Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.

RATIONALE: Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied. OBJECTIVES: To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP. METHODS: By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD. MEASUREMENTS AND MAIN RESULTS: Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (ß = -72.21 ml, P = 3.90 × 10(-4)) and FEV1/FVC (ß = -1.53%, P = 6.35 × 10(-6)), and with COPD (odds ratio = 1.63, P = 1.46 × 10(-5)). CONCLUSIONS: Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.

An evidence-based, multidisciplinary process for implementation of potentially better practices using a computerized medical record.

Although the Institute of Medicine of the USA has recommended elements for healthcare reform, the optimal means for incorporation of these elements into a healthcare setting remain undefined. A process for the implementation of potentially better practices is described that incorporates a computerized medical record into an evidence-based, multidisciplinary continuous quality improvement effort. Steps in the process include the following: fostering a culture change that incorporates key habits for improvement; identification of a potentially better practice; review of existing evidence and analysis of local experience; delineation of proposed outcomes and potential confounders; guideline formulation and implementation; monitoring of change effectiveness; ongoing multivariate data analyses; and policy formulation. Trainee education and family participation characterize all steps in the process. Consequently, the process incorporates all of the elements recommended by the Institute of Medicine of the USA for healthcare reform and may be adapted to any healthcare setting.

Infant temperament and maternal anxiety and depressed mood in the early postpartum period.

Although difficult infant temperament has been associated with maternal postpartum anxiety and depressed mood in later infancy, the emergence of this association in the early postpartum period has not been explored. In a survey study of 296 mothers of healthy term newborns during the first postpartum month, the relationship of infant temperament with maternal anxiety and depressed mood was explored. Maternal ratings of infant temperament were measured by the Early Infancy Temperament Questionnaire. Postpartum anxiety was measured by the State Scale of the State-Trait Anxiety Inventory and depressed mood by the Beck Depression Inventory. The State Scale and Beck Depression Inventory correlated positively with ratings of infant activity, rhythmicity, approach, distractibility, and overall temperamental difficulty. In addition, the State Scale correlated positively with ratings of adaptability and intensity. In regression analyses, controlling for other factors, ratings of overall temperamental difficulty were independently associated with both State Scale and Beck Depression Inventory scores. Associations of difficult infant temperament with maternal postpartum anxiety and depressive symptoms emerge early in the postpartum period. These associations are independent of other known contributors to postpartum mood.

The threshold force required for femoral impaction grafting in revision hip surgery.

BACKGROUND AND PURPOSE: Femoral impaction grafting requires vigorous impaction to obtain adequate stability without risk of fracture, but the force of impaction has not been determined. We determined this threshold force in a preliminary study using animal femurs. METHODS: Adult sow femurs were used because of their morphological similarity to human femurs in revision hip arthroplasty. 35 sow femurs were impacted with morselized bone chips and an increasing force was applied until the femur fractured. This allowed a threshold force to be established. 5 other femurs were impacted to this force and an Exeter stem was cemented into the neomedullary canal. A 28-mm Exeter head was attached and loaded by direct contact with a hydraulic testing machine. Axial cyclic loading was performed and the position sensor of the hydraulic testing machine measured the prosthetic head subsidence. RESULTS: 29 tests were completed successfully. The threshold force was found to be 4 kN. There was no statistically significant correlation between the load at fracture and the cortex-to-canal ratio or the bone mineral density. Following impaction with a maximum force of 4 kN, the average axial subsidence was 0.28 mm. INTERPRETATION: We achieved a stable construct without fracture. Further studies using human cadaveric femurs should be done to determine the threshold force required for femoral impaction grafting in revision hip surgery.

Use of self-controlled analytical techniques to assess the association between use of prescription medications and the risk of motor vehicle crashes.

Case-crossover and case-series analyses are 2 epidemiologic approaches that can be used to evaluate the association of exposures with acute events. Using a primary care database from the United Kingdom and these 2 statistical approaches, the authors investigated the impact of using benzodiazepines, nonbenzodiazepine hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor vehicle crash was documented. The outcome of the case-crossover analyses varied according to the choice of control period, so the case-series approach was preferred. The first 4 weeks of treatment with a combined acetaminophen and opioid preparation was associated with an increased risk of motor vehicle crash (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39, 2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval: 1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine hypnotics, and antihistamines for more than 4 weeks was associated with motor vehicle crash, but shorter term use was not. The results obtained are broadly consistent with those from well-designed case-control studies and demonstrate how case-only techniques optimize the use of routinely collected data for epidemiologic studies.

