Ora Paltiel

Long-term mortality after preeclampsia

Background: Many believe that preeclampsia is not associated with future morbidity or mortality. We sought to investigate the long-term risk of mortality in women with preeclampsia, focusing on those known to be subsequently normotensive. Study Design: We ascertained deaths during 24–36 years’ follow-up in a cohort of 37,061 women who delivered in Jerusalem in 1964–1976, including 1,070 women with preeclampsia. We used Cox proportional hazard models to estimate the risk of mortality associated with preeclampsia while controlling for the womans age and education, history of diabetes, heart disease and low birth weight birth, the husbands social class, and the calendar year at the start of follow-up. Results: Compared with women who were not diagnosed with preeclampsia, the relative risk of death after preeclampsia was 2.1 (95% confidence interval = 1.8–2.5). Deaths from cardiovascular disease contributed most strongly to this increase. Among women with preeclampsia who had subsequent births without preeclampsia, the excess risk of mortality became manifest only after 20 years. Conclusions: These findings, together with other recent cohort studies, define preeclampsia as a risk marker for mortality from cardiovascular disease. They suggest that the observation of a normal blood pressure after preeclampsia should not discourage the search for other cardiovascular risk factors or abrogate the need for other preventive measures.

Human menopausal gonadotropin and the risk of epithelial ovarian cancer

OBJECTIVE To determine whether women with epithelial ovarian cancer are more likely to have been exposed to fertility drugs, and in particular hMG, than healthy population controls. DESIGN A nationwide case-control study. PATIENTS Two hundred living women 36 to 64 years of age, with a histologically confirmed diagnosis of primary invasive or borderline epithelial ovarian cancer that was first diagnosed and reported to the Israel Cancer Registry between January 1, 1990 and September 1, 1993 were enrolled. There were 164 (82%) invasive and 36 (18%) borderline epithelial ovarian tumors among the 200 cases. The controls were 408 women from the same dialing areas selected by random digit dialing. Cases and controls were interviewed using a standard questionnaire. A multivariate logistic model was used to assess the association of fertility drug use and ovarian cancer, controlling for variables found to be statistically associated with this outcome on univariate analysis. RESULTS Twenty-four women with epithelial ovarian cancer (12%) and 29 healthy controls (7.1%) reported that they had used any fertility drug (adjusted odds ratio [OR] 1.31; 95% confidence interval [CI] 0.63 to 2.74). Among cases and controls, respectively, 22 and 24 reported that they had used hMG alone or in combination with clomiphene citrate (adjusted OR 1.42, 95% CI 0.65 to 3.12), and 11 and 6 reported that they had used hMG alone (adjusted OR 3.19, (95% CI 0.86 to 11.82). The risk was increased particularly in the subgroup of women with borderline ovarian tumors who had used hMG (adjusted OR 9.38, 95% CI 1.66 to 52.08). CONCLUSIONS We conclude that the use of ovulation induction agents, in particular hMG, may increase the risk of epithelial ovarian tumors.

Paternal age and spontaneous abortion.

OBJECTIVE: To evaluate the influence of paternal age upon spontaneous abortion. METHODS: This case–control study of 13,865 women draws on data from womens antenatal or postpartum interviews in the Jerusalem Perinatal Study, a population-based cohort derived from 92,408 births in 1964–1976. Case women (n=1,506) reported spontaneous abortion in the pregnancy preceding the interview; they were compared with women reporting live births in their previous pregnancy (n=12,359). Logistic regression was used to adjust for maternal age, maternal diabetes, maternal smoking, history of spontaneous abortions before the index pregnancy, parity at interview, and interval between the index pregnancy and the interview. RESULTS: The adjusted odds ratio for spontaneous abortion was 0.59 (95% confidence interval 0.45–0.76, P< .0001) for pregnancies conceived from fathers aged younger than 25 years compared with those from fathers aged 25–29 years. For fathers age 40 years or older the odds ratio for spontaneous abortion was 1.6 (95% confidence interval 1.2–2.0, P=.0003) when compared with the same reference group. CONCLUSION: Increasing paternal age is significantly associated with spontaneous abortion, independent of maternal age and multiple other factors. LEVEL OF EVIDENCE: II-2

Etiologic Heterogeneity Among Non-Hodgkin Lymphoma Subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

BACKGROUND Non-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes. METHODS We pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE). RESULTS Risks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. CONCLUSIONS Using a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.

Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: A critical review of the literature

The purpose of our study was to review the evidence for the efficacy of surveillance for early detection, bilateral prophylactic mastectomy, prophylactic oophorectomy and chemoprevention in preventing breast cancer and improving survival of BRCA1 or BRCA2 carriers. A critical review of journal articles published between 1998 and 2004 identified by searches of MEDLINE, PubMed and references of retrieved articles was undertaken. None of the current evidence is based on randomized studies. The efficacy of surveillance for early detection of breast cancer among BRCA1 or BRCA2 carriers is not yet established. Screening with clinical breast examination and mammography showed lower sensitivity in BRCA1 or BRCA2 carriers than in the general population. Screening with MRI might offer higher sensitivity rates than mammography. Prophylactic mastectomy was shown to significantly reduce the risk of breast cancer by 89.5–100%. However, of all strategies reviewed, mastectomy was the least acceptable to women at high risk. Tamoxifen use was associated with breast cancer prevention among BRCA2 carriers (RR=0.38, 95%CI: 0.06–1.56). In BRCA1 or BRCA2 carriers with breast cancer, tamoxifen use was associated with the prevention of secondary breast cancer (OR= 0.50, 95% CI: 0.28–0.89). Prophylactic oophorectomy was associated with hazard ratios for breast cancer of 0.47 (95%CI:0.29–0.77) and 0.32 (95%CI: 0.08–1.20), in retrospective and short follow‐up prospective cohort studies, respectively. There is a pressing need for more studies in order to determine which of the 4 strategies alone, or in combination, is the most effective for the prevention of breast cancer and for the improvement of survival of BRCA mutation carriers.

Cancer Risk After Exposure to Treatments for Ovulation Induction

Uncertainty continues as to whether treatments for ovulation induction are associated with increased risk of cancer. The authors conducted a long-term population-based historical cohort study of parous women. A total of 15,030 women in the Jerusalem Perinatal Study who gave birth in 1974-1976 participated in a postpartum survey. Cancer incidence through 2004 was analyzed using Coxs proportional hazards models, controlling for age and other covariates. Women who used drugs to induce ovulation (n = 567) had increased risks of cancer at any site (multivariate hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.74). An increased risk of uterine cancer was found among women treated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28, 8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34). No association was noted between use of ovulation-inducing agents and ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42). Ovulation induction was associated with a borderline-significant increased risk of breast cancer (multivariate HR = 1.42, 95% CI: 0.99, 2.05). Increased risks were also observed for malignant melanoma and non-Hodgkin lymphoma. These associations appeared stronger among women who waited more than 1 year to conceive. Additional follow-up studies assessing these associations by drug type, dosage, and duration are needed.

Ischemic hepatitis: Clinical and laboratory observations of 34 patients

Ischemic hepatitis, a relatively infrequent disorder occurring in 0.16% to 0.50% of patients admitted to medical intensive care units, often follows episodes of hypotension or acute heart failure. Investigating the clinical characteristics of patients with ischemic hepatitis may add to our understanding of the pathogenesis and significance of this syndrome. We therefore conducted a retrospective analysis of 34 patients to examine the possible contribution of the various baseline characteristics to the severity of the hepatic damage. In all patients liver disease was unexpected and in some, liver dysfunction dominated the clinical picture. All patients had high serum glutamic pyruvic transaminase (SGPT) and lactic dehydrogenase (LDH) levels (mean +/- SE, 2073 +/- 255 international units and 6085 +/- 748 international units, respectively). The mean SGPT/LDH ratio was 0.34. Most patients had coagulopathy with a prolonged prothrombin time (mean +/- SE, 5.86 +/- 1.37 international normalized ratio [INR]). The most common diagnosis on admission was respiratory distress secondary to various causes. Before the development of the hepatic dysfunction, respiratory failure and hypoxemia were observed in 68% of the patients, whereas hypotension was observed in only 38%. More than 90% of the patients had three or more associated comorbid conditions. The most frequent of these were left heart failure (88.2%), right heart failure (67.6%), chronic obstructive lung disease (58.8%), and chronic renal failure (55.9%). During the acute episode, more than 90% of the patients had transient deterioration of their renal functions. Hypoglycemia was noted in 11 patients (32.4%), and the glucose level was inversely correlated with the SGPT level (r = -0.43, p = 0.01). Stepwise multiple regression analysis showed that left heart failure, systolic blood pressure lower than 90 mm Hg, and female gender, together, accounted for 34% of the variance of the peak SGPT levels (p = 0.002). Fourteen (41.2%) patients died during the 3-month follow-up period, but none from the hepatic injury. None of the clinical or laboratory parameters measured predicted mortality. Clearly, ischemic hepatitis is associated with a high risk of death. The characteristic patients are those with multiple underlying systemic diseases and conditions, especially those with left heart failure. Liver function test results and levels of liver enzymes should be monitored in these patients, particularly when they are admitted for respiratory deterioration and episodes of hypotension.

