Norma Terrin

Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials.

Funnel plots, and tests for funnel plot asymmetry, have been widely used to examine bias in the results of meta-analyses. Funnel plot asymmetry should not be equated with publication bias, because it has a number of other possible causes. This article describes how to interpret funnel plot asymmetry, recommends appropriate tests, and explains the implications for choice of meta-analysis model

The case of the misleading funnel plot

Evidence based medicine insists on rigorous standards to appraise clinical interventions. Failure to apply the same rules to its own tools could be equally damaging

Favorable Impact of a Multidisciplinary Antibiotic Management Program Conducted During 7 Years

OBJECTIVE To evaluate the impact of an interventional multidisciplinary antibiotic management program on expenditures for antibiotics and on the incidence of nosocomial infections caused by Clostridium difficile and antibiotic-resistant pathogens during 7 years. DESIGN Prospective study with comparison with preintervention trends. SETTING University-affiliated teaching hospital. PATIENTS All adult inpatients. INTERVENTION A multidisciplinary antibiotic management program to minimize the inappropriate use of third-generation cephalosporins was implemented in 1991. Its impact was evaluated prospectively. The incidence of nosocomial C. difficile and resistant Enterobacteriaceae infections as well as the rate of vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of National Nosocomial Infections Surveillance System hospitals of similar size. RESULTS Following implementation of the program, there was a 22% decrease in the use of parenteral broad-spectrum antibiotics (P < .0001) despite a 15% increase in acuity of patient care during the following 7 years. Concomitantly, there was a significant (P = .002) decrease in nosocomial infections caused by C. difficile and a significant (P = .02) decrease in nosocomial infections caused by resistant Enterobacteriaceae. The program also appeared to have a favorable impact on VRE rates without a sustained impact on MRSA rates. CONCLUSION These results suggest that an ongoing multidisciplinary antibiotic management program may have a sustained beneficial impact on both expenditures for antibiotics and the incidence of nosocomial infection by C. difficile and resistant bacterial pathogens.

Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis.

BACKGROUND The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis

Objectives To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection). Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews. Study selection Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group. Data extraction Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators. Results Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53). Conclusions Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study.

Meta-analysis of diagnostic tests for acute sinusitis

To facilitate management of acute sinusitis, we conducted a meta-analysis of published studies comparing diagnostic tests for this disorder. Thirteen studies were identified through literature search. Based on sinus puncture/aspiration (considered most accurate), 49-83% of symptomatic patients had acute sinusitis. Compared with puncture/aspiration, radiography offered moderate ability to diagnose sinusitis (summary receiver operator curve [SROC] area, 0.83). Using sinus opacity or fluid as the criterion for sinusitis, radiography had sensitivity of 0.73 and specificity of 0.80. Studies evaluating ultrasonography revealed substantial variation in test performance. The clinical evaluation, particularly risk scores formally incorporating history and physical examination findings, had moderate ability to identify patients with positive radiographs (SROC area, 0.74). Many studies were of poor quality, with inadequately described test methods and unblinded test interpretation. In conclusion, acute sinusitis is common among symptomatic patients. Radiography and clinical evaluation (especially risk scores) appear to provide useful information for diagnosis of sinusitis.

External validity of predictive models: a comparison of logistic regression, classification trees, and neural networks

BACKGROUND AND OBJECTIVE The utility of predictive models depends on their external validity, that is, their ability to maintain accuracy when applied to patients and settings different from those on which the models were developed. We report a simulation study that compared the external validity of standard logistic regression (LR1), logistic regression with piecewise-linear and quadratic terms (LR2), classification trees, and neural networks (NNETs). METHODS We developed predictive models on data simulated from a specified population and on data from perturbed forms of the population not representative of the original distribution. All models were tested on new data generated from the population. RESULTS The performance of LR2 was superior to that of the other model types when the models were developed on data sampled from the population (mean receiver operating characteristic [ROC] areas 0.769, 0.741, 0.724, and 0.682, for LR2, LR1, NNETs, and trees, respectively) and when they were developed on nonrepresentative data (mean ROC areas 0.734, 0.713, 0.703, and 0.667). However, when the models developed using nonrepresentative data were compared with models developed from data sampled from the population, LR2 had the greatest loss in performance. CONCLUSION Our results highlight the necessity of external validation to test the transportability of predictive models.

