Roberta M. Ray

Factors influencing survival after out-of-hospital cardiac arrest.

Survival to hospital discharge was related to the clinical history and emergency care system factors in 285 patients with witnessed cardiac arrest due to ventricular fibrillation. Only the emergency care factors were associated with differences in outcome. Both the period from collapse until initiation of basic life support and the duration of basic life support before delivery of the first defibrillatory shock were shorter in patients who survived compared with those who died (3.6 +/- 2.5 versus 6.1 +/- 3.3 minutes and 4.3 +/- 3.3 versus 7.3 +/- 4.2 minutes; p less than 0.05). A linear regression model based on emergency response times for 942 patients discovered in ventricular fibrillation was used to estimate expected survival rates if the first-responding rescuers, in addition to paramedics, had been equipped and trained to defibrillate. Expected survival rates were higher with early defibrillation (38 +/- 3%; 95% confidence limits) than the observed rate (28 +/- 3%). Because outcome from cardiac arrest is primarily influenced by delays in providing cardiopulmonary resuscitation and defibrillation, factors affecting response time should be carefully examined by all emergency care systems.

Considerations for improving survival from out-of-hospital cardiac arrest

Since the implementation of a paramedic system in Seattle, yearly survival rates from out-of-hospital cardiac arrest due to ventricular fibrillation have averaged 25% without any significant increase over the years. Outcome for cardiac arrest associated with other rhythms has been poor: when asystole was the first rhythm recorded, only 1% of patients survived; when electromechanical dissociation was initially present, only 6% survived. For cases of electromechanical dissociation, neither the type of rhythm nor the rate appear to influence outcome. Survival from ventricular fibrillation can be improved by shortening the delay to initiation of CPR and to defibrillation. When outcome in 244 witnessed arrests was related to the times to beginning CPR and to initial defibrillation, mortality increased 3% each minute until CPR was begun and 4% a minute until the first shock was delivered. New strategies that minimize delays appear to have the greatest promise for improving survival after cardiac arrest.

Duration of Lactation and Risk Factors for Maternal Cardiovascular Disease

OBJECTIVE: To examine dose–response relationships between the cumulative number of months women lactated and postmenopausal risk factors for cardiovascular disease. METHODS: We examined data from 139,681 postmenopausal women (median age 63 years) who reported at least one live birth on enrolling in the Women’s Health Initiative observational study or controlled trials. Multivariable models were used to control for sociodemographic (age, parity, race, education, income, age at menopause), lifestyle, and family history variables when examining the effect of duration of lactation on risk factors for cardiovascular disease, including obesity (body mass index [BMI] at or above 30), hypertension, self-reported diabetes, hyperlipidemia, and prevalent and incident cardiovascular disease. RESULTS: Dose-response relationships were seen; in fully adjusted models, women who reported a lifetime history of more than 12 months of lactation were less likely to have hypertension (odds ratio [OR] 0.88, P<.001), diabetes (OR 0.80, P<.001), hyperlipidemia (OR 0.81, P<.001), or cardiovascular disease (OR 0.91, P=.008) than women who never breast-fed, but they were not less likely to be obese. In models adjusted for all above variables and BMI, similar relationships were seen. Using multivariate adjusted prevalence ratios from generalized linear models, we estimate that among parous women who did not breast-feed compared with those who breast-fed for more than 12 months, 42.1% versus 38.6% would have hypertension, 5.3% versus 4.3% would have diabetes, 14.8% versus 12.3% would have hyperlipidemia, and 9.9% versus 9.1% would have developed cardiovascular disease when postmenopausal. Over an average of 7.9 years of postmenopausal participation in the Women’s Health Initiative, women with a single live birth who breast-fed for 7–12 months were significantly less likely to develop cardiovascular disease (hazard ratio 0.72, 95% confidence interval 0.53–0.97) than women who never breast-fed. CONCLUSION: Among postmenopausal women, increased duration of lactation was associated with a lower prevalence of hypertension, diabetes, hyperlipidemia, and cardiovascular disease. LEVEL OF EVIDENCE: II

Effect of Calcium and Vitamin D Supplementation on Blood Pressure. The Women's Health Initiative Randomized Trial

Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Womens Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: −0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: −0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.

