Community-wide cardiovascular disease prevention programs and health outcomes in a rural county, 1970-2010.

IMPORTANCE: Few comprehensive cardiovascular risk reduction programs, particularly those in rural, low-income communities, have sustained community-wide interventions for more than 10 years and demonstrated the effect of risk factor improvements on reductions in morbidity and mortality. OBJECTIVE: To document health outcomes associated with an integrated, comprehensive cardiovascular risk reduction program in Franklin County, Maine, a low-income rural community. DESIGN, SETTING, AND PARTICIPANTS: Forty-year observational study involving residents of Franklin County, Maine, a rural, low-income population of 22,444 in 1970, that used the preceding decade as a baseline and compared Franklin County with other Maine counties and state averages. INTERVENTIONS: Community-wide programs targeting hypertension, cholesterol, and smoking, as well as diet and physical activity, sponsored by multiple community organizations, including the local hospital and clinicians. MAIN OUTCOMES AND MEASURES: Resident participation; hypertension and hyperlipidemia detection, treatment, and control; smoking quit rates; hospitalization rates from 1994 through 2006, adjusted for median household income; and mortality rates from 1970 through 2010, adjusted for household income and age. RESULTS: More than 150,000 individual county resident contacts occurred over 40 years. Over time, as cardiovascular risk factor programs were added, relevant health indicators improved. Hypertension control had an absolute increase of 24.7% (95% CI, 21.6%-27.7%) from 18.3% to 43.0%, from 1975 to 1978; later, elevated cholesterol control had an absolute increase of 28.5% (95% CI, 25.3%-31.6%) from 0.4% to 28.9%, from 1986 to 2010. Smoking quit rates improved from 48.5% to 69.5%, better than state averages (observed - expected [O - E], 11.3%; 95% CI, 5.5%-17.7%; P < .001), 1996-2000; these differences later disappeared when Maine's overall quit rate increased. Franklin County hospitalizations per capita were less than expected for the measured period, 1994-2006 (O - E, -17 discharges/1000 residents; 95% CI -20.1 to -13.9; P < .001). Franklin was the only Maine county with consistently lower adjusted mortality than predicted over the time periods 1970-1989 and 1990-2010 (O - E, -60.4 deaths/100,000; 95% CI, -97.9 to -22.8; P < .001, and -41.6/100,000; 95% CI, -77.3 to -5.8; P = .005, respectively). CONCLUSIONS AND RELEVANCE: Sustained, community-wide programs targeting cardiovascular risk factors and behavior changes to improve a Maine county's population health were associated with reductions in hospitalization and mortality rates over 40 years, compared with the rest of the state. Further studies are needed to assess the generalizability of such programs to other US county populations, especially rural ones, and to other parts of the world.

A systematic review and economic evaluation of the clinical effectiveness and cost-effectiveness of aldosterone antagonists for postmyocardial infarction heart failure.

BACKGROUND: Two aldosterone inhibitors are currently licensed for heart failure (HF) in the UK: spironolactone and eplerenone. Recent clinical guidelines recommend eplerenone after an acute myocardial infarction (MI) for patients with symptoms and/or signs of HF and left ventricular dysfunction. OBJECTIVES: The primary objective was to evaluate relative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone in patients with postMI HF and explore the possibility of conducting an indirect comparison of spironolactone and eplerenone. A second objective was to undertake value-of-information (VOI) analyses to determine the need for further research to identify research questions critical to decision-making and to help inform the design of future studies. DATA SOURCES: Relevant databases including MEDLINE, EMBASE and CENTRAL were searched between September and December 2008. Randomised controlled trials (RCTs) of spironolactone, eplerenone, canrenone or potassium canrenoate were included if conducted in a postMI HF population. Trials of general HF patients with a subgroup of postMI HF patients were considered if they had at least 100 ischaemic participants per arm and the authors provided subgroup data when contacted. Adverse events summary data were sought from recognised reference sources and RCTs or observational studies in any population that recruited more than 100 participants. REVIEW METHODS: The comparative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone was derived using Bayesian meta-regression drawing on a wider 'network' of aldosterone trials to those considered in the main clinical effectiveness review. An alternative scenario was also considered assuming a 'class effect' for the aldosterone antagonists in terms of major clinical events, but allowing for potential differences in side effect profiles. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs) where appropriate. Uncertainty in cost-effectiveness results was also presented and used to inform future research priorities using VOI analyses based on expected value of perfect information (EVPI). A probabilistic decision analytic model was developed to estimate cost-effectiveness of spironolactone, eplerenone and standard care for management of postMI HF, provide estimates relevant to the NHS and explore alternative approaches to an indirect comparison between spironolactone and eplerenone. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the NHS persepctive. In the base-case analysis, 2-year treatment duration was assumed, consistent with the follow-up in the main RCTs. Other scenarios were explored to examine the robustness of alternative assumptions including impact of different treatment durations. RESULTS: Searches yielded five RCTs: two spironolactone trials of poor methodological quality and three trials of which only one (of eplerenone) specifically examined postMI HF (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study, EPHESUS). One trial of spironolactone (Randomised Aldactone Evaluation Study, RALES) and one of canrenone (Antiremodelling Effect of Aldosterone receptors blockade with canrenone In mild Chronic Heart Failure, AREA IN-CHF) comprised general HF, but data were available for an ischaemic subgroup. Structural similarity of spironolactone and eplerenone suggests that they may be interchangeable, but formal indirect comparison between the three trials was severely limited by trial differences. Relative safety data were limited from RCTs and observational sources. Hyperkalaemia rates varied, but were generally higher than for placebo; data were insufficient to assess discontinuation because of hyperkalaemia.Gynaecomastia rates were higher with spironolactone. Adverse event data were sparse. Systematic review of economic evidence identified three main published studies but none used a UK perspective or attempted to compare cost-effectiveness in postMI HF. The new decision model indicated that eplerenone was the most cost-effective strategy for postMI HF (ICER of eplerenone compared with standard care was 4457 pounds per QALY, increasing to 7893 pounds per QALY if treatment continued over the patient's lifetime); in neither scenario did spironolactone appear cost-effective. The ICER of eplerenone was consistently under the 20,000-30,000 pounds per QALY threshold used to establish value for money in the NHS. Uncertainty resulted in EVPI estimates between 820M pounds (base-case) and 1265M pounds (lifetime treatment duration scenario). When class effect for mortality and hospitalisations was assumed spironolactone emerged as the most cost-effective treatment and EVPI estimates were negligible. If class effect is considered more plausible than the results of the evidence synthesis model then there would be limited value in additional research. LIMITATIONS: Exchangeability between trials was poor and there was a lack of robust data in RCTs. CONCLUSIONS: Only two good-quality trials of aldosterone inhibitors in the postMI HF population were found, but lack of exchangeability with respect to study populations, meant that a comparison between these drugs could not be done. It consistently emerged that, compared with usual care, use of an aldosterone antagonist appears to be a highly cost-effective strategy for the management of postMI HF patients in the NHS. An adequately powered, well-conducted RCT that directly compares spironolactone and eplerenone is required to provide more robust evidence on the optimal management of postMI HF patients.