An evaluation of the use of bronchoconstriction induced by deep inspiration as a new epidemiological measure for asthma.

RATIONALE: Bronchoconstriction after deep inhalation is associated with increased severity of asthma and is also a predictor of length of hospital stay in individuals admitted with asthma exacerbations. We hypothesized that this effect may represent a new non-invasive method to assess bronchial reactivity and other measures of asthma control. METHODS: We used a cross-sectional study design recruiting participants 18 to 65 years of age with a physician diagnosis of asthma. All participants were asked to provide three serial peak expiratory flow rate (PEFR) measurements in the morning, and bronchial reactivity was measured up to a maximum inhaled dose of 24.5 micromoL methacholine on the same day. Participants also recorded their asthma symptoms score and bronchodilator use during the 7 days before measuring bronchial reactivity. RESULTS: A total of 127 people provided data for analysis. There was no significant relationship between bronchoconstriction after deep inhalation (as measured by three serial PEFR measurements) and either bronchial reactivity to methacholine, asthma symptoms, or bronchodilator use. CONCLUSIONS: Bronchoconstriction induced by deep inspiration does not appear to be a valid marker of airway hyperresponsiveness or asthma severity in adults with mild to moderate asthma.

Exhaled carbon monoxide in asthmatic adults with bronchial reactivity: a prospective study.

HYPOTHESIS: We hypothesized that eCO may permit non-invasive assessment of disease activity in adults with asthma and bronchial reactivity. METHODS: A total of 209 participants 18 to 65 years of age with a diagnosis of asthma and bronchial reactivity provided data for analysis. The association between eCO and bronchial reactivity, forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), peak expiratory flow rate measurements (PEFR), asthma symptoms score, and bronchodilator use cross-sectionally and within-subject change in eCO were analyzed in relation to change in these variables over 6 weeks. RESULTS: There was no difference in eCO in those who were taking inhaled corticosteroids and those who were not (p = 0.33). There was also no cross-sectional or within-in subject association between eCO and bronchial reactivity, FEV(1), FVC, PEFR, symptoms score, or bronchodilator use. CONCLUSIONS: In a population of adults with bronchial reactivity, eCO has no or very limited potential as a biomarker of asthma activity.

Does a low sodium diet improve asthma control? A randomized controlled trial.

RATIONALE: Observational studies and initial randomized trials have indicated that a low sodium diet may improve asthma control. OBJECTIVES: We tested the hypothesis that a low sodium diet would improve asthma control over a 6-week period. METHODS: Participants with a physician diagnosis of asthma and measurable bronchial reactivity to methacholine entered a randomized double-blind placebo-controlled trial. All adopted a low sodium diet and were randomized to receive either 80 mmol/day of oral sodium supplements (normal sodium intake) or matched placebo (low sodium intake) for 6 weeks. The primary outcome was change in bronchial reactivity to methacholine; secondary outcomes were change in lung function, morning and evening peak expiratory flow, asthma symptoms score, daily bronchodilator use, Juniper Standardized Asthma Quality of Life Questionnaire score, and atopy. MEASUREMENTS AND MAIN RESULTS: A total of 220 individuals entered the study, of whom 199 completed the protocol. In the low sodium-intake group, mean daily urinary sodium excretion decreased by 20 mmol (SD, 64 mmol) and in the normal-sodium-intake group increased by 28 mmol (SD, 74 mmol). There were no differences between the two groups in the primary or secondary outcome measures; the mean difference in bronchial reactivity between the low- and normal-intake groups was -0.03 doubling doses of methacholine (95% confidence interval, -0.60 to 0.53). CONCLUSIONS: The use of a low sodium diet as an adjunctive therapy to normal treatment has no additional therapeutic benefit in adults with asthma and bronchial reactivity to methacholine.

A prospective study of weight change and systemic inflammation over 9 y.

