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ABSTRACT: Secondary malignancies are well established complication in long-term survivors after allogeneic stem-cell transplantation (alloSCT) with myeloablative conditioning (MAC). Fludarabine-based reduced-intensity (RIC) and reduced-toxicity (RTC) regimens are increasingly used in the last decade, however, due to limited long-term follow-up, there is no data on secondary malignancies in this setting. The records of 931 consecutive patients given alloSCT with MAC (n=257), RIC (n=449) or RTC (n=225), in a single institution over a 13-year period, were reviewed. Twenty-seven patients had secondary malignancy, diagnosed a median of 43 months (7 months-11.5 years) after SCT. The 10-year cumulative incidence was 5.6% (95%CI, 3.6-8.7), twice the expected rate in matched normal population. The incidence was 1.7, 7.4, and 5.7% after MAC, RIC and RTC, respectively (P=0.02). Multivariate analysis identified fludarabine-based conditioning (HR 3.5, P=0.05), moderate-severe chronic graft-versus-host disease (HR 2.8, P=0.01) and diagnosis of chronic myeloproliferative or non-malignant disease (HR 0.2, P=0.04) as risk-factors for secondary malignancy. The related 10-year mortality rate was 2.4% (95%CI, 1.0-5.4). In conclusion, the risk of secondary malignancies is not reduced and is even possibly increased in the era of fludarabine-based RIC/RTC. Patients and physicians should be aware of this association and life-long cancer screening is required for all transplant survivors.Leukemia accepted article preview online, 17 October 2012; doi:10.1038/leu.2012.299.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2012; · 8.30 Impact Factor
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ABSTRACT: In a preliminary report, we found an association between hyperinsulinemia in the basal (fasting) state and the development of diabetes.
The current analysis further explored the long term link between basal hyperinsulinemia and conversion to dysglycemia.
This is a prospective study with up to 24 years of follow-up of 515 normoglycemic individuals (mean age at follow up = 70.3 ± 7.0; range 58-94) of an Israeli cohort. Fasting glucose and insulin were measured, and dysglycemia was defined as fasting glucose > 100 mg/dL.
At the end of the follow-up period, almost half had progressed to dysglycemia. Male sex and elevated baseline levels of basal insulin, body mass index, blood glucose and blood pressure each favoured progression to dysglycemia over the subsequent two decades. A multivariate logistic regression model identified basal hyperinsulinemia as the strongest predictor for progression to dysglycemia (odds ratio = 1.79; 95% confidence interval 1.12-2.88), while controlling for ethnicity, blood pressure, fasting glucose, male sex, body mass index and age.
Basal hyperinsulinemia in normoglycemic adults constitutes an independent risk factor for metabolic deterioration to dysglycemia over adulthood, and may help to identify apparently healthy subjects at increased risk for diabetes. Copyright © 2012 John Wiley & Sons, Ltd.
Diabetes/Metabolism Research and Reviews 08/2012; 28(7):618-24. · 3.37 Impact Factor
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ABSTRACT: To study the age at presentation and factors associated with adult-onset diabetes (≥ 20 years) among Arabs and Jews in Israel.
Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (κ = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model.
The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43.
Arabs in Israel are at greater risk for adult-onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated.
Diabetic Medicine 11/2011; 29(6):748-54. · 2.90 Impact Factor
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E Cardis,
B K Armstrong,
J D Bowman,
G G Giles,
M Hours,
D Krewski,
M McBride,
M E Parent,
S Sadetzki,
A Woodward,
J Brown, A Chetrit,
J Figuerola,
C Hoffmann,
A Jarus-Hakak,
L Montestruq,
L Nadon,
L Richardson,
R Villegas,
M Vrijheid
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ABSTRACT: The objective of this study was to examine the associations of brain tumours with radio frequency (RF) fields from mobile phones.
Patients with brain tumour from the Australian, Canadian, French, Israeli and New Zealand components of the Interphone Study, whose tumours were localised by neuroradiologists, were analysed. Controls were matched on age, sex and region and allocated the 'tumour location' of their matched case. Analyses included 553 glioma and 676 meningioma cases and 1762 and 1911 controls, respectively. RF dose was estimated as total cumulative specific energy (TCSE; J/kg) absorbed at the tumour's estimated centre taking into account multiple RF exposure determinants.
