CHADS2 and CHA2DS2-VASc are validated scores used to predict stroke in patients with atrial fibrillation. Many of the individual risk factors included in these scores are also risk factors for atrial ...fibrillation. We aimed to examine the performance of CHADS2 and CHA2DS2-VASc scores in predicting new-onset atrial fibrillation in subjects without preexisting diagnosis of atrial fibrillation.
Using the computerized database of the largest health maintenance organization in Israel, we identified all adults aged 50 years or older without atrial fibrillation prior to January 1, 2012. CHADS2 and CHA2DS2-VASc scores were calculated for each participant at study entry, and the cohort was followed for incident atrial fibrillation until December 31, 2014.
Of 1,062,073 subjects without preexisting diagnosis of atrial fibrillation; 23,223 developed atrial fibrillation during a follow-up of 3,053,754 person-years (incidence rate, 0.76 per 100 person-years). Incidence rate of atrial fibrillation increased in a graded manner with increasing CHA2DS2-VASc score: 0.17, 0.21, 0.49, 0.94, 1.65, 2.31, 2.75, 3.39, 4.09, and 6.71 per 100 person-years for CHA2DS2-VASc score of 0 to 9 points, respectively (P < .001). The hazard ratio for atrial fibrillation for each 1-point increase in CHA2DS2-VASc score was 1.57 (95% confidence interval CI, 1.56-1.58). Results were similar for CHADS2 score. The area under the receiver operating characteristic curve to predict new-onset atrial fibrillation was 0.728 (95% CI, 0.725-0.711) and 0.744 (95% CI, 0.741-0.747) for CHADS2 and CHA2DS2-VASc scores, respectively.
CHADS2 and CHA2DS2-VASc scores are directly associated with the incidence of new-onset atrial fibrillation, and have a relatively high performance for atrial fibrillation prediction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
While clinical outcomes from colorectal cancer (CRC) are influenced by stage at diagnosis and treatment, mounting evidence suggests that an enhanced lymphocytic reaction to a tumor may also be an ...informative prognostic indicator.
The roles of intratumoral T lymphocyte infiltration (TIL), peritumoral Crohn's-like lymphoid reaction (CLR), microsatellite instability (MSI), and clinicopathological characteristics in survival from CRC were examined using 2369 incident CRCs from a population-based case-control study in northern Israel. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in multivariable models adjusted for age, sex, ethnicity, grade, stage, and MSI. All statistical tests were two-sided.
Tumors with TIL/high-powered field (HPF) of 2 or greater were associated with a statistically significant increase in CRC-specific (P < .001) and overall survival (P < .001) compared with tumors with TIL/HPF of less than 2. Similarly, tumors with a prominent CLR experienced better CRC-specific (P < .001) and overall survival (P < .001) as compared with those with no response. High TILs (HR = 0.76, 95% CI = 0.64 to 0.89, P < .001) and a prominent CLR (HR = 0.71, 95% CI = 0.62 to 0.80, P < .001), but not MSI, were associated with a statistically significant reduction in all-cause mortality after adjustment for established prognostic factors.
TILs and CLR are both prognostic indicators for CRC after adjusting for traditional prognostic indicators.
Bisphosphonates are commonly used for the treatment of osteoporosis and for prevention and treatment of skeletal lesions due to malignancy. However, the association between the use of bisphosphonates ...and the risk of developing breast cancer has not been reported.
The Breast Cancer in Northern Israel Study is a population-based case-control study in northern Israel of patients with breast cancer and age-, clinic-, and ethnic-group matched controls. Use of bisphosphonates was assessed in 4,039 postmenopausal patients and controls, members of Clalit Health Services, using pharmacy records.
The use of bisphosphonates for longer than 1 year before diagnosis, but not for shorter than 1 year, was associated with a significantly reduced relative risk of breast cancer (odds ratio OR, 0.61; 95% CI, 0.50 to 0.76). This association remained significant after adjustment for age, fruit, and vegetable consumption, sports activity, family history of breast cancer, ethnic group, body mass index, use of calcium supplements, hormone replacement therapy use, number of pregnancies, months of breast feeding, and age at first pregnancy (OR, 0.72; 95% CI, 0.57 to 0.90). Breast cancer risk did not change further if bisphosphonates were used for more years. Breast tumors identified in bisphosphonates users were more often estrogen receptor positive and less often poorly differentiated.
