Perinatal periods of risk: phase 2 analytic methods for further investigating feto-infant mortality.

The perinatal periods of risk (PPOR) methods provide a framework and tools to guide large urban communities in investigating their feto-infant mortality problem. The PPOR methods have 11 defined steps divided into three analytic parts: (1) Analytic Preparation; (2) Phase 1 Analysis-identifying the opportunity gaps or populations and risk periods with largest excess mortality; and (3) Phase 2 Analyses-investigating these opportunity gaps. This article focuses on the Phase 2 analytic methods, which systematically investigate the opportunity gaps to discover which risk and preventive factors are likely to have the largest effect on improving a community's feto-infant mortality rate and to provide additional information to better direct community prevention planning. This article describes the last three PPOR epidemiologic steps for investigating identified opportunity gaps: identifying the mechanism for excess mortality; estimating the prevalence of risk and preventive factors; and estimating the impact of these factors. While the three steps provide a common strategy, the specific analytic details are tailored for each of the four perinatal risk periods. This article describes the importance, prerequisites, alternative approaches, and challenges of the Phase 2 methods. Community examples of the methods also are provided.

Perinatal periods of risk: analytic preparation and phase 1 analytic methods for investigating feto-infant mortality.

The Perinatal Periods of Risk (PPOR) methods provide the necessary framework and tools for large urban communities to investigate feto-infant mortality problems. Adapted from the Periods of Risk model developed by Dr. Brian McCarthy, the six-stage PPOR approach includes epidemiologic methods to be used in conjunction with community planning processes. Stage 2 of the PPOR approach has three major analytic parts: Analytic Preparation, which involves acquiring, preparing, and assessing vital records files; Phase 1 Analysis, which identifies local opportunity gaps; and Phase 2 Analyses, which investigate the opportunity gaps to determine likely causes of feto-infant mortality and to suggest appropriate actions. This article describes the first two analytic parts of PPOR, including methods, innovative aspects, rationale, limitations, and a community example. In Analytic Preparation, study files are acquired and prepared and data quality is assessed. In Phase 1 Analysis, feto-infant mortality is estimated for four distinct perinatal risk periods defined by both birthweight and age at death. These mutually exclusive risk periods are labeled Maternal Health and Prematurity, Maternal Care, Newborn Care, and Infant Health to suggest primary areas of prevention. Disparities within the study community are identified by comparing geographic areas, subpopulations, and time periods. Excess mortality numbers and rates are estimated by comparing the study population to an optimal reference population. This excess mortality is described as the opportunity gap because it indicates where communities have the potential to make improvement.

Bone mineral density-affecting genes in Africans.

BACKGROUND: We have recently reported the role of environmental exposure in the ethnic diversity of bone mineral density (BMD). Potential genetic difference has not been adequately assessed. PURPOSE: To determine allele frequencies of BMD-affecting genes and their association with BMD in Africans. METHODS: Allele frequencies at 18 polymorphic sites in 13 genes that affect BMD in Asians and/or Caucasians were determined in 143 recent immigrants (55 men and 88 women, 18-51 years of age) from sub-Saharan Sudan to the United States. Genetic association studies were performed. RESULTS: Among the 14 single-nucleotide polymorphisms (SNPs), 10 were significantly different in allele frequency between Sudanese and Asians, and 10 between Sudanese and Caucasians. Only the osteocalcin gene was not significantly different in allele frequency among Sudanese, Asians and Caucasians. Allele frequencies in the TGFB, COL1A1 and CSR genes were extremely low (<0.04) in the Sudanese. Frequencies of microsatellite alleles in four genes were significantly different among Sudanese, Asians and Caucasians. SNPs in the VDR and ERalpha genes were associated with BMD and/or BMC (bone mineral content) at several bone sites. CONCLUSIONS: Genetic difference may play a role in the ethnic diversity in BMD and/or BMC.

Bone mineral density of recent African immigrants in the United States.

