Clinical research training and capacity building for prevention and control of non-communicable diseases: A programme in India.

BACKGROUND.: Non-communicable diseases (NCDs)-a term which includes diabetes, cardiovascular disease, cancers, chronic respiratory diseases, and mental illness-are now the major cause of death in India and pose healthcare and economic challenges. There is an urgent need for enhanced clinical research training and capacity building for NCD prevention and control in India. METHODS.: We describe a multi-pronged approach funded in part by the US National Institutes of Health Fogarty International Center, which was initiated in 2001, to train Indian present and future scientists/doctors in NCD prevention and control. The approaches used were annual national seminars, intensive training courses, in-house workshops, short-term training sessions in the USA and monthly video conferences. RESULTS.: During 2001-2016, a total of 3650 undergraduate, postgraduate and faculty from medical colleges and institutes from almost all states in India and several neighbouring countries participated in seminars and other capacity-building workshops held at the Madras Diabetes Research Foundation, Chennai and at six other medical colleges; 883 delegates participated in the in-house workshops, 463 in the intensive interactive sessions; 244 in workshops on advanced techniques in genomics; and 37 in short-term training sessions held in the USA. CONCLUSION.: Through this unique capacity-building programme, more than 5000 individuals representing faculty and students from various medical colleges and research institutes across, and beyond, India, underwent training in the prevention and control of NCDs.

Assessing the Congregate Disaster Shelter: Using Shelter Facility Assessment Data for Evaluating Potential Hazards to Occupants During Disasters.

Disaster shelter assessments are environmental health assessments conducted during disaster situations to evaluate the living environment of shelters for hygiene, sanitation, and safety conditions. We conducted a secondary data analysis of shelter assessment records available (n = 108) on ice storms, floods, and tornado events from 1 state jurisdiction. Descriptive statistics were used to analyze results of environmental health deficiencies found in the facilities. The greater numbers of environmental health deficiencies were associated with sanitation (26%), facility physical issues (19%), and food areas (17%). Most deficiencies were reported following ice storms, tornadoes, and flood events. This report describes the first analysis of environmental health deficiencies found in disaster shelters across a spectrum of disaster events. Although the number of records analyzed for this project was small and results may not be generalizable, this new insight into the living environment in shelter facilities offers the first analysis of deficiencies of the shelter operation and living environment that have great potential to affect the safety and health of shelter occupants.

Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the Coronary Artery Risk Development in Young Adults Women's study.

OBJECTIVE: To study the independent associations of polycystic ovary syndrome (PCOS), and its 2 components, hyperandrogenism and anovulation, with coronary artery calcification (CAC) and carotid artery intima-media thickness (IMT). APPROACH AND RESULTS: At the year 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort of young adults, women (mean age, 45 years) with information on menses and hirsutism in their twenties were assessed for CAC (n=982) and IMT (n=988). We defined PCOS as women who had both irregular menses and hyperandrogenism (n=55); isolated oligomenorrhea (n=103) as women who only had irregular menses; and isolated hyperandrogenism (n=156) as women who had either hirsutism or increased testosterone levels. Logistic regressions and general linear models were used to estimate the associations between components of PCOS and subclinical CVD. The prevalence of CAC was 10.3% overall. Women with PCOS had a multivariable adjusted odds ratio of 2.70 (95% confidence interval, 1.31-5.60) for CAC. Women with either isolated oligomenorrhea or isolated hyperandrogenism had no increased risk of CAC when compared with unexposed women. Women with PCOS had significantly increased bulb and internal carotid-IMT measurements; however, no significant differences were noted in bulb or internal carotid artery IMT among women with either isolated oligomenorrhea or isolated hyperandrogenism when compared with unexposed women. There were no differences in common carotid-IMT among the 4 study groups. CONCLUSIONS: In this study, women with PCOS, manifested as both anovulation and hyperandrogenism, but not women with one of these manifestations alone, were at increased risk for the development of subclinical CVD.

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

The Decision to Repair or Replace a Defective Restoration is Affected by Who Placed the Original Restoration: Findings from the National Dental PBRN.