Asymmetric Dimethylarginine and Mortality in Stages 3 to 4 Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, reduces bioavailability of nitric oxide and induces endothelial dysfunction. This dimethylated amino acid accumulates in chronic kidney disease and may be involved in the pathophysiology of cardiovascular disease (CVD) in this population. DESIGN, SETTINGS, PARTICIPANTS, & METHODS The Modification of Diet in Renal Disease Study was a randomized, controlled trial conducted between 1989 and 1993. We measured ADMA in frozen samples collected at baseline (n = 820) and obtained survival status, up to December 31, 2000, from the National Death Index. We examined the relationship of ADMA with prevalent CVD and performed multivariable Cox models to examine the relationship of ADMA with all-cause and CVD mortality. RESULTS Mean (SD) age was 52 (12) yr, GFR was 32 +/- 12 ml/min per 1.73 m(2), and ADMA was 0.70 +/- 0.25 micromol/L. A 1-SD increase in ADMA was associated with a 31% increased odds of prevalent CVD in an adjusted logistic regression model. During the 10-yr follow-up period, 202 (25%) participants died of any cause, 122 (15%) from CVD, and 545 (66%) reached kidney failure. In multivariable Cox models, a 1-SD increase in ADMA was associated with a 9% increased risk for all-cause and 19% increased risk for CVD mortality. CONCLUSIONS In this cohort of patients with predominantly nondiabetic, stages 3 to 4 chronic kidney disease, there was a strong association of ADMA with prevalent CVD and a modest association with all-cause and CVD mortality.

Health Behaviors in Cancer Survivors

PURPOSE/OBJECTIVES To describe health behaviors of cancer survivors by cancer diagnosis and to compare them to people without a personal or family cancer history. DESIGN Cross-sectional secondary data analysis. SETTING A national, list-assisted telephone survey using random-digit dialing of U.S. adults about use of cancer-related information and cancer beliefs. SAMPLE 619 cancer survivors and 2,141 participants without a history of cancer from the original 6,369 Health Information National Trends Survey (HINTS) respondents. METHODS Using the National Cancer Institutes 2003 HINTS, further analyses were conducted. MAIN RESEARCH VARIABLES Cancer history, current smoking, fruit and vegetable consumption, physical activity, and body mass index (BMI). FINDINGS When controlling for demographic variables, no differences were found in self-reported health behaviors between survivors and those without cancer: 22.5% of survivors and 18.4% of those without cancer were current smokers, 18% of survivors and 14.9% of those without cancer consumed at least five fruits or vegetables per day, 45.3% of survivors and 53% of those without cancer were physically active at least weekly, and 58% of survivors and 54.9% of those without cancer were overweight or obese (i.e., BMI > 25). Only 7.4% of survivors and 6.4% of participants without cancer reported positively on all three health behaviors and had a healthy or normal weight. CONCLUSIONS Survivors did not have different health behaviors when compared to participants without a history of cancer. Neither group met the American Cancer Society or Healthy People 2010 objectives for these behaviors. Adoption of healthy lifestyle behaviors should be addressed in cancer survivors. IMPLICATIONS FOR NURSING Cancer survivors need to be assessed for current smoking, dietary habits, physical activity, and weight. Information and resources should be made available, if needed, to promote the adoption of healthy lifestyle behaviors.

Neurodevelopmental outcomes of congenital diaphragmatic hernia survivors followed in a multidisciplinary clinic at ages 1 and 3

PURPOSE Infants who survive congenital diaphragmatic hernia (CDH) repair may have ongoing medical and neurodevelopmental morbidity after hospital discharge. We evaluated the relationship between medical and neurodevelopmental outcomes of CDH survivors seen in a multidisciplinary clinic at ages 1 and/or 3. METHODS From January 1997 to December 2004, 69 (61%) of 112 CDH survivors were followed in our CDH clinic at ages 1 and/or 3. Medical issues (cardiac, pulmonary, gastrointestinal) were tabulated at hospital discharge and at follow-up. Neurodevelopmental data were obtained from clinic assessments by a neurodevelopmental pediatrician. Descriptive results were summarized for each cohort. Multivariate analyses were performed to identify predictors of motor problems at age 1. RESULTS Of the 69 study participants, 64% were male, 75% had left-sided CDH, 17% had cardiac anomalies, and 25% had other congenital malformations. Nearly all required ventilator management (99%) with a median ventilator time of 14 days (range, 1-54 days); 30% required extracorporeal membrane oxygenation. While 87% of patients had medical issues at hospital discharge, 61% and 67% had medical issues at ages 1 and 3, respectively. Pulmonary problems were noted in 34% and 33% of the ages 1 and 3 cohorts, respectively. Motor and language problems were detected in 60% and 18% of the age 1 cohort and 73% and 60% of the age 3 cohort, respectively. Multivariate analysis found ventilator time as the only independent predictor of motor problems at age 1 (odds ratio, 1.12 per day; 95% confidence interval, 1.05-1.20; P < .01). CONCLUSIONS Young CDH survivors continue to have ongoing medical problems and a high incidence of motor and language problems. Duration of neonatal ventilatory support was a significant predictor of motor problems at age 1. Prospective studies are needed to confirm these findings.