The use of bisphosphonates for longer than 1 year was associated with a 28% relative reduction in the risk of postmenopausal breast cancer. Tumors developing under bisphosphonates treatment tended to have a favorable prognostic factors profile.
Abstract Objective Low 25(OH)D levels are associated with increased parathyroid hormone levels leading to progressive bone loss. The serum levels of 25(OH)D sufficient to keep the parathyroid hormone ...level at a range that will prevent bone loss are still unclear. The current study was aimed at evaluating the relationship between 25(OH)D levels and concomitant parathyroid hormone levels. Methods The computerized laboratory database of Clalit Health Services, a not-for-profit health maintenance organization covering more than half of the Israeli population, was searched for all 25(OH)D and parathyroid hormone tests performed in 2009. Concomitant tests of parathyroid hormone and 25(OH)D were identified in 19,172 people. Results Serum parathyroid hormone levels were inversely correlated with 25(OH)D levels ( r = −0.176, P < .001); 25(OH)D levels less than 50 nmol/L were associated with a steep increase in parathyroid hormone levels and hyperparathyroidism, which decreased with increasing 25(OH)D levels and reached a plateau at 25(OH)D levels of 75 to 85 nmol/L. The quadratic fit with plateau model showed that parathyroid hormone stabilizes at 25(OH)D level of 78.9 nmol/L. However, after excluding 5449 people with hypercalcemia or renal failure, the parathyroid hormone plateau was attained at a significantly lower 25(OH)D cut point of 46.2 nmol/L. Conclusion Our data suggest that a 25(OH)D threshold of 50 nmol/L is sufficient for parathyroid hormone suppression and prevention of secondary hyperparathyroidism in persons with normal renal function. 25(OH)D levels greater than 75 nmol/L do not seem to be associated with additional change in parathyroid hormone levels.
Abstract Purpose The use of statins has been associated with reduced risk of malignancies in a variety of organ sites. This study was aimed at studying the effects of statins on gynecological ...cancers. Methods The Cancer in The Ovary and Uterus Study (CITOUS) is a case–control study of newly diagnosed cases of gynecological malignancies and age/sex/clinic/ethnic-group matched population controls. Use of statins prior to and following diagnosis was assessed in a subset of 424 cases of ovarian and endometrial cancers and 341 controls, enrolled in Clalit Health Services (CHS), using pharmacy records. Results The use of statins for more than one year prior to diagnosis was associated with a significantly reduced risk of ovarian cancer (OR = 0.56, 95% CI: 0.33–0.94) and of endometrial cancer (OR = 0.59, 95% CI: 0.40–0.87). The association with endometrial cancer, but not with ovarian cancer (OR = 0.54, 0.26–1.13), remained statistically significant after adjustment for fruit and vegetable consumption, sports activity, family history of endometrial and colorectal cancer, ethnicity, BMI, duration of breast feeding, age at 1st pregnancy and use of menopausal hormones (RR = 0.48, 0.26–0.89). Women who used statins only after diagnosis of cancer had a significantly better survival of both ovarian cancer (Log rank test, p = 0.021, age adjusted HR = 0.47, 0.26–0.85) and endometrial cancer ( p = 0.06, age adjusted HR = 0.45, 0.23–0.87). Conclusion The use of statins for more than one year before diagnosis was associated with a reduction in the risk of endometrial cancer and possibly ovarian cancer. A significantly improved survival of cases of both malignancies was noticed when statins were taken only after diagnosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast ...cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.
A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.
In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96,
= 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91,
= 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.
The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival.
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An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this ...association remain unclear.
Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF.
AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases.
Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To identify risk factors for the development of statin-associated diabetes mellitus (DM).
The study was conducted in two phases. Phase one involved high-throughput in silico processing of a large ...amount of biomedical data to identify risk factors for the development of statin-associated DM. In phase two, the most prominent risk factor identified was confirmed in an observational cohort study at Clalit, the largest health care organization in Israel. Time-dependent Poisson regression multivariable models were performed to assess rate ratios (RRs) with 95% CIs for DM occurrence.