OBJECTIVES: To evaluate how restoration characteristics are associated with the decision to repair or replace an existing restoration. The following hypotheses were studied: dentists who placed the original restoration are more likely to repair instead of replace restorations (H1) that are in molar teeth; (H2) that are in the upper arch; (H3) that have amalgam restorative material; (H4) if a fracture is not the primary reason for the defect; and (H5) when the restoration comprises more than one surface. METHODS: This cross-sectional study used a consecutive patient/restoration recruitment design. 194 dentists members of a dental practice-based research network recorded data on restorations in permanent teeth that needed repair or replacement. RESULTS: For 6,623 of the 8,770 defective restorations in 6,643 patients, the treatment was provided by the dentist who had not placed the original restoration (75%). The 2-way interaction revealed that dentists who had placed the original restoration often chose to repair when the defective restoration was in a molar, relative to premolar or anterior teeth (OR = 2.2, p <.001); and chose to replace when the restoration had amalgam (OR = 0.5, p < .001), and when it was a fracture compared to another reason (OR = 0.8, p = 001). CONCLUSION: Most dentists are not conservative when they revisit a restoration that they originally placed regardless of type of failure, number of surfaces or material used. However, dentists who had placed the original restoration were significantly more likely to repair it when the defective restoration was in a molar tooth. CLINICAL SIGNIFICANCE: Most dentists who placed the original restoration were prone to replace it, however if the defective restoration was located in a molar tooth they would consider repairing it.

Androgenicity in Young Women and Development of Metabolic Syndrome Before Menopause: The CARDIA and CARDIA Women's Studies.

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause. Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up. Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used. Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users. Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Racial differences in incident heart failure among young adults.

BACKGROUND: The antecedents and epidemiology of heart failure in young adults are poorly understood. METHODS: We prospectively assessed the incidence of heart failure over a 20-year period among 5115 blacks and whites of both sexes who were 18 to 30 years of age at baseline. Using Cox models, we examined predictors of hospitalization or death from heart failure. RESULTS: Over the course of 20 years, heart failure developed in 27 participants (mean [+/-SD] age at onset, 39+/-6 years), all but 1 of whom were black. The cumulative incidence of heart failure before the age of 50 years was 1.1% (95% confidence interval [CI], 0.6 to 1.7) in black women, 0.9% (95% CI, 0.5 to 1.4) in black men, 0.08% (95% CI, 0.0 to 0.5) in white women, and 0% (95% CI, 0 to 0.4) in white men (P=0.001 for the comparison of black participants and white participants). Among blacks, independent predictors at 18 to 30 years of age of heart failure occurring 15 years, on average, later included higher diastolic blood pressure (hazard ratio per 10.0 mm Hg, 2.1; 95% CI, 1.4 to 3.1), higher body-mass index (the weight in kilograms divided by the square of the height in meters) (hazard ratio per 5.7 units, 1.4; 95% CI, 1.0 to 1.9), lower high-density lipoprotein cholesterol (hazard ratio per 13.3 mg per deciliter [0.34 mmol per liter], 0.6; 95% CI, 0.4 to 1.0), and kidney disease (hazard ratio, 19.8; 95% CI, 4.5 to 87.2). Three quarters of those in whom heart failure subsequently developed had hypertension by the time they were 40 years of age. Depressed systolic function, as assessed on a study echocardiogram when the participants were 23 to 35 years of age, was independently associated with the development of heart failure 10 years, on average, later (hazard ratio for abnormal systolic function, 36.9; 95% CI, 6.9 to 198.3; hazard ratio for borderline systolic function, 3.5; 95% CI, 1.2 to 10.2). Myocardial infarction, drug use, and alcohol use were not associated with the risk of heart failure. CONCLUSIONS: Incident heart failure before 50 years of age is substantially more common among blacks than among whites. Hypertension, obesity, and systolic dysfunction that are present before a person is 35 years of age are important antecedents that may be targets for the prevention of heart failure. (ClinicalTrials.gov number, NCT00005130.)

Associations between improvements in lower urinary tract symptoms and sleep disturbance over time in the CAMUS trial.

PURPOSE: We recently reported an association between the bother and severity of lower urinary tract symptoms secondary to benign prostatic hyperplasia and the severity of sleep disturbance. However, few studies have examined whether alterations in the severity of urinary symptoms influence the degree of sleep problems over time. MATERIALS AND METHODS: The severity of lower urinary tract symptoms in men enrolled in CAMUS (Complementary and Alternative Medicine for Urological Symptoms), a clinical trial of saw palmetto (Serenoa repens), was evaluated using AUASI (American Urological Association symptom index) and quality of life scores. Sleep disturbance was evaluated by the Jenkins sleep scale at 0, 24, 48 and 72 weeks. Statistical analyses were used to assess the relationship(s) between changes in lower urinary tract symptoms and sleep disturbance. RESULTS: The baseline characteristics of the 339 men (172 placebo arm and 167 saw palmetto arm) enrolled in the CAMUS trial with assessment of sleep disturbance and urinary symptoms were similar. There were no differences between improvements in the severity of sleep disturbance or urinary symptoms between the 2 experimental arms. Combined analyses of the entire cohort revealed significant associations (p <0.001) between the AUASI score and sleep disturbance severity with time. Multivariate analyses demonstrated that improvements in lower urinary tract symptoms other than nocturia were the most significant predictors of improvements in sleep disturbance. Specific analyses adjusting for other baseline characteristics demonstrated that a 3-point improvement in AUASI score was associated with a 0.73-point improvement in the Jenkins sleep scale with time. CONCLUSIONS: Improvements in lower urinary tract symptoms correlate with changes in sleeping abilities with time in men with benign prostatic hyperplasia. While nocturia is significantly associated with sleep disturbance, other changes in overall lower urinary tract symptoms are better predictors of changes in sleep dysfunction.

