Mikel Aickin

Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet

Background The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. Methods A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. Results Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during t...

Electronic medical record reminder improves osteoporosis management after a fracture: a randomized, controlled trial.

OBJECTIVES: Osteoporosis treatment rates after a fracture are low. This study evaluated methods to increase guideline‐recommended osteoporosis care postfracture.

Lack of impact of therapy on extent of Barrett's esophagus in 67 patients

Sixty-seven patients with Barretts esophagus have been prospectively followed over an average of 36 months (range 6 to 76 months) with standardized endoscopic observation and biopsies of the length of columnar epithelium. The initial length of Barretts epithelium ranged from 1 to 16 cm, mean 5.5 cm. Specialized columnar epithelium was present in 64 of the 67 patients. Patients were treated predominantly with H2-receptor blocker therapy to relieve symptoms. Eighty-two percent of patients had less than a 1-cm change in length per year. The mean rate of change of length was −0.093 cm per year. These results confirm in a relatively large, prospective study that standard antireflux therapy for Barretts esophagus does not result in consistent reduction in the extent of Barretts epithelium over a three-year interval.

Fat or lean tissue mass: which one is the major determinant of bone mineral mass in healthy postmenopausal women?

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1‐year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1‐year follow‐up. Dual‐energy X‐ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross‐sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.

Screening for bacterial vaginosis in pregnancy.

CONTEXT Bacterial vaginosis (BV) is a strong independent risk factor for adverse pregnancy outcomes. BV is found in 9% to 23% of pregnant women. Symptoms include vaginal discharge, pruritus, or malodor, but often women with BV are asymptomatic. OBJECTIVES To determine whether screening and treating pregnant women for BV reduces adverse pregnancy outcomes, as part of an assessment for the U.S. Preventive Services Task Force. DATA SOURCES Randomized clinical trials of BV treatment in pregnancy that measured pregnancy outcomes were identified from multiple searches in MEDLINE from 1966 to 1999, the Cochrane Controlled Trials Register and Library, and national experts. STUDY SELECTION All randomized controlled trials of BV treatment in pregnancy that specifically measured pregnancy outcomes. DATA EXTRACTION The following information was abstracted: study design and blinding, diagnostic methods, antibiotic interventions, timing of antibiotic treatment in pregnancy, criteria for treatment, comorbidities, demographic details, risk factors for preterm delivery such as previous preterm delivery, compliance, rates of spontaneous and total preterm delivery less than 37 weeks and less than 34 weeks, preterm premature rupture of membranes, low birth weight less than 2500 grams, spontaneous abortion, postpartum endometritis, and neonatal sepsis. For each study, we measured the effect of treatment by calculating the difference in the rate of a given pregnancy outcome in the control group minus the treatment group (the absolute risk reduction [ARR]). A stepwise procedure based on the profile likelihood was applied to assess heterogeneity, to pool studies when appropriate, and to calculate the mean and 90% confidence intervals (CIs) for the effect of treatment. DATA SYNTHESIS Seven randomized controlled trials met inclusion criteria for the meta-analysis. We found no benefit to BV treatment in average-risk women for any pregnancy outcome. Results of studies of high-risk populations, women with previous preterm delivery, were statistically heterogeneous. They clustered into two groups; one showed no benefit (ARR=-0.08, 90% CI=-0.19 to 0.04), whereas the three homogeneous studies showed potential benefit of BV treatment (pooled ARR=0.22; 90% CI=0.13 to 0.31) for preterm delivery before 37 weeks. Four high-risk studies reported results for preterm delivery less than 34 weeks. The pooled estimate showed no benefit (ARR=0.04; 90% CI=-0.02 to 0.09), but variation was noted among individual studies. Two trials of high-risk women found an increase in preterm delivery less than 34 weeks in women who did not have BV but received BV treatment. Comparisons of patient populations, treatment regimens, and study designs did not explain the heterogeneity among studies. CONCLUSIONS We found no benefit to routine BV screening and treatment. A subgroup of high-risk women may benefit from BV screening and treatment; however, there may be a subgroup for whom BV treatment could increase the occurrence of preterm delivery.