ORs with ever having been a regular mobile phone user were 0.93 (95% CI 0.73 to 1.18) for glioma and 0.80 (95% CI 0.66 to 0.96) for meningioma. ORs for glioma were below 1 in the first four quintiles of TCSE but above 1 in the highest quintile, 1.35 (95% CI 0.96 to 1.90). The OR increased with increasing TCSE 7+ years before diagnosis (p-trend 0.01; OR 1.91, 95% CI 1.05 to 3.47 in the highest quintile). A complementary analysis in which 44 glioma and 135 meningioma cases in the most exposed area of the brain were compared with gliomas and meningiomas located elsewhere in the brain showed increased ORs for tumours in the most exposed part of the brain in those with 10+ years of mobile phone use (OR 2.80, 95% CI 1.13 to 6.94 for glioma). Patterns for meningioma were similar, but ORs were lower, many below 1.0.
There were suggestions of an increased risk of glioma in long-term mobile phone users with high RF exposure and of similar, but apparently much smaller, increases in meningioma risk. The uncertainty of these results requires that they be replicated before a causal interpretation can be made.
Occupational and environmental medicine 06/2011; 68(9):631-40. · 3.64 Impact Factor
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E. Cardis,
I. Deltour,
M. Vrijheid,
E. Combalot,
M. Moissonnier,
H. Tardy,
B. Armstrong,
G. Giles,
J. Brown,
J. Siemiatycki, [......],
K. G. Blaasaas,
L. Klaeboe,
M. Feychting,
S. Loenn,
A. Ahlbom,
P. A. McKinney,
S. J. Hepworth,
K. R. Muir,
A. J. Swerdlow,
M. J. Schoemaker
International Journal of Epidemiology 01/2010; 39(3):675. · 6.41 Impact Factor
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E. Cardis,
I. Deltour,
M. Vrijheid,
E. Combalot,
M. Moissonnier,
H. Tardy,
B. Armstrong,
G. Giles,
J. Brown,
J. Siemiatycki, [......],
K. G. Blaasaas,
L. Klaeboe,
M. Feychting,
S. Loenn,
A. Ahlbom,
P. A. McKinney,
S. J. Hepworth,
K. R. Muir,
A. J. Swerdlow,
M. J. Schoemaker
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ABSTRACT: Methods An interview-based case-control study with 2708 glioma and 2409 meningioma cases and matched controls was conducted in 13 countries using a common protocol. Results A reduced odds ratio (OR) related to ever having been a regular mobile phone user was seen for glioma [OR 0.81; 95% confidence interval (CI) 0.70-0.94] and meningioma (OR 0.79; 95% CI 0.68-0.91), possibly reflecting participation bias or other methodological limitations. No elevated OR was observed >= 10 years after first phone use (glioma: OR 0.98; 95% CI 0.76-1.26; meningioma: OR 0.83; 95% CI 0.61-1.14). ORs were < 1.0 for all deciles of lifetime number of phone calls and nine deciles of cumulative call time. In the 10th decile of recalled cumulative call time, >= 1640 h, the OR was 1.40 (95% CI 1.03-1.89) for glioma, and 1.15 (95% CI 0.81-1.62) for meningioma; but there are implausible values of reported use in this group. ORs for glioma tended to be greater in the temporal lobe than in other lobes of the brain, but the CIs around the lobe-specific estimates were wide. ORs for glioma tended to be greater in subjects who reported usual phone use on the same side of the head as their tumour than on the opposite side. Conclusions Overall, no increase in risk of glioma or meningioma was observed with use of mobile phones. There were suggestions of an increased risk of glioma at the highest exposure levels, but biases and error prevent a causal interpretation. The possible effects of long-term heavy use of mobile phones require further investigation.