The relationship between lower urinary tract symptom severity and sleep disturbance in the CAMUS trial.

PURPOSE: Bothersome lower urinary tract symptoms, including nocturia, significantly impact general health related quality of life in men, as does sleep disturbance. However, few groups have examined the relationship between urinary symptom severity and sleep disturbance. MATERIALS AND METHODS: Men enrolled in a clinical trial of saw palmetto (Serenoa repens) were studied at baseline. Lower urinary tract symptom severity, as determined by the American Urological Association symptom index and quality of life scores, and the degree of sleep disturbance were determined by the Jenkins sleep scale. Analysis was done, adjusting for baseline characteristics, to identify predictors of severe sleep disturbance. RESULTS: A total of 366 men with a mean ± SD age of 60.9 ± 8.3 years who had moderate-severe lower urinary tract symptoms (mean American Urological Association symptom index score 14.58 ± 4.6 points) and a mean Jenkins sleep score of 7.3 ± 4.7 points were included in analysis. Overall there were significant associations between the American Urological Association symptom index score and sleep disturbance severity. Multivariate analysis revealed that obstructive and irritative symptoms were significantly associated with severe sleep disturbance. Further analysis showed that lower serum prostate specific antigen and post-void residual urine volume were also significantly associated with the degree of sleep disturbance. CONCLUSIONS: Lower urinary tract symptom severity is a risk factor for severe sleep disturbance in men. While nocturia was significantly associated with sleep disturbance, other lower urinary tract symptoms were also independent predictors of sleep dysfunction.

Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study.

PURPOSE: Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study. MATERIALS AND METHODS: The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986. RESULTS: By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p=0.01), even after adjusting for major atherosclerotic risk factors. CONCLUSIONS: The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology.

Relative efficiency and sample size for cluster randomized trials with variable cluster sizes.

BACKGROUND: The statistical power of cluster randomized trials depends on two sample size components, the number of clusters per group and the numbers of individuals within clusters (cluster size). Variable cluster sizes are common and this variation alone may have significant impact on study power. Previous approaches have taken this into account by either adjusting total sample size using a designated design effect or adjusting the number of clusters according to an assessment of the relative efficiency of unequal versus equal cluster sizes. PURPOSE: This article defines a relative efficiency of unequal versus equal cluster sizes using noncentrality parameters, investigates properties of this measure, and proposes an approach for adjusting the required sample size accordingly. METHODS: We focus on comparing two groups with normally distributed outcomes using t-test, and use the noncentrality parameter to define the relative efficiency of unequal versus equal cluster sizes and show that statistical power depends only on this parameter for a given number of clusters. We calculate the sample size required for an unequal cluster sizes trial to have the same power as one with equal cluster sizes. RESULTS: Relative efficiency based on the noncentrality parameter is straightforward to calculate and easy to interpret. It connects the required mean cluster size directly to the required sample size with equal cluster sizes. Consequently, our approach first determines the sample size requirements with equal cluster sizes for a pre-specified study power and then calculates the required mean cluster size while keeping the number of clusters unchanged. Our approach allows adjustment in mean cluster size alone or simultaneous adjustment in mean cluster size and number of clusters, and is a flexible alternative to and a useful complement to existing methods. Comparison indicated that we have defined a relative efficiency that is greater than the relative efficiency in the literature under some conditions. LIMITATIONS: Our measure of relative efficiency might be less than the measure in the literature under some conditions, underestimating the relative efficiency. CONCLUSIONS: The relative efficiency of unequal versus equal cluster sizes defined using the noncentrality parameter suggests a sample size approach that is a flexible alternative and a useful complement to existing methods.

Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial.

CONTEXT: Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH); however, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg/d). OBJECTIVE: To determine the effect of saw palmetto extract (Serenoa repens, from saw palmetto berries) at up to 3 times the standard dose on lower urinary tract symptoms attributed to BPH. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, multicenter, placebo-controlled randomized trial at 11 North American clinical sites conducted between June 5, 2008, and October 10, 2010, of 369 men aged 45 years or older, with a peak urinary flow rate of at least 4 mL/s, an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits, and no exclusions. INTERVENTIONS: One, 2, and then 3 doses (320 mg/d) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. MAIN OUTCOME MEASURES: Difference in AUASI score between baseline and 72 weeks. Secondary outcomes included measures of urinary bother, nocturia, peak uroflow, postvoid residual volume, prostate-specific antigen level, participants' global assessments, and indices of sexual function, continence, sleep quality, and prostatitis symptoms. RESULTS: Between baseline and 72 weeks, mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -1.36) [corrected]with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto extract and placebo groups was 0.79 points favoring placebo (upper bound of the 1-sided 95% CI most favorable to saw palmetto extract was 1.77 points, 1-sided P = .91). Saw palmetto extract was no more effective than placebo for any secondary outcome. No clearly attributable adverse effects were identified. CONCLUSION: Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00603304.