Assessment of fetal atrioventricular time intervals by tissue Doppler and pulse Doppler echocardiography: normal values and correlation with fetal electrocardiography.

OBJECTIVE: To establish gestational age-specific reference values of normal fetal atrioventricular (AV) time interval by spectral tissue Doppler imaging (TDI) and pulse-wave Doppler (PD) methods, and to assess their correlation with signal-averaged fetal PR intervals (ECG). DESIGN: Cohort study. SETTING: Tertiary centre for fetal cardiology. PATIENTS AND MEASURES: 131 pregnant women between 14 and 42 weeks' gestation underwent 196 fetal echocardiograms and 158 fetal ECG studies. TDI-derived AV intervals were measured as the intervals from atrial contraction (Aa) to isovolumic contraction (IV) and from Aa to ventricular systole (Sa) at the right ventricular free wall. PD-derived AV intervals were measured from simultaneous left ventricular inflow/outflow (in/out) and superior vena cava/aorta (V/AO) recordings. RESULTS: Measurements were possible by ECG in 61%, by TDI in 100%, by in/out in 100% and by V/AO in 97% of examinations. Aa-IV correlated significantly better with PR intervals (y = 0.67x + 38.29, R(2) = 0.15, p < 0.0001, mean bias 8.0 ms) than did in/out (R(2) = 0.10, p = 0.002, bias 18.7 ms) and V/AO (R(2) = 0.06, p = 0.02, bias 12.4 ms). Gestational age and AV intervals were positively correlated with all imaging modalities (R(2) = 0.19-0.31, p < 0.0001). CONCLUSION: This study showed the feasibility of fetal AV interval measurements by TDI, and established gestational age-specific reference data. TDI-derived Aa-IV intervals track ECG PR intervals more closely than PD-derived AV intervals and thus should be used as the ultrasound method of choice in assessing fetal AV conduction.

Comparison of the acute effects on gas exchange of nasal ventilation and doxapram in exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Nasal intermittent positive pressure ventilation (NIPPV) is useful in exacerbations of chronic obstructive pulmonary disease (COPD) complicated by ventilatory failure. The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure. METHODS: Patients admitted with acute exacerbations of COPD and type 2 respiratory failure (Pao2 < 8 kPa and PaCO2 > 6.7 kPa) who did not improve with conventional treatment were randomised to receive either NIPPV or intravenous doxapram. Blood gas tensions were monitored for four hours. RESULTS: In nine patients who received NIPPV the arterial PaO2 improved from a mean (SE) of 5.9 (0.4) kPa to a maximum of 8.1 (0.6) kPa which was maintained at four hours. Eight patients who received doxapram had a similar baseline Pao2 of 5.6 (0.4) kPa which rose to a maximum of 7.3 (0.5) kPa but this was not maintained at four hours. The improvement in Pao2 in patients on NIPPV was accompanied by a fall in Paco2 but, in contrast, in those who received doxapram there was no improvement in Paco2. CONCLUSIONS: NIPPV may be more effective than doxapram in the management of acute ventilatory failure complicating COPD.

