre-eclampsia rates (≤0.41; RR 1.75, 95% CI 1.24, 2.45). CONCLUSIONS: While the risks of serious maternal complications in relation to severe pre-eclampsia was similar across hospital delivery volume categories, deaths showed lower rates in large delivery volume hospitals than in smaller volume hospitals. The risk of complications was increased in hospitals with low compared with high severe pre-eclampsia rates. TWEETABLE ABSTRACT: Hospital volume had little impact on the association between severe pre-eclampsia and maternal complications.

Gestational diabetes in the United States: temporal changes in prevalence rates between 1979 and 2010.

OBJECTIVE: To examine age-period-cohort effects on trends in gestational diabetes mellitus (GDM) prevalence in the US, and to evaluate how these trends have affected the rates of stillbirth and large for gestational age (LGA)/macrosomia. DESIGN: Retrospective cohort study. SETTING: USA, 1979-2010. POPULATION: Over 125 million pregnancies (3 337 284 GDM cases) associated with hospitalisations. METHODS: Trends in GDM prevalence were examined via weighted Poisson models to parse out the extent to which GDM trends can be attributed to maternal age, period of delivery, and maternal birth cohort. Multilevel models were used to assess the contribution of population effects to the rate of GDM. Log-linear Poisson regression models were used to estimate the contributions of the increasing GDM rates to changes in the rates of LGA and stillbirth between 1979-81 and 2008-10. MAIN OUTCOME MEASURES: Rates and rate ratios (RRs). RESULTS: Compared with 1979-1980 (0.3%), the rate of GDM has increased to 5.8% in 2008-10, indicating a strong period effect. Substantial age and modest cohort effects were evident. The period effect is partly explained by period trends in body mass index (BMI), race, and maternal smoking. The increasing prevalence of GDM is associated with a 184% (95% CI 180-188%) decline in the rate of LGA/macrosomia and a 0.75% (95% CI 0.74-0.76) increase in the rate of stillbirths for 2008-10, compared with 1979-81. CONCLUSIONS: The temporal increase in GDM can be attributed to period of pregnancy and age. Increasing BMI appears to partially contribute to the GDM increase in the US. TWEETABLE ABSTRACT: The increasing prevalence of GDM can be attributed to period of delivery and increasing maternal age.

Trends in operative vaginal delivery, 2005-2013: a population-based study.

OBJECTIVE: The objectives of this study were to determine temporal trends in forceps and vacuum delivery and factors associated with operative vaginal delivery. DESIGN: Retrospective cohort. SETTING: Population-based study of US birth records. POPULATION: US births from 2005 to 2013. METHODS: This study evaluated forceps and vacuum extraction during vaginal delivery in live-born, non-anomalous singleton gestations from ≥ 36 to < 42 weeks of gestation. The primary outcomes were vacuum, forceps and overall operative delivery. Obstetric, medical and demographic characteristics associated with operative vaginal delivery were analysed. Multivariable logistic regression models were developed to determine factors associated with forceps/vacuum use. RESULTS: A total of 22 598 971 vaginal deliveries between 2005 and 2013 were included in the analysis. In all, 1 083 318 (4.8%) were vacuum-assisted and 237 792 (1.1%) were by forceps. Both vacuum and forceps deliveries decreased over the study period; vacuum deliveries decreased from 5.8% in 2005 to 4.1% in 2013, and forceps deliveries decreased from 1.4% to 0.9% during the same period. The adjusted odds ratio for forceps delivery was 0.70 (95% CI 0.69-0.72) in 2013 with 2005 as a reference. For vacuum delivery the odds ratio was 0.68 (95% CI 0.67-0.69) comparing the same years. CONCLUSION: Forceps and vacuum deliveries decreased during the study period. Low rates of operative delivery pose a challenge for resident education and may limit the degree to which women have access to alternatives to caesarean delivery. Initiatives that allow future generations of obstetricians to develop expertise in performing operative deliveries in the setting of decreased volume are an urgent resident education priority. TWEETABLE ABSTRACT: Forceps and vacuum delivery decreased significantly in the USA from 2005 to 2013.