Improved neurologic recovery and survival after early defibrillation.

Eighty-seven patients who had out-of-hospital cardiac arrests received defibrillating shocks delivered by minimally trained first responders before the arrival of paramedics in a city with short emergency response times. Their outcomes were compared with those of 370 other victims who received only basic life support by first responders until paramedics arrived. Survival was improved by early defibrillation in cases in which there was a delay in initiating cardiopulmonary resuscitation and in which paramedic response times exceeded 9 min; there was 62% survival after early defibrillation by first responders and 27% if first responders provided only basic life support (p less than .02). Neurologic recovery was also improved after early defibrillation. Eighteen of 46 resuscitated patients (39%) receiving early defibrillation were awake at 24 hr compared with 49 of 204 patients (24%) who received only basic life support while awaiting paramedics (p less than .02). Incorporating defibrillation as part of basic life support can reduce both mortality and morbidity from cardiac arrest, even in cities with established, rapidly responding emergency care systems.

Smoking as a Risk Factor for Recurrence of Sudden Cardiac Arrest

We obtained information about cessation of smoking in 310 survivors of out-of-hospital cardiac arrest who had been habitual cigarette smokers at the time of their arrest. Patients with coronary heart disease were stratified according to mortality risk on the basis of recognized criteria. The expected first-year rate of recurrent arrest ranged from 2 to 40 percent among the strata. Life-table analyses showed that reformed smokers had a lower incidence of recurrent arrest than patients who continued to smoke (19 vs. 27 percent at three years; P = 0.038 by one-sided test adjusted across strata). This effect occurred to varying degrees in all but the highest risk stratum. No differences in survival were observed for mortality due to other causes. It is possible that continued smoking in these patients led to acceleration of an ongoing atherosclerotic process, but the differences in early survival suggest that smoking may also act in the short term to enhance vulnerability to cardiac arrest.

Cervical carcinoma and reproductive factors: Collaborative reanalysis of individual data on 16,563 women with cervical carcinoma and 33,542 women without cervical carcinoma from 25 epidemiological studies.

The International Collaboration of Epidemiological Studies of Cervical Cancer has combined individual data on 11,161 women with invasive carcinoma, 5,402 women with cervical intraepithelial neoplasia (CIN)3/carcinoma in situ and 33,542 women without cervical carcinoma from 25 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of cervical carcinoma in relation to number of full‐term pregnancies, and age at first full‐term pregnancy, were calculated conditioning by study, age, lifetime number of sexual partners and age at first sexual intercourse. Number of full‐term pregnancies was associated with a risk of invasive cervical carcinoma. After controlling for age at first full‐term pregnancy, the RR for invasive cervical carcinoma among parous women was 1.76 (95% CI: 1.53–2.02) for ≥≥7 full‐term pregnancies compared with 1–2. For CIN3/carcinoma in situ, no significant trend was found with increasing number of births after controlling for age at first full‐term pregnancy among parous women. Early age at first full‐term pregnancy was also associated with risk of both invasive cervical carcinoma and CIN3/carcinoma in situ. After controlling for number of full‐term pregnancies, the RR for first full‐term pregnancy at age <17 years compared with ≥≥25 years was 1.77 (95% CI: 1.42–2.23) for invasive cervical carcinoma, and 1.78 (95% CI: 1.26–2.51) for CIN3/carcinoma in situ. Results were similar in analyses restricted to high‐risk human papilloma virus (HPV)‐positive cases and controls. No relationship was found between cervical HPV positivity and number of full‐term pregnancies, or age at first full‐term pregnancy among controls. Differences in reproductive habits may have contributed to differences in cervical cancer incidence between developed and developing countries.