BACKGROUND: An increase in weight is a risk factor for cardiovascular disease and cancer. This increased risk may be mediated by inflammation, but no long-term data are available on the effect of weight gain on systemic inflammation. OBJECTIVE: We tested the hypothesis that weight gain is associated with an increase in systemic inflammation during a 9-y period. DESIGN: In 1991 data on body weight and a blood sample were collected from a random sample of 2425 randomly selected adults from a community-based cohort in Nottingham, United Kingdom. In 2000, these measures were repeated in 1301 of these participants. The main outcome measure was change in systemic inflammation as measured by serum C-reactive protein (CRP) from the 1222 participants who provided paired samples. RESULTS: The mean change in weight from 1991 to 2000 was 2.9 kg (95% CI: 2.6, 3.2 kg). The geometric mean of CRP in 1991 was 1.22 mg/L (95% CI: 0.03, 125.0 mg/L), and it increased to 1.76 mg/L (95% CI: 0.09, 62.0 mg/L) in 2000 (P<0.001). A linear association was observed between increase in weight and serum CRP, with a 1-kg increment in weight being associated with an additional increase in CRP of 0.09 mg/L (95% CI: 0.02, 0.16 mg/L) during this time period. CONCLUSION: During a 9-y period, an increase in weight is associated with an increase in systemic inflammation. This provides a mechanism that may explain some of the previously reported association of weight gain with an increased risk of both cancer and cardiovascular disease.

Maternal anxiety: course and antecedents during the early postpartum period.

The early course and antecedents of postpartum anxiety are unknown. This study sought to determine the course and antecedents of maternal anxiety during the first month postpartum and to develop a model to predict 1-month anxiety using information obtainable before perinatal hospital discharge. Two hundred and ninety-six mothers were screened before discharge with the State (SS) and Trait (TS) Scales of the State Trait Anxiety Inventory (STAI). Demographic characteristics were assessed by questionnaire and medical record review, and psychiatric history, measures of perinatal stress, and resilient factors were determined by focused questions and formal instruments. At 1-month postpartum, the SS was repeated. Scores on the SS were significantly higher at 1 month than immediately postpartum (35.30+/-0.68 versus 33.38+/-0.60, mean+/-standard error, P=.004), but only 58.6% of mothers with high pre-discharge anxiety had high anxiety at 1 month. One-month anxiety correlated with pre-discharge SS and TS scores, a history of psychiatric problems including depressed mood, medical and negative social life events, lack of pregnancy planning and prenatal class attendance, perceived peripartum stress, and duration of postpartum hospital stay. Inverse correlations were observed with education, household income, and resiliency factors. In multivariate modeling, anxiety trait, education, history >or=2 years of depression, and perception of peripartum stress accounted for 50% of the variance in the 1-month SS score. Maternal anxiety increases during the first postpartum month. Women with high trait anxiety, low education, a history of depressed mood, and a perception of high peripartum stress are at risk for experiencing anxiety at this time.

Maternal self-concept and breastfeeding.

To test the hypothesis that mothers with high self-concept will be more likely to breastfeed their infants than those with lower self-concept, 2 cohorts of mothers of term newborns were assessed by different forms of the Tennessee Self-Concept Scale. In study 1, mothers exclusively breastfeeding at 1 month postpartum had significantly higher self-concept than those exclusively formula feeding. In study 2, exclusively breastfeeding mothers had higher scores for total self-concept compared with those exclusively formula feeding. Exclusively breastfeeding mothers also scored higher on several individual dimensions of self-concept, notably those reflecting self-satisfaction, behavior, moral worth, value as a family member, and physical appearance. Mothers partially breastfeeding had intermediate levels of self-concept in both studies. Even after controlling for demographic and social factors and for breastfeeding initiation in regression analyses, self-concept remained significantly associated with exclusive breastfeeding in both studies. Thus, compared with mothers who exclusively formula feed their infants, exclusively breastfeeding mothers have higher levels of self concept.

Predicting revision risk for aseptic loosening of femoral components in total hip arthroplasty in individual patients--a finite element study.

Advances in surgical procedure, prosthesis design, and biomaterials performance have considerably increased the longevity of total joint replacements. Preoperative planning is another step in joint replacement that may have the potential to improve clinical outcome for the individual patient, but has remained relatively consistent for a long time. One means of advancing this aspect of joint replacement surgery may be to include predictive computer simulation into the planning process. In this article, the potential of patient-specific finite element analysis in preoperative assessment is investigated. Seventeen patient-specific finite element models of cemented Charnley reconstructions were created, of which six were early (<10 years) revisions. Creep was simulated using a Maxwell model, and fatigue damage was simulated using an anisotropic continuum damage formulation. Account was taken of the relationship between annual loading cycles and age, and stair-climbing loads were included using a walking to stair-climbing cycle ratio of 9:1. Simulations for the equivalent of 10 years of loading were performed. Accumulated damage, inducible displacement, and migration were computed. Five of the six early revisions had the highest migration indicating that migration could have been used to identify early failures of these prostheses. Resultant migration showed the most significant difference between the early revised and unrevised groups (p = 0.0024). Furthermore, this trend was apparent from 1 year postimplantation (p = 0.0052). This ability to differentiate early revisions shows that computational simulation of aseptic loosening in cemented prostheses could prove clinically useful in helping surgeons optimize the preoperative plan for individual patients.