BACKGROUND: Racial/ethnic difference in bone mineral density (BMD) exists. The underlying mechanism is unclear and needs investigation. PURPOSE: To determine BMD and its relation to environmental exposure in recent African immigrants. METHODS: BMD in recent sub-Saharan Sudanese immigrants (55 men and 88 premenopausal women) in the United States was measured. Analysis of covariance (ANCOVA) model was performed, with total body, spine and hip BMD as dependent variables; and sex, age, body weight, the length of stay in the United States, and milk intake as independent variables. RESULTS: BMD Z score in the spine but not total body or hip in the Sudanese immigrants was significantly lower compared with the normative values of African Americans and Caucasians. Total body and hip BMD was positively correlated (p < 0.015) with their length of stay in the United States. Hip BMD was significantly correlated with milk intake (p < 0.02) and marginally (p = 0.052) with their length of stay in the United States, independent of body weight. CONCLUSIONS: Spinal BMD was significantly lower in recent Sudanese immigrants than in African Americans or Caucasians. Their hip and total body BMD was associated with their length of stay in the United States, suggesting a potential environmental factors in the ethnic diversity of BMD.

The effect of soy protein isolate on bone metabolism.

OBJECTIVE: This double-blind, 15-month pilot study was designed to investigate the effect of soy protein isolate with varying concentrations of isoflavones on early postmenopausal bone loss and lipids. DESIGN: A total of 65 women, with a mean age of 55 years and 7.5 years since menopause, were randomized to one of three groups; soy protein with 96 mg isoflavones/day, soy with 52 mg isoflavones/day, or soy without isoflavones (< 4 mg isoflavones/day). Soy was given for 9 months and then discontinued; participants were followed for an additional 6 months. Bone mineral density (BMD) and blood lipids were measured during this time. RESULTS: Measurement of serum isoflavones at 3 months showed dose-related increases in the three groups. There was no significant effect of the soy supplements on BMD of the spine or femoral neck in any of the three groups. BMD increased significantly in the trochanter at 9 months (P = 0.0219) and at 15 months (P < 0.05) in the group given isoflavone-free soy compared with the other two groups. There was no significant effect of soy on lipid metabolism at the end of the intervention. CONCLUSION: The present study did not find a significant positive effect of soy protein isolate supplemented with isoflavones on BMD and the serum lipid profile in early postmenopausal women.

Long-term follow-up of primary glaucoma surgery with Ahmed glaucoma valve implant versus trabeculectomy.

PURPOSE: To compare the long-term results of trabeculectomy and Ahmed glaucoma valve implant in the initial surgical management of primary open- and closed-angle glaucoma. DESIGN: Randomized controlled clinical trial. METHODS: One eye each of consecutive patients with primary glaucoma and without prior intraocular surgery was randomized to receive either trabeculectomy or the Ahmed implant. Large university-affiliated eye hospital in Columbo, Sri Lanka. RESULTS: Of 123 patients, 64 were randomized to trabeculectomy and 59 to the Ahmed implant. With a mean follow-up of 31 months, the trabeculectomy group had statistically lower intraocular pressures (IOP) during the first postoperative year. After the first year, the IOPs were comparable. No statistically significant differences between groups were noted for postoperative visual acuity, visual field, anterior chamber depth, and short-term or long-term complications. Adjunctive medication requirement was comparable for both groups. The cumulative probabilities of success (IOP <21 mm Hg and at least 15% reduction in IOP from preoperative levels) at the final follow-up period (months, 41-52) were 68.1% for trabeculectomy and 69.8% for Ahmed implant (P =.86). CONCLUSIONS: Lower IOPs were noted for the trabeculectomy group during the first year. With longer follow-up, the IOPs and the cumulative probabilities of success were comparable between the two groups.

Protein intake: effects on bone mineral density and the rate of bone loss in elderly women.