BRCA1 and BRCA2 mutations in women from Shanghai China

Little is known about the frequency of germ-line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the distribution of BRCA1 and BRCA2 germ-line mutations and polymorphisms in a cohort of women from Shanghai, China. Study subjects totaled 1306, and included 645 women with breast cancer, 342 women with benign breast disease, and 319 unaffected controls, born between 1924 and 1958, selected from women enrolled in a randomized trial of Breast Self-Examination in Shanghai, China. Women were selected without regard to family history of breast or ovarian cancer. All of the coding regions and exon-intron boundaries were screened. Data were analyzed with respect to age at diagnosis, and family history of breast and ovarian cancer. The prevalence of known disease-associated mutations in women with breast cancer was 1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease-associated mutations, respectively. Overall, these results suggest that inherited susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women with a family history of breast cancer is comparable between women from Shanghai and Caucasian women of Western European descent. Most alterations observed appear unique to the Chinese population, suggesting a resource that will be useful for assessing risk among both Chinese women and United States women of Chinese descent.

Dietary risk factors for invasive and in-situ cervical carcinomas in Bangkok, Thailand

OBJECTIVE: Although human papillomavirus (HPV) may be a necessary cause of cervical cancer, most women with HPV infections do not develop this disease. This study was conducted to evaluate the possible effects of specific dietary factors on cervical carcinogenesis.METHODS: Fifty hospitalized in-situ cases and 125 controls were identified from family planning or gynecologic clinics associated with Siriraj hospital in Bangkok, Thailand, and 134 hospitalized invasive cases and 384 hospitalized controls from the public wards of Siriraj Hospital were administered a food-frequency questionnaire and tested for HPV DNA in exfoliated cervical cells. Odds ratios in relation to intake of foods high in vitamin C, folate, vitamin E, vitamin A, β-carotene, retinol, and cruciferous vegetables were estimated using logistic regression in case–control comparisons and in case–case comparisons adjusted for HPV status.RESULTS: High intake of foods rich in vitamin A, and particularly high-retinol foods, were associated with a reduced risk of in-situ disease and less strongly also with a reduced risk of invasive as compared to in-situ disease. No association was found between intake of cruciferous vegetables, foods high in vitamin C, folate, vitamin E, and β-carotene and risk of either in-situ or invasive cervical cancer.CONCLUSIONS: Increasing intake of foods rich in total vitamin A, and particularly high-retinol foods, may reduce risk of in-situ cervical cancer, and at the highest level of intake may inhibit progression to invasion. If others confirm these results they suggest means of reducing the risk of cervical cancer that are amenable to public health action.

Use of Medicare Data to Identify Coronary Heart Disease Outcomes in the Women’s Health Initiative

Background—Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials or clinical registry studies. The reliability of claims data for documenting outcomes is unknown. Methods and Results—We linked records of Women’s Health Initiative (WHI) participants aged ≥65 years to Medicare claims data and compared hospitalizations that had diagnosis codes for acute myocardial infarction or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI-adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI-adjudicated outcomes and Medicare claims was good for the diagnosis of myocardial infarction (&kgr;, 0.71–0.74) and excellent for coronary revascularization (&kgr;, 0.88–0.91). The hormone:placebo hazard ratio for clinical myocardial infarction was 1.31 (95% confidence interval, 1.03–1.67) based on WHI outcomes and 1.29 (95% confidence interval, 1.00–1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (95% confidence interval, 0.88–1.35) based on WHI outcomes and 1.10 (95% confidence interval, 0.89–1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1000 bootstrap replications. Conclusions—Medicare claims may provide useful data on coronary heart disease outcomes among patients aged ≥65 years in clinical research studies. Clinical Trials Registration Information—URL: www.clinicaltrials.gov. Unique identifier: NCT00000611.