Hospital construction and postpartum anxiety.

OBJECTIVE: To explore the hypothesis that environmental stress in the form of construction on a postpartum ward may be associated with enhanced maternal anxiety. METHODS: Four hundred twenty-two mothers delivering at a university hospital were screened prior to discharge for anxiety using the State Scale of the State Trait Anxiety Inventory (STAI). Recent medical life events, perceived stress, mastery, marital satisfaction and discharge readiness were assessed by questionnaire and medical record review. During the latter part of the study, 9.5% of the women were subjected to construction on the postpartum ward. RESULTS: STAI scores were significantly higher among women hospitalized during construction compared to those hospitalized prior to construction (37.03+/-1.83 vs. 33.34+/-0.51, P=.030). In a multivariate analysis controlling for other covariates associated with anxiety, construction remained a significant independent predictor of the STAI score. CONCLUSIONS: Construction on a postpartum ward may be associated with increased maternal anxiety. This finding suggests that maternal anxiety at this sensitive time may be influenced by environmental factors.

Postpartum anxiety and breast feeding.

OBJECTIVE: To evaluate the relationship between postpartum anxiety and lactation experience, knowledge, confidence and performance. STUDY DESIGN: State anxiety was measured among breast-feeding women by the State Trait Anxiety Inventory before hospital discharge and at 1 month postpartum. Breast-feeding experience and knowledge were assessed by focused questions and confidence by the Breastfeeding Confidence Scale. Breast-feeding performance measures included breast-feeding immediately after delivery; formula supplementation in the hospital; full, exclusive breast-feeding; and breast-feeding termination at 1 month postpartum. RESULTS: Predischarge anxiety correlated inversely with breast-feeding confidence (r [339] = -0.27, p = 0.000) but not with experience or knowledge. As compared to low-anxiety mothers, those with high anxiety were less likely to breast-feed after delivery (53.0% vs. 65.1%, p = 0.049) and more likely to give their infants formula (43.9% vs. 29.1%, p = 0.022). In logistic regression models adjusting for demographic and social factors, high-anxiety mothers were less likely to practice full, exclusive breast-feeding (AOR = 0.39; 95% CI 0.20, 0.74; p < 0.005) and more likely to have terminated breastfeeding at 1 month (AOR = 4.40; 95% CI 1.70, 11.33; p < 0.005). CONCLUSION: Postpartum anxiety may be associated with reduced breast-feeding confidence and lactation performance. Awareness of this association may be helpful in identifying women at risk for lactation failure and targeting efforts to promote breast-feeding.

Reduced Necrotizing Enterocolitis after an Initiative to Promote Breastfeeding and Early Human Milk Administration.

INTRODUCTION: We sought to reduce the incidence of necrotizing enterocolitis (NEC) in premature infants (PI) by fostering the postnatal establishment of protective intestinal bacteria through early administration of human milk (HM) and probiotics. METHODS: A multidisciplinary team implemented an initiative to support breastfeeding (BF) and provide early postnatal supplemental donor human milk (DHM) and probiotics to PI. Interventions included process improvements in milk preparation, storage, and fortification. PI admitted to our NICU between 2006 and 2015 were monitored for feeding of HM, DHM, and preterm formula (PF), frequency of early feedings, and incidence of NEC. RESULTS: Retrospective review of 2557 cases revealed post-initiative increases in the percentage of PI receiving HM (91.5% to 96.1%), HM within 48 hours of birth (75% to 90.6%), and DHM (17.7% to 71.9%). The percentage of infants receiving feedings on day one increased from 23.9% to 44.6% while the percentage receiving PF within the first 72 hours declined (31.2% to 10.3%). The NEC rate declined from 4.1% to 0.4%. Reduction in NEC occurred despite a simultaneous increase in perinatal antibiotic exposure and the universal but late administration of bovine HM fortifier. The improvement associated with the decrease in NEC included initiation of probiotic administration, a reduction in PF feeding, and improvements in milk preparation, storage, and fortification processes. CONCLUSIONS: Early exclusive feedings of HM and avoidance of PF together with probiotics and milkhygiene may decrease NEC in PI. Neither brief perinatal antibiotic exposure nor late introduction of bovine fortifiers appears detrimental in this context.