Older Women with Fractures: Patients Falling Through the Cracks of Guideline-Recommended Osteoporosis Screening and Treatment

BACKGROUND Many older patients with fractures are not managed in accordance with evidence-based clinical guidelines for osteoporosis. Guidelines recommend that these patients receive treatment for clinically apparent osteoporosis or have bone mineral density measurements followed by treatment when appropriate. This cohort study was conducted to further characterize the gap between guidelines and actual practice with regard to bone mineral density measurement and treatment of older women after a fracture. Our purpose was to aid in the design of more effective future interventions. METHODS We identified female members of a not-for-profit group-model health maintenance organization who were fifty years of age or older and who had a diagnosis of a new fracture as defined in the study. We used administrative databases and the clinical electronic medical records to obtain data on demographics, diagnoses, drugs dispensed by the pharmacy, and the measurement of bone mineral density. RESULTS The study population included 3812 women with an average age of 71.3 years. Fewer than 12% of the women had a diagnosis of osteoporosis prior to the index fracture; 10.7% had an increased risk for secondary osteoporosis and 38.8%, for falls because of a diagnosis or medication. It was found that 46.4% of the study population had been managed as specified by clinical guidelines. The patients who had been managed as specified by the guidelines were younger and less likely to have the risk factor of a weight of <127 lb (58 kg), a hip fracture, or a wrist fracture. They were also more likely to be taking steroids on a chronic basis and to have had a vertebral fracture. The percentage of women who had measurement of bone mineral density increased during the study period, from 1.3% in 1998 to 10.2% in 2001. Of the patients receiving treatment for osteoporosis, 73.6% adhered to the treatment regimen. CONCLUSIONS Adherence to guidelines for evaluation and treatment for osteoporosis after a patient sustained a fracture did not improve between 1998 and 2001 despite the promulgation of evidence-based guidelines. Methods to enhance education and facilitate processes of care will be necessary to reduce this gap. It may be fruitful to target high-risk subgroups for tailored interventions for prevention of refracture.

Premier: a clinical trial of comprehensive lifestyle modification for blood pressure control: rationale, design and baseline characteristics

PURPOSE To describe PREMIER, a randomized trial to determine the effects of multi-component lifestyle interventions on blood pressure (BP). METHODS Participants with above optimal BP through stage 1 hypertension were randomized to: 1) a behavioral lifestyle (BLS) intervention that implements established recommendations, 2) a BLS intervention that implements established recommendations plus the DASH diet, or 3) an advice only standard of care group. The two BLS interventions consist of group and individual counseling sessions for 18 months. The primary outcome is systolic BP at 6 months. Additional outcomes include diastolic BP and homocysteine at 6 months; systolic and diastolic BP at 18 months; fasting lipids, glucose and insulin at 6 and 18 months; and effects in subgroup. CONCLUSION Results from the PREMIER trial will provide scientific rationale for implementing multi-component behavioral lifestyle intervention programs to control BP and prevent CVD.

Efficacy of cervical endplay assessment as an indicator for spinal manipulation.

Study Design. Double-blind, randomized, placebo-controlled trial. Objectives. To evaluate the effect of manual endplay assessment on neck pain and stiffness outcomes in neck pain patients receiving spinal manipulation. Summary of the Background Data. There have been no studies on the efficacy of palpation used as an indicator for manipulation in the management of back and neck pain. Methods. Neck pain patients (n = 104) were randomly assigned to two groups. The study group received manipulation targeted to individual cervical vertebrae according to endplay restriction noted by the examining clinician. The control group received manipulation determined by sham, computer-generated examination findings; endplay examination was ignored and served as a placebo assessment. Treatment was rendered on a single occasion by a chiropractor. Outcomes were neck pain and stiffness assessed before and after manipulation and at least 5 hours following treatment. Results. The study and control groups showed clinically important improvement in neck pain and stiffness. However, there were no clinically important or statistically significant differences between the study and control groups in terms of pain or stiffness outcomes. Findings were robust across patient, complaint, and treatment characteristics. Conclusions. Endplay assessment in and of itself did not contribute to the same-day pain and stiffness relief observed in neck pain patients receiving spinal manipulation. The impact on a longer course of treatment remains to be investigated. The data suggest that pain modulation may not be limited to mechanisms associated with manipulation of putative motion restrictions.