Risk Factors for Central Venous Catheter Thrombotic Complications in Children and Adolescents With Cancer

The use of central venous catheters (CVCs) has greatly improved the quality of care in children with cancer, yet these catheters may cause serious infectious and thrombotic complications. The aim of this prospective registry study was to assess the host and CVC‐related risk factors for CVC‐created thrombotic complications.

Chest radiographs in the emergency department: is the radiologist really necessary?

Background: The chest radiograph is considered one of the most complex imaging modalities to interpret. Several studies have evaluated radiograph interpretation in the emergency department, and considerable disagreement among clinical physicians and expert radiologists has been observed in the reading of chest films. The interpretation of chest radiographs by emergency department physicians was compared with senior radiologists in discharged patients, and misinterpretations assessed in relation to the physician’s level of training. Methods: Radiological descriptions of 509 chest radiographs of 507 patients, aged 16–98 years who were discharged from the emergency department, were prospectively reviewed. Missed findings were recorded with regard to the physician’s level of training and experience. The effects of misinterpretations on discharge recommendations were also investigated. Statistical assessment was conducted using the χ2 test. Interobserver agreement was also tested by the κ coefficient. Results: The sensitivity for detecting different abnormalities in the radiographs ranged from 20% to 64.9% and specificity from 94.9% to 98.7%. Despite the low sensitivities found, there were relatively few clinical implications of the “missed” findings since they were either of a minor nature or appropriate follow up was prescribed. The overall interobserver reliability, assessed by the κ coefficient, was 0.40 (95% confidence interval 0.35 to 0.46). These findings did not change significantly by emergency department physician’s level of training. Conclusions: Emergency department physicians frequently miss specific radiographic abnormalities and there is considerable discrepancy between their interpretations and those of trained radiologists. These findings highlight the importance of routine evaluation of chest radiographs by a well trained radiologist and emphasise the need for improving interpretive skills among emergency department physicians.

Is prolonged immobilization a risk factor for symptomatic venous thromboembolism in elderly bedridden patients? Results of a historical-cohort study

Prolonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinically apparent VTE, we performed a historical-cohort study of nursing home residents during a ten-year period. Data concerning patients mobility and incidence of overt deep vein thrombosis or pulmonary embolism were registered. The mean resident age was 85+/-8.4 years. Eighteen mobile and eight immobile patients were diagnosed with clinically significant thromboembolic events, during 1137 and 573 patient-years of follow up, respectively. The incidence of venous thromboembolic events was similar in both chronically immobilized and mobile patient groups, 13.9 and 15.8 per thousand patient years, respectively (p=0.77). The rate ratio for having a VTE event in the immobilized patient group as compared with the mobile group was 0.88 (95% Confidence Interval (CI) 0.33 to 2.13). When taking into account baseline characteristics, risk factors and death rates by various causes, no differences were found between the two groups. In conclusion, chronically immobile bedridden patients are no more prone to clinically overt venous thromboembolic events than institutionalized mobile patients. Until further studies are performed concerning the impact of very prolonged immobilization on the risk of VTE, there is no evidence to support primary prevention after the first three months of immobilization. Evidence for efficacy or cost effectiveness beyond this early period is not available.