Using HbA1c to improve efficacy of the American Diabetes Association fasting plasma glucose criterion in screening for new type 2 diabetes in American Indians. The Strong Heart Study

WSTĘP. Celem badania jest określenie optymalnej krytycznej linii FPG-HbA1c, umożliwiającej rozpoznanie cukrzycy w grupie chorych z nieprawidłowym stężeniem glukozy na czczo (IFG, impaired fasting glucose) i poprawa skuteczności oznaczenia glikemii na czczo (FPG, fasting plasma glucose), stosowanego jako samodzielne badanie przesiewowe w kierunku cukrzycy u Indian amerykańskich. MATERIAŁ I METODY. Analizowano oznaczenia stężenia glukozy na czczo i 2 godziny po doustnym obciążeniu glukozą (2hPG) oraz HbA1c w grupie 2389 Indian amerykańskich w wieku 45-74 lat, którzy dotychczas nie byli leczeni z powodu cukrzycy, u których wcześniej nie rozpoznawano cukrzycy, a których poddano wyjściowej i powtórnej ocenie w ramach badania SHS (Strong Heart Study). Zgodnie z kryteriami American Diabetes Association cukrzycę rozpoznawano, gdy stężenie glukozy na czczo było równe lub wyższe niż 126 mg/dl lub gdy wartość 2hPG wynosiła 200 mg/dl lub więcej. Nieprawidłowe stężenie glukozy na czczo rozpoznawano, gdy mieściło się ono w przedziale 110 Ł FPG < 126 mg/dl, a jako wartość prawidłową (NFG, normal fasting glucose) przyjęto stężenie glukozy na czczo niższe niż 110 mg/dl. Do rozpoznawania cukrzycy w grupie badanych z IFG (2hPG ł 200 mg/dl) zastosowano modele regresji logistycznej. Najlepszy model wybrano na podstawie porównania pól pod krzywymi ROC (receiver operating characteristic) utworzonymi w oparciu o różne modele regresji logistycznej. Do wyznaczenia optymalnych wartości krytycznych użyto funkcji przydatności opartej na najlepszym modelu oraz współczynniku koszt/korzyść. Dane z drugiego badania wykorzystano do oceny wpływu czasu, jaki upłynął pomiędzy dwoma kolejnymi badaniami przesiewowymi, zarówno na kryterium FPG, jak i na optymalną krytyczną linię FPG-HbA1c. WYNIKI. W grupie chorych z nowo rozpoznaną cukrzycą, u 37% w badaniu wyjściowym oraz u 55,2% w badaniu powtórnym stwierdzono wartości 2hPG większe bądź równe 200 mg/dl, przy wartościach FPG mniejszych niż 126 mg/dl. Zarówno w wyjściowym, jak i w drugim oznaczeniu u znacznej części pacjentów z IFG rozpoznano cukrzycę (odpowiednio: 19,3 i 22,9%). Porównanie pól pod krzywymi ROC dla poszczególnych modeli regresji logistycznej wykazało, że największa wartość pola odpowiada łącznemu oznaczeniu FPG i HbA1c. Wartość ta była znamiennie wyższa od wartości pola dla oznaczenia FPG (p = 0,0008). Dla współczynnika koszt/korzyść = 0,23888 optymalna linia krytyczna o największej użyteczności miała wartość równą 0,89 × HbA1c + 0,11 × FPG = 17,92. U chorych, u których wartości FPG i HbA1c znajdowały się na tej linii lub powyżej, zalecano wykonanie doustnego testu tolerancji glukozy (OGTT, oral glucose tolerance test) w celu rozpoznania lub wykluczenia cukrzycy. Optymalne wartości krytyczne w badaniu powtórzonym po 4 latach były mniejsze. WNIOSKI. Według kryteriów American Diabetes Association cukrzycę rozpoznaje się, gdy wartość FPG jest większa lub równa 126 mg/dl albo gdy wartość 2hPG wynosi 200 mg/dl lub więcej. Wykonanie badania FPG jest proste i zaleca się je jako badanie przesiewowe. Natomiast stosowanie w praktyce OGTT w celu uzyskania wartości 2hPG jest kłopotliwe, szczególnie u chorych, u których stwierdza się wartość FPG poniżej 126 mg/dl. Wykonywanie OGTT jako badania przesiewowego u każdego pacjenta również jest niepraktyczne. Uzyskane dane wskazują, że u 37% osób z nowo wykrytą cukrzycą w badaniu wyjściowym i u 55,2% w oznaczeniu drugim stężenie glukozy w OGTT wynosiło 200 mg/dl lub więcej, podczas gdy wartość FPG była niższa niż 126 mg/dl. W takich wypadkach, na podstawie oznaczenia wyłącznie FPG jako badania przesiewowego, cukrzyca nie zostałaby rozpoznana. Mimo że odsetek chorych na cukrzycę w grupie NFG jest mały i może zostać zignorowany (4,7% w pierwszym