International Journal of Epidemiology 01/2010; 39(3):675-694. · 6.41 Impact Factor
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M Vrijheid,
S Mann,
P Vecchia,
J Wiart,
M Taki,
L Ardoino,
B K Armstrong,
A Auvinen,
D Bédard,
G Berg-Beckhoff, [......],
S Lagorio,
S Lönn,
M McBride,
L Montestrucq,
R C Parslow,
S Sadetzki,
J Schüz,
T Tynes,
A Woodward,
E Cardis
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ABSTRACT: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study.
More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call.
Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas.
Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.
Occupational and environmental medicine 06/2009; 66(10):664-71. · 3.64 Impact Factor
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ABSTRACT: In order to allot an ovarian malignancy to FIGO Stage I, in addition to abdominal exploration and the basic operation, it is also necessary to do peritoneal washings for cytological examination, random peritoneal biopsies (including diaphragmatic assessment) and omental and retroperitoneal lymph node assessment.
The aim of the study was to assess the accuracy of surgical staging of ovarian carcinoma classified as Stage I in Israel.
Included were all patients with histologically confirmed epithelial ovarian carcinoma (EOC) classified as Stage I in a data base of a nationwide incidence case control epidemiological study of ovarian carcinoma conducted in Israeli Jewish women during the period 1994-1999. Surgical staging data of these patients were retrieved from pathological reports, and from clinical records when available.
A total of 182 EOC patients were classified as Stage I. About 86% of the patients underwent hysterectomy and bilateral salpingo-oophorectomy. The most commonly performed staging procedure was omental assessment (85.2%) while peritoneal biopsy was the least common one (34.1%). In 17 (9.3%) of the patients none of the staging procedures were done and only 34 (18.7%) had optimal staging.
Although the data are from a decade ago, they seem to indicate the need for an increased awareness of the necessity for accurate surgical staging of tumors apparently confined to the ovaries since it can identify a group of patients who require surgical therapy alone and who can be spared the complications, inconvenience and cost of adjuvant chemotherapy.
European journal of gynaecological oncology 01/2009; 30(4):375-8. · 0.47 Impact Factor
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ABSTRACT: Family history (FH) scores are used for estimating the familial risk (FR), i.e. the level of risk for a particular disease among members of that family. An FH score is created from reports about the disease status of the relatives in each family. The most commonly used score is the dichotomous score (positive when at least one relative is affected), which does not consider the family size, number of affected relatives nor each relative's risk factor profile. Authors have proposed many other FH scores that overcome these deficiencies by using external expected risks adjusted for important risk factors. We consider the use of FH scores in studies, which investigate risk factors for a disease and where family risk is considered as a confounder, and examine through simulations the performance of a variety of FH scores in controlling the FR status. We also examine performance in predicting true FR status. For both criteria, only small differences were found between most of the FH scores, although the dichotomous score performed the poorest. Since the proportion score (the proportion of first-degree relatives of the index who have the disease) is the simplest to calculate, use of this score seems to be justified.
Statistics in Medicine 07/2007; 26(14):2785-98. · 1.88 Impact Factor
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J Danesh,
S Erqou,
M Walker,
S G Thompson,
R Tipping,
C Ford,
S Pressel,
G Walldius,
I Jungner,
A R Folsom, [......],
L Pennells,
P Perry,
K Ray,
N Sarwar,
M Scherman,
A Thompson,
S Watson,
F Wensley,
I R White,
A M Wood
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ABSTRACT: Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
European Journal of Epidemiology 02/2007; 22(12):839-69. · 4.71 Impact Factor
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M Vrijheid,
E Cardis,
B K Armstrong,
A Auvinen,
G Berg,
K G Blaasaas,
J Brown,
M Carroll, A Chetrit,
H C Christensen, [......],
S Lönn,
P A McKinney,
L Montestrucq,
R C Parslow,
L Richardson,
S Sadetzki,
T Salminen,
J Schüz,
T Tynes,
A Woodward
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ABSTRACT: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use.
Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls.
Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use.
Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.
Occupational and environmental medicine 05/2006; 63(4):237-43. · 3.64 Impact Factor
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ABSTRACT: The objective was to evaluate the prevalence of BRCA1/2 mutations in selected categories of ovarian cancer patients in Israel.