The DASH Diet, Sodium Intake and Blood Pressure Trial (DASH-Sodium): Rationale and Design

The DASH Diet, Sodium Intake and Blood Pressure Trial (DASH-Sodium) is a multicenter, randomized trial comparing the effects of 3 levels of sodium intake and 2 dietary patterns on blood pressure among adults with higher than optimal blood pressure or with stage 1 hypertension (120-159/80-95 mm Hg). The 2 dietary patterns are a control diet typical of what many Americans eat, and the DASH diet, which, by comparison, emphasizes fruits, vegetables, and low-fat dairy foods, includes whole grains, poultry, fish, and nuts, and is reduced in fats, red meat, sweets, and sugar-containing beverages. The 3 sodium levels are defined as higher (typical of current US consumption), intermediate (reflecting the upper limit of current US recommendations), and lower (reflecting potentially optimal levels). Participants are randomly assigned to 1 of the 2 dietary patterns using a parallel group design and are fed each of the 3 sodium levels using a randomized crossover design. The study provides participants with all of their food during a 2-week run-in feeding period and three 30-day intervention feeding periods. Participants attend the clinic for 1 meal per day, 5 days per week, and take home food for other meals. Weight is monitored and individual energy intake adjusted to maintain baseline weight. The primary outcome is systolic blood pressure measured at the end of each intervention feeding period. Systolic blood pressure is compared across the 3 sodium levels within each diet and across the 2 diets within each sodium level. If effects previously observed in clinical trials are additive, sodium reduction and the DASH diet together may lower blood pressure to an extent not as yet demonstrated for nonpharmacologic treatment. The DASH-Sodium results will have important implications for the prevention and treatment of high blood pressure.

Chromosome abnormalities in ovarian adenocarcinoma: I. Nonrandom chromosome abnormalities from 244 cases.

Cytogenetics provides important insights into the molecular pathogenesis of human cancers. Although extensive data exist on recurring cytogenetic abnormalities in hematologic cancers, data on individual solid tumor types remain limited. Previous studies of ovarian carcinoma indicated the presence of multiple, complex clonal chromosome abnormalities. Cytogenetics remains one of a few techniques capable of detecting these multiple, simultaneously occurring genetic abnormalities. We describe cytogenetic abnormalities from a series of 244 primary ovarian cancer specimens referred to a single institution. A total of 201/244 cases had fully characterized clonal chromosome abnormalities, of which 134 showed clonal chromosome breakpoints. We used a novel statistical technique to detect nonrandom chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints was detected at regions 1p1*, 1q1*, 1p2*, 1q2*, 1p3*, 1q3, 3p1*, 1q4*, 6q1*, 6p2, 6q2, 7p1*, 7q1, 7p2*, 11p1*, 11q1, 11q2*, 12p1, 12q2*, 13p1, and 19q1. Simultaneous occurrence of multiple abnormalities was common. However, 120/134 cases had breakpoints at one or more of 13 commonly involved regions (*), suggesting a hierarchy of genetic abnormalities. Among clinical and tumor variables that predict patient survival, tumor grade was significantly associated with the presence of chromosome breakpoints. In additional studies, we show that nonrandom chromosome abnormalities are associated with impaired survival in ovarian cancer and that specific, nonrandomly involved chromosome regions retain significant effects on survival when analyses are controlled for important clinical variables. Additional specific chromosome abnormalities in this series are described, including chromosome gains and losses in near‐diploid cases and homogeneously staining regions. These results suggest that recurring, nonrandom chromosome abnormalities are important in the pathogenesis and/or progression of ovarian cancers, and target areas of the genome for molecular genetic studies. Genes Chromosomes Cancer 25:290–300, 1999.