Hospital variation in maternal complications following caesarean delivery in the United States: 2006-2012.

OBJECTIVE: To assess hospital variability in and patient and hospital factors associated with caesarean delivery (CD) complications. STUDY DESIGN: Population-based cohort. SETTING: United States delivery admissions. POPULATION: Women who underwent a CD between 2006 and 2012. METHODS: Hospital-specific random-effects log-linear regression models were developed to account for patient, obstetric, and hospital risk factors related to a composite complication outcome including infection, haemorrhage, surgical complications and prolonged hospital stay. Between-hospital variability in rates of CD complications was also estimated. MAIN OUTCOME MEASURE: Composite complication rate. RESULTS: Among 1 339 397 women who underwent CD in 457 hospitals, 6.4% (n = 85 838) experienced a complication. The most frequent complications were haemorrhage, transfusion, length of stay >7 days, and endometritis. Complications were strongly associated with the presence of obstetric factors and pre-existing medical conditions. Complication rates were 54% higher among black (8.8%) than white (5.7%) women (P < 0.001), and were more common in teaching (8.1%) than non-teaching (5.4%) hospitals (P < 0.001). In an adjusted model, the mean complication rate was 6.7%. A small proportion of hospitals (4.8%) had a complication rate greater than twice the mean (≥13.4%). Complications were strongly associated with the presence of obstetrical factors and pre-existing medical conditions. CONCLUSIONS: CD complication rates are strongly associated with patient and obstetric factors. While CD complication rates may be a quality metric of limited utility given the low rate of complications across most hospitals, a small number of hospitals demonstrate particularly high rates of complications. Review of CD complication rates may be an important aspect of quality assurance processes for these centres. TWEETABLE ABSTRACT: A small number of hospitals demonstrate particularly high rates of caesarean complications.

Measurement and validation of frailty as a predictor of outcomes in women undergoing major gynaecological surgery.

OBJECTIVE: Frailty is the loss of physical or mental reserve that impairs function, often in the absence of a defined comorbidity. Our aim was to determine whether a modified frailty index (mFI) correlates with morbidity and mortality in patients undergoing hysterectomy. DESIGN: Retrospective cohort study. SETTING: Hospitals across the USA participating in the National Surgical Quality Improvement Program (NSQIP). SAMPLE: Patients who underwent hysterectomy from 2008 to 2012. METHODS: An mFI was calculated using 11 variables in NSQIP. The associations between mFI and morbidity and mortality were assessed. Model fit statistics (c-statistics) were utilised to evaluate the ability of mFI to distinguish outcomes. MAIN OUTCOME MEASURE: Wound infection, severe complications and mortality. RESULTS: A total of 66 105 patients were identified. Wound complications increased from 2.4% in patients with an mFI of zero to 4.8% in those with mFI ≥ 0.5 (P < 0.0001). Similarly, severe complications increased from 0.98% to 7.3% (P < 0.0001), overall complications rose from 3.7% to 14.5% (P < 0.0001) and mortality increased from 0.06% to 3.2% (P < 0.0001) for patients with a frailty index of zero compared with those with an index of ≥ 0.5. Versus chance, the goodness-of-fit c-statistics suggested that mFI increases the ability to detect wound complications by 11.4%, severe complications by 22.0% and overall complications by 11.0%. CONCLUSIONS: The mFI is easily reproducible from routinely collected clinical data and predictive of outcomes in patients undergoing hysterectomy. Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery. TWEETABLE ABSTRACT: Frailty may be useful in the preoperative risk assessment of women undergoing gynaecological surgery.

Surgical management of placenta accreta: to leave or remove the placenta?

Abnromalities of placentation, including placenta accreta, represent a major source of morbidity and mortality among women. Traditional management consists of peripartum hysterectomy at the time of delivery, although more conservative treatments have also been developed recently. In this review we describe the available literature describing the operative approach and considerations for management of women with placenta accreta.

Influence of health insurance, hospital factors and physician volume on receipt of immediate post-mastectomy reconstruction in women with invasive and non-invasive breast cancer.