A total of 39,263 statin nonusers were matched by propensity score to 20,334 highly compliant statin initiators in 2004-2005 and followed until the end of 2010. Within 59,597 statin users and nonusers in a multivariable model, hypothyroidism and subclinical hypothyroidism carried an increased risk for DM (RR 1.53 95% CI 1.31-1.79 and 1.75 1.40-2.18, respectively). Hypothyroidism increased DM risk irrespective of statin treatment (RR 2.06 1.42-2.99 and 1.66 1.05-2.64 in statin users and nonusers, respectively). Subclinical hypothyroidism risk for DM was prominent only upon statin use (RR 1.94 1.13-3.34 and 1.20 0.52-2.75 in statin users and nonusers, respectively). Patients with hypothyroidism treated with thyroid hormone replacement therapy were not at increased risk for DM.
Hypothyroidism is a risk factor for DM. Subclinical hypothyroidism-associated risk for DM is prominent only upon statin use. Identifying and treating hypothyroidism and subclinical hypothyroidism might reduce DM risk. Future clinical studies are needed to confirm the findings.
Bisphosphonates are commonly used for the treatment of osteoporosis and bone metastases caused by breast cancer and were recently reported to be associated with a reduced risk of breast cancer, ...possibly acting through the mevalonate pathway, but their association with risk of other cancers is unknown.
The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study in northern Israel of patients with colorectal cancer and age-, sex-, clinic-, and ethnic group-matched controls. Long-term use of bisphosphonates before diagnosis was assessed in a subset of 933 pairs of postmenopausal female patients and controls, enrolled in Clalit Health Services, using computerized pharmacy records.
The use of bisphosphonates for more than 1 year before diagnosis, but not for less than 1 year, was associated with a significantly reduced relative risk (RR) of colorectal cancer (RR, 0.50; 95% CI, 0.35 to 0.71). This association remained statistically significant after adjustment in a model for vegetable consumption, sports activity, family history of colorectal cancer, body mass index, and use of low-dose aspirin, statins, vitamin D, and postmenopausal hormones (RR, 0.41; 95% CI, 0.25 to 0.67). Concomitant use of bisphosphonates and statins did not further reduce the risk.
The use of oral bisphosphonates for more than 1 year was associated with a 59% relative reduction in the risk of colorectal cancer, similar to the recently reported association of this drug class with reduction in breast cancer risk.
Context and Objectives:
Vitamin D plays a key role in maintaining bone health, but evidence for its nonskeletal effects is inconsistent. This study aims to examine the association between serum ...25-hydroxyvitamin D 25(OH)D levels and all-cause mortality in a large general population cohort.
Design, Participants, and Setting:
Using the computerized database of the largest health care provider in Israel, we identified a cohort of subjects 20 years old or older with serum 25(OH)D levels measured between January 2008 and December 2009. Vital status was ascertained through August 2011.
Results:
Median follow-up was 28.5 months (interquartile range 23.8–33.5 months); 7,247 of 182,152 participants (4.0%) died. Subjects who died had significantly lower serum 25(OH)D levels (mean 44.8 ± 24.2 nmol/liter) than those alive at the end of follow-up (51.0 ± 23.2 nmol/liter), P < 0.001. After adjustment for age, gender, ethnicity, and seasonality, the hazard ratio (HR) for all-cause mortality was 2.02 95% confidence interval (CI) 1.89–2.15 for the lowest serum 25(OH)D quartile (<33.8 nmol/liter) compared with the highest. After further adjustment for comorbidity, use of vitamin D supplements and statins, smoking, socioeconomic status, and body mass index, the HR was 1.81 (95% CI 1.69–1.95). This remained, even after adjustment for serum low-density lipoprotein, high-density lipoprotein, calcium level (corrected for serum albumin levels), and glomerular filtration rate, 1.85 (95% CI 1.70–2.01). The fully adjusted HR associated with being in the second 25(OH)D quartile (33.8–49.4 nmol/liter) was 1.25 (95% CI 1.16–1.34).
Conclusions:
All-cause mortality is independently and inversely associated with serum 25(OH)D levels at levels less than 50 nmol/liter.
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