Global satisfaction with perinatal hospital care: stability and relationship to anxiety, depression, and stressful medical events.

To evaluate the stability of global maternal satisfaction with perinatal hospital care during the post-partum period and its relationship to anxiety, depression, and stressful medical events, a cohort study of 300 mothers delivering at a university hospital was performed during the first month postpartum. Satisfaction, measured on a 4-point Likert scale (0-3), declined from 2.75 +/- 0.03 (mean +/- standard error) before hospital discharge to 2.48 +/- 0.04 at 1 month postpartum (P = .000), and only 69.5% of mothers very much satisfied predischarge remained so at 1 month (P = .000). Predischarge satisfaction declined with greater medical events (adjusted odds ratio [AOR] = 0.85, 95% confidence interval [CI] = 0.74, 0.97, P < .05) and with concomitant anxiety (AOR= 0.92, CI= 0.89, 0.95, P< .001); reduced satisfaction at 1 month was associated with high anxiety (AOR = 0.97, CI = 0.95, 0.98) and depression (AOR = 0.96, CI = 0.93, 0.99) at that time. Thus, perinatal satisfaction may be time-dependent and associated with contemporaneous medical and psychological changes.

Healthcare Reimbursement and Quality Improvement: Integration Using the Electronic Medical Record Comment on "Fee-for-Service Payment--an Evil Practice That Must Be Stamped Out?".

Reimbursement for healthcare has utilized a variety of payment mechanisms with varying degrees of effectiveness. Whether these mechanisms are used singly or in combination, it is imperative that the resulting systems remunerate on the basis of the quantity, complexity, and quality of care provided. Expanding the role of the electronic medical record (EMR) to monitor provider practice, patient responsiveness, and functioning of the healthcare organization has the potential to not only enhance the accuracy and efficiency of reimbursement mechanisms but also to improve the quality of medical care.

Pay for performance for salaried health care providers: methodology, challenges, and pitfalls.

Pay for performance has been recommended by the Institute of Medicine as an incentive to improve the quality of health care. Traditional quality-improvement methods may be adapted to evaluate performance of salaried providers, but it is important to separate provider contributions from other influencing factors within the health care system. Accurate recording, extraction, and analysis of data together with careful selection and measurement of indicators of performance are crucial for meaningful assessment. If appropriate methodology is not used, much time, effort, and money may be expended gathering data that may be potentially misleading or even useless, with the possibility that good performance may go unrecognized and mediocre performance rewarded.

The assessment of satisfaction with care in the perinatal period.

Patient satisfaction is frequently used to evaluate the quality of medical care and to guide the development of health care services. Improved satisfaction is a goal recommended by the Institute of Medicine and the government of the United Kingdom for health care reform. During the perinatal period, dynamic changes in physical and psychological state impose unique challenges in the assessment of satisfaction. This article reviews the measurement of satisfaction with care, together with factors that may influence satisfaction and its measurement during the perinatal period. Recommendations are also provided for further research and development of satisfaction instruments and potential interventions to improve satisfaction with perinatal care.

Prenatal and passive smoke exposure and incidence of asthma and wheeze: systematic review and meta-analysis.

OBJECTIVES: Exposure to passive smoke is a common and avoidable risk factor for wheeze and asthma in children. Substantial growth in the prospective cohort study evidence base provides an opportunity to generate new and more detailed estimates of the magnitude of the effect. A systematic review and meta-analysis was conducted to provide estimates of the prospective effect of smoking by parents or household members on the risk of wheeze and asthma at different stages of childhood. METHODS: We systematically searched Medline, Embase, and conference abstracts to identify cohort studies of the incidence of asthma or wheeze in relation to exposure to prenatal or postnatal maternal, paternal, or household smoking in subjects aged up to 18 years old. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by using random effects model. RESULTS: We identified 79 prospective studies. Exposure to pre- or postnatal passive smoke exposure was associated with a 30% to 70% increased risk of incident wheezing (strongest effect from postnatal maternal smoking on wheeze in children aged ≤2 years, OR = 1.70, 95% CI = 1.24-2.35, 4 studies) and a 21% to 85% increase in incident asthma (strongest effect from prenatal maternal smoking on asthma in children aged ≤2 years, OR = 1.85, 95% CI = 1.35-2.53, 5 studies). CONCLUSIONS: Building upon previous findings, exposure to passive smoking increases the incidence of wheeze and asthma in children and young people by at least 20%. Preventing parental smoking is crucially important to the prevention of asthma.