i 6,5% w drugim oznaczeniu), to częstość przypadków cukrzycy stwierdzonych w grupie IFG w trakcie niniejszego badania (ok. 20%) wymaga uwzględnienia w dyskusji na temat metody badań przesiewowych. Wydaje się, że u części chorych z nieprawidłowym stężeniem glukozy na czczo, wybranych na podstawie optymalnych krytycznych wartości FPG-HbA1c, warto wykonać OGTT. Wyznaczenie optymalnej linii krytycznej i odstępu między kolejnymi testami przesiewowymi wymaga dalszych badań.INTRODUCTION. To find an optimal critical line in the fasting plasma glucose (FPG)-HbA1c plane for identifying diabetes in participants with impaired fasting glucose (IFG) and thereby improve the efficacy of using FPG alone in diabetes screening among American Indians. RESEARCH DESIGN AND METHODS. We used FPG, 2-h postload glucose (2hPG), and HbA1c measured in the 2,389 American Indians (aged 45&#8211;74 years, without diabetes treatment or prior history of diabetes) in the Strong Heart Study (SHS) baseline (second) examination. Participants were classified as having diabetes if they had either FPG &#163; 126 mg/dl or 2hPG &#8805; 200 mg/dl, as having IFG if they had 110 &#163; FPG < 126 mg/dl, and as having normal fasting glucose (NFG) if they had FPG < 110, according to the American Diabetes Association (ADA) definition. Logistic regression models were used for identifying diabetes (2hPG &#8805; 200 mg/dl) in IFG participants. The areas under the receiver operating characteristic (ROC) curves generated by different logistic regression models were evaluated and compared to select the best model. A utility function based on the best model and the cost-to-benefit ratio was used to find the optimal critical line. The data from the second examination were used to study the effect of the time interval between the successive diabetes screenings on both the FPG criterion and the optimal critical line. RESULTS. A total of 37% of all subjects with new diabetes at baseline and 55.2% of those in the second exam had 2hPG &#8805; 200 but FPG < 126. There was a very large portion of IFG participants with diabetes (19.3 and 22.9% in the baseline and second exam, respectively). Among the areas under the ROC curves, the area generated by the logistic regression model on FPG plus HbA1c is the largest and is significantly larger than that based on FPG (P = = 0.0008). For a cost-to-benefit ratio of 0.23888, the optimal critical line that has the highest utility is: 0.89 × HbA1c + 0.11 × FPG = 17.92. Those IFG participants whose FPG and HbA1c were above or on the line were referred to take an oral glucose tolerance test (OGTT) to diagnose diabetes. The optimal critical line is lower if a successive diabetes screening will be conducted 4 years after the previous screening. CONCLUSIONS. FPG &#8805; 126 and 2hPG &#8805; 200, as suggested by the ADA, are used in-dependently to define diabetes. The FPG level is easy to obtain, and using FPG alone is suggested for diabetes screening. It is difficult to get physicians and patients to perform an OGTT to get a 2hPG level because of the many drawbacks of the OGTT, especially in those patients who already have FPG < 126. It is also impractical to conduct an OGTT for everyone in a diabetes screening. Our data show that 37% of all subjects with new diabetes in the SHS baseline exam and 55.2% of those in the second exam have 2hPG &#8805; 200 but FPG < 126. These cases of diabetes cannot be detected if FPG is used alone in a diabetes screening. Therefore, although the small portion of diabetes in the NFG group (4.7% in the base-line and 6.9% in the second exam) may be ignored, those cases of diabetes among IFG participants (~20% in our data) need further consideration in a diabetes screening. It may be worthwhile for those IFG participants identified by the optimal critical line to take an OGTT. The optimal critical line and time interval between successive diabetes screenings need further study