For women with breast cancer who undergo mastectomy, immediate breast reconstruction (IR) offers a cosmetic and psychological advantage. We evaluated the association between demographic, hospital, surgeon and insurance factors and receipt of IR. We conducted a retrospective hospital-based analysis with the Perspective database. Women who underwent a mastectomy for invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS) from 2000 to 2010 were included. Logistic regression analysis was used to determine factors predictive of IR. Analyses were stratified by age (<50 vs. ≥ 50) and IBC versus DCIS. Of the 108,992 women with IBC who underwent mastectomy, 30,859 (28.3 %) underwent IR, as compared to 6,501 (44.2 %) of the 14,710 women with DCIS who underwent mastectomy underwent IR. In a multivariable model for IBC, increasing age, black race, being married, rural location, and increased comorbidities were associated with decreased IR. Odds ratios (OR) of IR increased with commercial insurance (OR 3.38) and Medicare (OR 1.66) insurance (vs. self-pay), high surgeon-volume (OR 1.19), high hospital-volume (OR 2.24), and large hospital size (OR 1.20). The results were identical for DCIS, and by age category. The absolute difference between the proportion of patients who received IR with commercial insurance compared to other insurance, increased over time. Immediate in-hospital complication rates were higher for flap reconstruction compared to implant or no reconstruction (15.2, 4.0, and 6.1 %, respectively, P < .0001). IR has increased significantly over time; however, modifiable factors such as insurance status, hospital size, hospital location, and physician volume strongly predict IR. Public policy should ensure that access to reconstructive surgery is universally available.

The urban homeless: estimating composition and size.

Although homelessness has been recognized as a serious and growing urban social problem, scientifically acceptable methods for estimating the composition and size of the homeless population have been lacking. A new research approach to estimating the size and composition of undomiciled urban populations is presented, and its utility is illustrated through a description of the literal homeless of Chicago. The homeless in the Chicago sample are unaffiliated persons living in extreme poverty, with high levels of physical and mental disability. Homelessness is interpreted as a manifestation of extreme poverty among persons without families in housing markets with declining stocks of inexpensive dwelling units suitable for single persons.

Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: a multi-institutional review.

OBJECTIVE: To assess the role of surgical staging, adjuvant therapy, and cytoreduction in uterine clear cell carcinoma (UCCC). METHODS: A retrospective review was conducted at 2 major gynecologic cancer centers of all primary UCCC between 1982 and 2004. RESULTS: UCCC was confirmed in 99 patients. The 5-year overall survival (OS) was 79%, 77%, 47%, and 21% for stages I-IV respectively. 69 patients had no gross evidence of extra-uterine disease, but 36 (52%) were upstaged at surgery. For those 22 patients with stages I and II disease who had a systematic lymphadenectomy (LND) (> 20 lymph nodes), no lymphatic (LF), peritoneal (PF), or hematological (HF) failures were noted. Radiation (RT) improved PFS (67 vs. 36%, p=0.02), and reduced pelvic sidewall recurrences (18 vs. 53%, p=0.04) and vaginal failures (VF) (7 vs. 35%, p=0.04) for 45 patients at risk for LF (positive nodes or suboptimal LND). 39 patients with stages IIIC and IV disease were separately analyzed. Patients with no visible residual disease after cytoreduction had a significant improvement in median PFS (17 vs. 7 months, p<0.001), and OS (40 vs. 18 months, p=0.02) compared to patients with any residual disease after surgery. CONCLUSION: Comprehensive surgical staging with a systematic LND is essential to accurately define early stage UCCC. Vaginal brachytherapy may be adequate adjuvant therapy for stages I and II UCCC confirmed by systematic LND. Patients at risk for LF appear to benefit from pelvic RT. An effort at cytoreduction to no visible residual disease should be made in advanced UCCC when feasible.

Prognostic factors associated with response in platinum retreatment of platinum-resistant ovarian cancer.