BACKGROUND: The role of dietary protein in bone metabolism is controversial. OBJECTIVE: We investigated the associations of dietary protein intake with baseline bone mineral density (BMD) and the rate of bone loss over 3 y in postmenopausal elderly women. DESIGN: Women aged 65-77 y (n = 489) were enrolled in an osteoporosis intervention trial. We studied the associations of protein intake as a percentage of energy with baseline BMD and the rate of bone loss in 96 women in the placebo group (n = 96). We also examined the effect of the interaction of dietary calcium intake with protein intake on BMD. RESULTS: In the cross-sectional study, a higher intake of protein was associated with higher BMD. BMD was significantly higher (P < 0.05) in the spine (7%), midradius (6%), and total body (5%) in subjects in the highest quartile of protein intake than in those in the lower 2 quartiles. This positive association was seen in women with calcium intakes > 408 mg/d. There was no significant effect of protein intake on hip BMD. In the longitudinal study of the placebo group, there was no association between protein intake and the rate of bone loss. CONCLUSIONS: The highest quartile of protein intake (: 72 g/d) was associated with higher BMD in elderly women at baseline only when the calcium intake exceeded 408 mg/d. In the longitudinal study, no association was seen between protein intake and the rate of bone loss, perhaps because the sample size was too small or the follow-up period of 3 y was not long enough to detect changes.

Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women.

Seasonal variation of serum vitamin D metabolites, PTH, bone turnover markers, and bone mineral density (BMD), adjusted for confounding variables, was studied in a cross-sectional population of 251 ambulatory elderly women aged 65-77 yr. A significant (P < 0.05) seasonal change was observed in serum 25 hydroxyvitamin D (25OHD), bone resorption marker (urine N-telopeptide), and BMD of the spine, total body, and mid-radius. Serum 25OHD was significantly lower (P < 0.05) in winter (December, January, February, March) compared with summer (June, July, August, September), with the nadir in February (68.4 +/- 6.74 nmol/liter) and the zenith in August (85.6 +/- 5.12 nmol/liter). Mean serum PTH levels were higher in winter when serum 25OHD was low, and mean serum PTH was lower in summer when serum 25OHD was high, although the seasonal change in serum PTH was not significant. The change in serum 1,25-dihydroxy vitamin D(3) paralleled that of serum 25OHD levels, but the seasonal effect was not significant. Mean 24-h urine N-telopeptide showed a significant seasonal change (P < 0.05); it was about 24% higher in February (zenith) compared with that in August (nadir). The zenith month of urine N-telopeptide levels corresponded to the nadir month of serum 25OHD levels and vice versa. A significant (P < 0.05) inverse correlation was observed between 24-h urine N-telopeptides and serum 25OHD levels. There was a significant (P < 0.05) seasonal change in mean BMD of spine, total body, and mid-radius. These changes paralleled those in serum 25OHD levels. Spine BMD was 8.4% higher in August (zenith) compared with that in February (nadir), whereas total body BMD and mid-radius BMD were 6.1 and 7.6% higher, respectively, in July (zenith) compared with that in January (nadir). There was a nonsignificant increase of 3.6% in total hip BMD. In summary (see Fig. 5), the seasonal changes in vitamin D metabolism in elderly women are closely associated with small changes in serum PTH, changes in bone resorption, and BMD.

THE DETERMINATION OF GENETIC COVARIANCES AND PREDICTION OF EVOLUTIONARY TRAJECTORIES BASED ON A GENETIC CORRELATION MATRIX.

There is much interest in measuring selection, quantifying evolutionary constraints, and predicting evolutionary trajectories in natural populations. For these studies, genetic (co)variances among fitness traits play a central role. We explore the conditions that determine the sign of genetic covariances and demonstrate a critical role of selection in shaping genetic covariances. In addition, we show that genetic covariance matrices rather than genetic correlation matrices should be characterized and studied in order to infer genetic basis of population differentiation and/or to predict evolutionary trajectories.