Risk Factors for Arterial Hypertension in Adults With Initial Optimal Blood Pressure

Whether metabolic factors and their change over time influence development of arterial hypertension in adults with initially optimal blood pressure (BP) is unknown. We analyzed associations of BP in the optimal range (<120/80 mm Hg), metabolic risk factors, and their changes over 4-year follow-up, with 8-year incident hypertension, in a cohort of American Indians with a high prevalence of obesity. At baseline, 967 participants with optimal BP and no prevalent cardiovascular disease (69.5% women; mean age, 54±7 years) were evaluated and reexamined after 4 (second examination) and 8 years to evaluate predictors of 8-year incident arterial hypertension. In participants with normal glucose tolerance, baseline BP and decrease in high-density lipoprotein cholesterol from baseline to the second examination were the most potent predictors of 8-year arterial hypertension (both P <0.0001), with additional effects of baseline waist circumference and its increase, increase in BP, and presence of diabetes at the second examination (all P <0.04). In participants with impaired glucose tolerance or diabetes, the most potent predictor of 8-year incident hypertension was diabetes at the second examination ( P <0.0001) followed by a increase in BP and LDL cholesterol over the first 4 years (both P <0.001). Thus, incident arterial hypertension can be predicted by initial metabolic profile and unfavorable metabolic variations over time, in addition to initial BP. At optimal levels of initial BP, increasing abdominal obesity, and abnormal lipid profile are major predictors of development of arterial hypertension. Possible implications of these findings for primary cardiovascular prevention should be tested in prospective studies

The Zuni Kidney Project

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Tobacco Use and Cardiovascular Disease among American Indians: The Strong Heart Study

Tobacco use among American Indians has a long and complicated history ranging from its utilization in spiritual ceremonies to its importance as an economic factor for survival. Despite this cultural tradition and long history, there are few studies of the health effects of tobacco in this population. The Strong Heart Study is a prospective observational study of cardiovascular disease (CVD) in 13 American Indian tribes in Arizona, Oklahoma, and North and South Dakota with 4,549 participants. Baseline examinations were followed by two examinations at regular intervals and 16 years of morbidity and mortality follow-up. Hazard ratios (HRs) for non-fatal CVD for current smokers vs. non-smokers after adjusting for other risk factors were significant in women (HR = 1.94, 95% CI 1.54 to 2.45) and men (HR = 1.59, 95% CI 1.16 to 2.18). Hazard ratios for fatal CVD for current smokers vs. non-smokers after adjusting for other risk factors were significant in women (HR = 1.64, 95% CI 1.04 to 2.58), but not in men. Individuals who smoked and who were diagnosed with diabetes mellitus, hypertension or renal insufficiency were more likely to quit smoking than those without these conditions. On average, American Indians smoke fewer cigarettes per day than other racial/ethnic groups; nevertheless, the ill effects of habitual tobacco use are evident in this population

Health Facility Characteristics and Their Relationship to Coverage of PMTCT of HIV Services across Four African Countries: The PEARL Study

Background: Health facility characteristics associated with effective prevention of mother-to-child transmission of HIV (PMTCT) coverage in sub-Saharan are poorly understood. Methodology/Principal Findings: We conducted surveys in health facilities with active PMTCT services in Cameroon, Cote d’Ivoire, South Africa, and Zambia. Data was compiled via direct observation and exit interviews. We constructed composite scores to describe provision of PMTCT services across seven topical areas: antenatal quality, PMTCT quality, supplies available, patient satisfaction, patient understanding of medication, and infrastructure quality. Pearson correlations and Generalized Estimating Equations (GEE) to account for clustering of facilities within countries were used to evaluate the relationship between the composite scores, total time of visit and select individual variables with PMTCT coverage among women delivering. Between July 2008 and May 2009, we collected data from 32 facilities; 78 % were managed by the government health system. An opt-out approach for HIV testing was used in 100 % of facilities in Zambia, 63 % in Cameroon, and none in Côte d’Ivoire or South Africa. Using Pearson correlations, PMTCT coverage (median of 55%, (IQR: 33–68) was correlated with PMTCT quality score (rho = 0.51; p = 0.003); infrastructure quality score (rho = 0.43; p = 0.017); time spent at clinic (rho = 0.47

Hepatitis B, HIV, and Syphilis Seroprevalence in Pregnant Women and Blood Donors in Cameroon

Objectives. We estimated seroprevalence and correlates of selected infections in pregnant women and blood donors in a resourcelimited setting. Methods. We performed a cross-sectional analysis of laboratory seroprevalence data from pregnant women and voluntary blood donors from facilities in Cameroon in 2014. Rapid tests were performed to detect hepatitis B surface antigen, syphilis treponemal antibodies, and HIV-1/2 antibodies. Blood donations were also tested for hepatitis C and malaria. Results. The seroprevalence rates and ranges among 7069 pregnant women were hepatitis B 4.4% (1.1-9.6%), HIV 6% (3.0-10.2%), and syphilis 1.7% (1.3-3.8%) with significant variability among the sites. Correlates of infection in pregnancy in adjusted regression models included urban residence for hepatitis B (aOR 2.9, CI 1.6-5.4) and HIV (aOR 3.5, CI 1.9-6.7). Blood donor seroprevalence rates and ranges were hepatitis B 6.8% (5.0-8.8%), HIV 2.2% (1.4-2.8%), syphilis 4% (3.3-4.5%), malaria 1.9%, and hepatitis C 1.7% (0.5-2.5%). Conclusions. Hepatitis B, HIV, and syphilis infections are common among pregnant women and blood donors in Cameroon with higher rates in urban areas. Future interventions to reduce vertical transmission should include universal screening for these infections early in pregnancy and provision of effective prevention tools including the birth dose of univalent hepatitis B vaccine