Blood samples and specimens of ovarian tumors were obtained in the course of a national case control study of women with ovarian cancer in Israel. Eight hundred ninety-six patients with epithelial ovarian cancer, 40 cases with nonepithelial ovarian cancer, and 68 with primary peritoneal cancer were tested for the BRCA mutations. Analysis of the three common BRCA mutations in Israel (185delAG, 5382insC in BRCA1, and 6174delT in BRCA2) was done using a multiplex polymerase chain reaction assay. A multivariate logistic regression model was used to assess the association of mutation carrier status and other factors (age, origin, family history, and clinical variables).
Of the 779 invasive epithelial ovarian cancer cases, 29.4% were mutation carriers. The prevalence of the mutations was higher among women below age 60 and in more advanced cases. The prevalence was low in mucinous tumors. There was almost a twofold excess of mutations among women with positive family history (45.7%), but still 26.5% of the family history negative cases were carriers. As expected, we found a higher rate of mutation carriers among the Ashkenazi group (34.2%) and 55% among Ashkenazi women with positive family history. No subjects born in North Africa were mutation positive.
BRCA mutations are strongly associated with ovarian cancer and they are present in variable rates in distinct age, ethnic, and histopathologic categories.
Gynecologic Oncology 07/2003; 89(3):494-8. · 3.89 Impact Factor
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ABSTRACT: During the years 1994-1999, a nationwide ovarian cancer case-control study was conducted in Israel. The present analysis addresses the question: Is epithelial ovarian cancer associated with body mass index at age 18 years and/or with weight changes in body mass index between adolescence and adult life? The study is based on 1,269 women with epithelial ovarian cancer and 2,111 matched controls. A significant decrease in risk of ovarian cancer was observed with parity, oral contraceptive use, and postmenopausal status. A significant increase in risk with family history of ovarian/breast cancer was also found. No significant association with age at menarche or infertility was found. For body mass index at age 18 years, the odds ratio of the highest versus lowest body mass index quartile was 1.42 (95% confidence interval: 1.08, 1.85) and after adjusting for confounders was 1.54 (95% confidence interval: 1.17, 2.02). However, no statistically significant risk associated with change in weight from age 18 years to adult life was found. The authors conclude that, in their population, body mass index at age 18 years is an independent risk factor for ovarian cancer.
American Journal of Epidemiology 02/2003; 157(2):113-20. · 5.22 Impact Factor
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ABSTRACT: The aim of the present study was to compare demographic and clinical characteristics of primary peritoneal carcinoma (PPC) to ovarian carcinoma (OvC) with regard to BRCA mutation frequencies.
Incident cases of histologically confirmed cancer of the ovary or peritoneum diagnosed in Israeli Jewish women between March 1, 1994, and June 30, 1999, were identified within the framework of an ongoing nationwide epidemiological study of these neoplasms in Israel. The present study comprises 609 (81.5% of 747) Jewish women with epithelial stage III-IV OvC and 68 (77.3% of 88) Jewish women with PPC who were genetically tested for the BRCA mutations. Data from each patient were collected by the aid of a prestructured questionnaire and medical records. Blood samples or tumor tissue was tested for the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutations in BRCA2.
A carrier rate of 28% of any BRCA 1/2 mutation was observed among the PPC group and of 30% among the invasive stage III-IV OvC. No differences were found between PPC and OvC neither in the overall distribution of BRCA1/2 mutation carrier rates nor according to type of mutation, age, ethnic origin, and histologic subtype. Among women with a positive family history, a higher rate of mutation carriers was observed in the PPC group compared to the OvC group (72.7 vs 43.8%, respectively, P = 0.07).
The similar frequency distribution of BRCA1/2 mutations in PPC and OvC observed in the present study indicates that these mutations may predispose to PPC as well and that this neoplasm is part of the hereditary breast-ovarian cancer syndrome.