The goal of this study was to determine the factors associated with response to platinum retreatment in patients with platinum-resistant ovarian cancer. A review of patients with epithelial ovarian cancer retreated with cisplatin or carboplatin between 2002 and 2004 was performed. The platinum-free interval (PFI) and treatment-free interval (TFI) were determined for each patient. Response was based on serial CA125 levels using a modification of the Rustin criteria. Patients with clinical benefit ([CB] those who attained at least stable disease) were compared to patients with disease progression (PD). An analysis was performed to determine factors associated with CB in platinum-resistant patients retreated with platinum. Of 48 patients identified, 37 were evaluable included in this analysis. CB was observed in 27 (73%) while disease progression was noted in 10 (27%) women. The PFI was longer in those women who achieved CB (12.3 vs 6.9 months; P = 0.02). The TFI was 7.1 months for patients benefited from platinum retreatment vs 3.5 months for those with disease progression (P = 0.06). There was no statistically significant difference in the number of cytotoxic agents between the time of platinum retreatment and the prior platinum regimen (2 vs 1.5 months; P = 0.61). A prolonged PFI was associated with an improved chance of achieving CB with platinum retreatment. There was no association between the response to platinum retreatment and the number of intervening cytotoxic agents utilized. Further prospective study is warranted to define the optimal timing of platinum retreatment.

A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer.

While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3-5 toxicities occurred in 15 (24%) patients, including grade 3-4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3-5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy.

Identification of sites on epidermal growth factor receptors which are phosphorylated by pp60src in vitro.

The Epidermal Growth Factor Receptor (EGF-R) becomes constitutively tyrosine phosphorylated on two novel sites in v-Src transformed cells, and these phosphorylations are associated with enhanced signaling activity [1]. To determine whether Src could directly phosphorylate these sites, we have examined the ability of the Src kinase to phosphorylate both wild-type and kinase-defective EGF-Rs in vitro. Although purified Src could phosphorylate EGF-Rs, the pattern of phosphorylation sites was not identical to what was previously found in vivo [1]: Src in vitro directly phosphorylated EGF-Rs on one autophosphorylation site (Tyr 1173) which was not a site of re-induced in vivo phosphorylation, suggesting the in vivo inaccessibility of this site. One Src-specific in vitro phosphorylation site (Tyr 03) appeared to correspond to one of the in vivo Src-induced sites (sPY2), but the other Src-specific in vivo site (sPY1) was not significantly phosphorylated in vitro, raising the possibility of a Src-induced tyrosine kinase cascade. The ability of Src to phosphorylate the EGF-R is consistent with the suggestion that the receptor can function as a kinase substrate independent of its intrinsic enzymatic activity, as implied by recent studies on signaling by kinase-defective EGF-Rs.

Serum folate and cardiovascular disease mortality among US men and women.

BACKGROUND: Folate has been linked to cardiovascular disease (CVD) through its role in homocysteine metabolism. OBJECTIVE: To assess the relationship between serum folate and CVD mortality. DESIGN: In this prospective study, serum folate concentrations were measured on a subset of adults during the Second National Health and Nutrition Examination Survey (1976-1980) and vital status ascertained after 12 to 16 years. SETTING AND PATIENTS: A national probability sample consisting of 689 adults who were 30 to 75 years of age and did not have a history of CVD at baseline. MAIN OUTCOME MEASURE: Vital status was determined by searching national databases that contained information about US decedents. RESULTS: The associations between serum folate and CVD and all-cause mortality differed by diabetes status (P =.04 and P =.03, respectively). Participants without diabetes in the lowest compared with the highest serum folate tertile had more than twice the risk of CVD mortality after adjustment for age and sex (relative risk [RR], 2.64; 95% confidence interval [CI], 1.15-6.09). This increased risk for participants in the lowest tertile was attenuated after adjustment for CVD risk factors (RR, 2.28; 95% CI, 0.96-5.40). Serum folate tertiles were not significantly associated with total mortality, although the age- and sex-adjusted risk was increased for participants in the lowest compared with highest tertile (RR, 1.74; 95% CI, 0.96-3.15). Risk estimates for participants with diabetes were unstable because of the small sample size (n = 52). CONCLUSION: These data suggest that low serum folate concentrations are associated with an increased risk of CVD mortality among adults who do not have diabetes. Arch Intern Med. 2000;160:3258-3262.