THE ABERDEEN INDIAN HEALTH SERVICE INFANT MORTALITY STUDY: DESIGN, METHODOLOGY, AND IMPLEMENTATION

Abstract: Of all India

Measuring coverage in MNCH: population HIV-free survival among children under two years of age in four African countries

BACKGROUND: Population-based evaluations of programs for prevention of mother-to-child HIV transmission (PMTCT) are scarce. We measured PMTCT service coverage, regimen use, and HIV-free survival among children ≤24 mo of age in Cameroon, Côte D'Ivoire, South Africa, and Zambia. Methods and FINDINGS: We randomly sampled households in 26 communities and offered participation if a child had been born to a woman living there during the prior 24 mo. We tested consenting mothers with rapid HIV antibody tests and tested the children of seropositive mothers with HIV DNA PCR or rapid antibody tests. Our primary outcome was 24-mo HIV-free survival, estimated with survival analysis. In an individual-level analysis, we evaluated the effectiveness of various PMTCT regimens. In a community-level analysis, we evaluated the relationship between HIV-free survival and community PMTCT coverage (the proportion of HIV-exposed infants in each community that received any PMTCT intervention during gestation or breastfeeding). We also compared our community coverage results to those of a contemporaneous study conducted in the facilities serving each sampled community. Of 7,985 surveyed children under 2 y of age, 1,014 (12.7%) were HIV-exposed. Of these, 110 (10.9%) were HIV-infected, 851 (83.9%) were HIV-uninfected, and 53 (5.2%) were dead. HIV-free survival at 24 mo of age among all HIV-exposed children was 79.7% (95% CI: 76.4, 82.6) overall, with the following country-level estimates: Cameroon (72.6%; 95% CI: 62.3, 80.5), South Africa (77.7%; 95% CI: 72.5, 82.1), Zambia (83.1%; 95% CI: 78.4, 86.8), and Côte D'Ivoire (84.4%; 95% CI: 70.0, 92.2). In adjusted analyses, the risk of death or HIV infection was non-significantly lower in children whose mothers received a more complex regimen of either two or three antiretroviral drugs compared to those receiving no prophylaxis (adjusted hazard ratio: 0.60; 95% CI: 0.34, 1.06). Risk of death was not different for children whose mothers received a more complex regimen compared to those given single-dose nevirapine (adjusted hazard ratio: 0.88; 95% CI: 0.45, 1.72). Community PMTCT coverage was highest in Cameroon, where 75 of 114 HIV-exposed infants met criteria for coverage (66%; 95% CI: 56, 74), followed by Zambia (219 of 444, 49%; 95% CI: 45, 54), then South Africa (152 of 365, 42%; 95% CI: 37, 47), and then Côte D'Ivoire (3 of 53, 5.7%; 95% CI: 1.2, 16). In a cluster-level analysis, community PMTCT coverage was highly correlated with facility PMTCT coverage (Pearson's r  = 0.85), and moderately correlated with 24-mo HIV-free survival (Pearson's r  = 0.29). In 14 of 16 instances where both the facility and community samples were large enough for comparison, the facility-based coverage measure exceeded that observed in the community. CONCLUSIONS: HIV-free survival can be estimated with community surveys and should be incorporated into ongoing country monitoring. Facility-based coverage measures correlate with those derived from community sampling, but may overestimate population coverage. The more complex regimens recommended by the World Health Organization seem to have measurable public health benefit at the population level, but power was limited and additional field validation is needed. Please see later in the article for the Editors' Summar

Measurement of Leptonic Asymmetries and Top Quark Polarization in ttbar Production

We present measurements of lepton (l) angular distributions in ttbar -> W+ b W- b -> l+ nu b l- nubar bbar decays produced in ppbar collisions at a center-of-mass energy of sqrt(s)=1.96TeV, where l is an electron or muon. Using data corresponding to an integrated luminosity of 5.4fb^-1, collected with the D0 detector at the Fermilab Collider, we find that the angular distributions of l- relative to anti-protons and l+ relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry A^l_FB = (5.8 +- 5.1(stat) +- 1.3(syst))%, compared to the standard model prediction of A^l_FB (predicted) = (4.7 +- 0.1)%. This result is further combined with the measurement based on the analysis of the l+jets final state to obtain A^l_FB = (11.8 +- 3.2)%. Furthermore, we present a first study of the top-quark polarization.Comment: submitted versio