Gynecologic Oncology 02/2003; 88(1):58-61. · 3.89 Impact Factor
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ABSTRACT: This study was undertaken in order to evaluate a possible genetic influence on the pathogenesis of ovarian dermoid cysts. We have performed a case-control study comparing the prevalence of a history of dermoid cysts in first-degree relatives of women with dermoid cysts and among first-degree relatives of women without dermoid cysts. The study group included 285 women with an established diagnosis of ovarian dermoid cysts. The control group included 378 women with sonographically normal ovaries. To assess the relationship between a first-degree family history of dermoid cysts and the diagnosis of ovarian dermoid cysts, a multivariate stepwise logistic regression model was applied. In 28 families of the study group (9.8%), a dermoid cyst was found in at least 1 first-degree relative as compared with only eight families (2%) among the controls (adjusted odds ratio -5.60; 95% CI 2.24-14.2). The data suggest a genetic predisposition towards dermoid cysts which merits further exploration.
Gynecologic and Obstetric Investigation 02/2003; 56(4):203-6. · 1.28 Impact Factor
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ABSTRACT: The objective of this paper is to assess whether ovarian hyperstimulation and in vitro fertilization (IVF) are associated with increased risk of cancer development, using an historical cohort analysis of infertile women who attended the IVF unit, Lis Maternity Hospital Tel Aviv Medical Center, Tel Aviv, Israel. One thousand and 82 women participated in the IVF treatment program between 1984 and 1992. Cancer incidence rates were determined through the National Cancer Registry and were compared to the expected rates with respect to appropriate age and continent of birth. Twenty-one cases of cancer were observed as compared to 11 that were expected (SIR 1.91; 95% CI 1.18–2.91). When cancer cases that were diagnosed within one year of the IVF treatment were excluded from the analysis (SIR = 1.46; 95% CI 0.83–2.36), no significant excess risk of cancer was noted. We conclude that in this cohort of infertile women, the higher than expected cancer rate could not be attributed to IVF treatments. Special attention should be made to women who may be diagnosed with cancer during or shortly after IVF treatment.
International Journal of Gynecological Cancer 12/2002; 13(1):23 - 27. · 1.65 Impact Factor
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ABSTRACT: Using a theoretical framework that divided social factors measures into structure, function, and social engagement, this study determined those aspects of social networks most significantly associated with 8-year, all-cause mortality among the old-old in Israel.
Jews (n = 1,340) aged 75-94 living in Israel on January 1, 1989, were randomly selected from the National Population Register; stratified by age, sex, and place of birth; and interviewed in person. Mortality was determined according to the National Death Registry (December 1997).
After controlling for sociodemographics and measures of health, cognitive status, depressive symptoms, and physical function, the measures of social engagement that explicitly involved others were associated with a lower risk of mortality. No measure of the function of the social network was associated with risk of mortality. Living in the community without a spouse and with a child and living in an institution were significantly associated with a higher risk of mortality.
The finding that participating in activities with people outside of the immediate family is associated with a lower risk of death has practical implications for helping the aging population and their families in their decision-making process. Lack of support for the hypothesis that those with more social support would show reduced risk of mortality may indicate that the positive effect of perceiving support and the negative effect of needing support may cancel each other out and result in no perceived effect. In this population, the association between socioeconomic status (SES) and the risk of mortality seems to be expressed through the living arrangements, with the sick and frail, both in institutions (higher SES) and in the community with a child or other (lower SES), having a higher risk of mortality. These findings are consistent with the use of children as a substitute for institutionalization, and imply that at least some cohabitation was the caretaking solution for the noninstitutionalized old-old who were of low SES, frail, and close to death.
The Journals of Gerontology Series B Psychological Sciences and Social Sciences 10/2002; 57(5):S308-18. · 2.62 Impact Factor
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Y Ben David, A Chetrit,
G Hirsh-Yechezkel,
E Friedman,
B D Beck,
U Beller,
G Ben-Baruch,
A Fishman,
H Levavi,
F Lubin,
J Menczer,
B Piura,
J P Struewing,
B Modan
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ABSTRACT: To study the role of BRCA mutations in ovarian cancer survival.
Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors.