Management information and self-governing NHS hospital trusts.

The proposal for self-governing hospital trusts within the NHS, announced in the White Paper Working for Patients on 31 January 1989 and enacted through passage of the National Health Service and Community Care Act 1990 last July, introduces free market incentives to NHS hospitals. Hospitals applying for self-governing status must first demonstrate that they have an information system appropriate to support decision making in the new context. An overall information systems flow and an approach to information systems development are recommended based upon the Freeman Hospital model. The Freeman Hospital is a national pilot site selected by the NHS Management Executive for development of information systems for NHS hospitals.

Detection of the ovulatory-luteinizing hormone surge with an enzyme-linked immunospecific human urinary luteinizing hormone assay: applicability to nonhuman primates.

Heterologous antibodies have frequently been used to develop assays in other species. Human urinary LH kits, widely available for predicting the LH surge, offer a unique opportunity to determine the timing of ovulation and mating in nonhuman primates. We tested three commercially available ovulation predictor kits for utility in two macaque species. Midfollicular, midcycle, and castrate urines and their corresponding serum samples were assessed for LH activity using established RIAs as well as urinary ovulation kits. Macaque LH did not sufficiently cross-react with the human urinary anti-LH antibodies in any of the predictor test kits. Although these kits offer excellent results in predicting ovulation by measurement of urinary LH in humans, they appear not to be applicable for urinary LH detection in rhesus nor cynomolgus macaques.

Maternal positioning to prevent or alleviate dystocia in labor.

Women have always used different positions to make labor more comfortable and, when allowed, spontaneously change position numerous times during labor and birth. The positions they choose, while dictated by comfort, frequently prove to be beneficial in promoting labor progress. For 50 years, the value of mobility and position change received little attention, but recent research and advances in the design of birthing equipment indicate that maternal positioning provides a valuable, noninvasive, and acceptable intervention. This paper reviewed six mechanisms by which dystocia may be prevented or corrected through the use of maternal positioning.

Maternal position during parturition in normal labor.

While controversy exists as to the relationship between maternal position in labor and such measures as the labor duration, subjective discomfort, and fetal outcome, little appears to be known about the positions women assume in labor when they are permitted to do so without coercion or instruction. To learn more about maternal position in labor, we observed 80 consecutive patients with uncomplicated normal spontaneous vaginal delivery over the course of labor to ascertain the positions volitionally chosen by each. Data were collected on position preferences and phase of labor. All labors were analyzed; a codified lexicon was established to describe the position pattern in each phase and the principal positions the patient assumed over the course of labor. The frequencies and distributions were determined for nulliparas and multiparas separately and rates of position change were assessed. It was found that gravidas chose a number of different principal positions in the early phases of labor, but that they became more narrowly selective in the deceleration phase and second stage; at the same time, they tended to change position more often in late labor.

Toxicity testing for human in vitro fertilization programs.

Using a mouse embryo culture system, several procedures and materials associated with human in vitro fertilization protocols were tested for potential toxicity. Also, quality-control assays were performed for media prepared by nine different human in vitro fertilization programs. Detrimental effects upon embryo development were observed when culture media were exposed to the following substances: surgical instruments sterilized with Cidex or Cidex-7 or sterilized with ethylene oxide after packaging in Nest Protector Packs, various brands of surgical gloves, and various synthetic materials being evaluated as possible needle or catheter "liners." Results from comparative testing of media and serum supplements prepared by different in vitro programs indicated a wide range in culture medium quality, as assayed by the ability of the reagents to support mouse embryo development. The importance of an animal model system available to all human in vitro programs for routine quality-control analysis and testing of novel uses of materials and innovative methods is discussed.

Production of prostaglandins by the pseudopregnant rat uterus, in vitro, and the effect of tamoxifen with the identification of 6-keto-prostaglandin F1alpha as a major product.

1 Prostaglandin production by rat uterus homogenates has been studied, in vitro, on days 2 to 13 of pseudopregnancy. 2 The highest production of prostaglandins occurred on day 5. 3 The amounts of prostaglandins F and D formed were higher than the amounts of prostaglandin E on every day studied. 4 The ratios of prostglandins F and D to prostaglandin E produced steadily decreased up to day 6. It then increased with the highest values occurring between days 10 and 13, 5 Progesterone levels in peripheral plasma increased rapidly from days 2 to 5, remained high up to day 9, then steadily decreased between days 10 and 13. 6 The anti-oestrogenic drug, tamoxifen administered on day 2, significantly inhibited the increase of prostaglandin production which occurred on day 5. Prostaglandin E production was inhibited more than the production of prostaglandins F and D. 7 Analysis of the uterine extracts by gas chromatography and mass spectrometry showed prostaglandin F2alpha, F1alpha (in trace amounts), E2 and D2 to be present. 8 The major product detected was 6-keto-prostaglandin F1alpha. Its identification forms an addendum to the paper. 9 Also present as a major product was 6(9)-oxy-11,15-dihydroxyprosta-7,13-dienoic acid.