This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease.
Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.
Journal of Clinical Oncology 02/2002; 20(2):463-6. · 18.37 Impact Factor
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ABSTRACT: To date, there is no data regarding the association of patient in-hospital referral source and stroke rehabilitation outcomes. The objective of the present study was to investigate the possible relation between in-hospital referring source, whether directly from an emergency ward (EW) or indirectly through a general medical ward (GMW), and the functional outcomes achieved during rehabilitation of such stroke patients. This retrospective observational study included 315 consecutive patients, admitted for rehabilitation following the onset of acute stroke. We compared those referred directly to us from the EW, with others referred from GMWs. Functional status was assessed by Functional Independence Measure method (FIM). Functional outcome was determined by total FIM gain (efficacy) and daily FIM gain (efficiency), both absolute and relative (to potential). The two study groups were similar in terms of age, gender, and diagnosis. FIM admission scores were higher at admission in patients admitted directly from the EW, compared with those referred from GMWs (72.5 +/- 27.5 and 62.7 +/- 25.6, respectively) but similar at discharge (77.4 +/- 28.8 and 80.7 +/- 32.5, respectively). Length of stay (LOS) in the GMW group was longer as compared to the EW group. Efficacy was significantly associated with being married, younger age, hemiplegia, and admission scores between 40-60. Both absolute and relative efficacy and efficiency rates of rehabilitation were significantly lower among patients referred from the EW. We conclude that in-hospital referral source is associated with different rehabilitation outcomes in stroke patients. Direct admission of stroke patients from the EW is associated with lower rehabilitation efficacy and efficiency rates, compared with those admitted from GMWs. The findings support the implementation of different selection methods, underscoring the need of both clinicians and administrators to consider the in-hospital referral source as a potential factor associated with stroke rehabilitation outcome.
Aging (Milan, Italy) 01/2002; 13(6):430-6.
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J Y Streifler,
N Rosenberg, A Chetrit,
R Eskaraev,
B A Sela,
R Dardik,
A Zivelin,
B Ravid,
J Davidson,
U Seligsohn,
A Inbal
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ABSTRACT: Although risk factors for carotid artery stenosis caused by atherosclerosis are known, it is unclear what triggers "activation" of the atherosclerotic plaques and the ensuing thromboembolic cerebral events. The aim of this study was to evaluate whether thrombophilic factors, platelet glycoprotein (GP) polymorphisms, and homocysteine are associated with a risk of ischemic events in patients with significant carotid stenosis.
Consecutive patients with >/=50% carotid stenosis, whether symptomatic (with ipsilateral ischemic events) or asymptomatic, who were evaluated and followed in a neurovascular clinic were tested for plasma levels of homocysteine, C677T mutation in methylenetetrahydrofolate reductase, G20210A mutation of factor II, factor V Leiden, antiphospholipid antibodies, and polymorphisms of platelet membrane GP: human platelet antigen (HPA)-1, GP Ia (C807T), and GP Ib (variable number of tandem repeats, Kozak, and HPA-2).
Eighty-six asymptomatic and 67 symptomatic patients were evaluated. The former group was older (73.7+/-6.9 versus 69.5+/-9.1 years, P=0.02). Major risk factors for stroke were similar in both groups. In symptomatic patients versus asymptomatic patients, hyperhomocysteinemia was 3-fold more frequent (34.3% versus 12.8%, respectively; P=0.002) and HPA-1a/b was almost 2-fold more common (38.8% versus 20.9%, respectively; P=0.01). All other thrombophilic factors and platelet polymorphisms studied did not differ significantly between the 2 groups. Multivariate analysis revealed that hyperhomocysteinemia and the HPA-1a/b genotype conferred a significant risk of cerebral ischemic events, with odds ratios (95% CI) of 4.07 (1.7 to 9.7) and 3.4 (1.5 to 7.8), respectively.
Hyperhomocysteinemia and HPA-1a/b are independent risk factors for ischemic events in patients with significant carotid stenosis.
Stroke 12/2001; 32(12):2753-8. · 5.73 Impact Factor