Factors associated with mortality in transplant patients with invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

Candidate molecular pathway genes related to appetite regulatory neural network, adipocyte homeostasis and obesity: results from the CARDIA Study.

Appetite regulatory neural network and adipocyte homeostasis molecular pathways are critical to long-term weight maintenance. Associations between obesity-related phenotypes and four genes in these pathways - leptin (LEP), leptin receptor (LEPR), neuropeptide Y2 receptor (NPY2R) and peptide YY (PYY) were examined in CARDIA Study participants (aged 18-30 at recruitment in 1985-6). Weight, BMI and waist circumference were measured at baseline and at years 2, 5, 7, 10, 15, and 20. Genotyping was conducted using tag SNPs characterising common genetic variations in these genes. Generalized estimating equation (GEE) models estimated associations between SNPs and repeated anthropometric measurements, controlling for sex and age. False discovery rate was used to adjust for multiple testing. In African-Americans, SNPs across the LEP gene demonstrated significant overall associations with all obesity-related phenotypes. The associations between LEP rs17151919 with weight tended to strengthen with time - the difference in weight associated with each additional minor allele increased from 2.6 kg at baseline to 4.8 kg at year 20 (SNP*time interaction p = 0.0193). NPY2R gene SNPs were associated with waist circumference among African-American men (p = 0.0462). In Caucasians, LEP SNPs also tended to be associated with weight (p = 0.0471), and PYY rs11684664 was associated with obesity-related phenotypes in women only (p = 0.010-0.026). Several LEP, and NPY2R and PYY SNPs were associated with obesity-related phenotypes in young adults, particularly among African-Americans.

Validity versus feasibility for quality of care indicators: expert panel results from the MI-Plus study.

BACKGROUND: In the choice and definition of quality of care indicators, there may be an inherent tension between feasibility, generally enhanced by simplicity, and validity, generally enhanced by accounting for clinical complexity. OBJECTIVE: To study the process of developing quality indicators using an expert panel and analyze the tension between feasibility and validity. DESIGN AND PARTICIPANTS: A multidisciplinary panel of 12 expert physicians was engaged in two rounds of modified Delphi process to refine and choose a smaller subset from 36 indicators; these were developed by a research team studying the quality of care in ambulatory post-myocardial infarction patients with co-morbidities. We studied the correlation between validity/feasibility ranks provided by the expert panel. The correlation between the quality indicators ranks on validity and feasibility scale and variance of experts' responses was also individually studied. RESULTS: Ten of 36 indicators were ranked in both the highest validity and feasibility groups. The strength of association between validity and feasibility of indicators measured by Kendall tau-b was 0.65. In terms of validity, a strong negative correlation was observed between the ranks of indicators and the variability in expert panel responses (Spearman's rho, r = -0.85). A weak correlation was found between the ranks of feasibility and the variability of expert panel responses (Spearman's rho, r = 0.23). CONCLUSION: There was an unexpectedly strong association between the validity and feasibility of quality indicators, with a high level of consensus among experts regarding both feasibility and validity for indicators rated highly on each of these attributes.

Institutional review board and regulatory solutions in the dental PBRN.

OBJECTIVES: Effectively addressing regulatory and human participant protection issues with Institutional Review Boards (IRBs, or ethics committees) and grants administration entities is an important component of conducting research in large collaborative networks. A dental practice-based research network called "DPBRN" (http://www.DPBRN.org) comprises dentists in two health maintenance organizations, several universities, seven US states, and three Scandinavian countries. Our objectives are to describe: a) the various human participants and regulatory requirements and solutions for each of DPBRN's five regions; b) their impact on study protocols and implementation; and c) lessons learned from this process. METHODS: Following numerous discussions with IRB and grants administrative personnel for each region, some practitioner-investigators are attached to their respective IRBs and contracting entities via sub-contracts between their organizations and the network's administrative site. Others are attached via Individual Investigator Agreements and contractually obligated via Memoranda of Agreement. RESULTS: IRBs approve general operations under one approval, but specific research projects via separate approvals. Various formal IRB and grants administrative agreements have been arranged to customize research to the network context. In some instances, this occurred after feedback from patients and practitioners that lengthy written consent forms impeded research and raised suspicion, instead of decreasing it. CONCLUSIONS: Instead of viewing IRBs and institutional administrators as potentially adversarial, customized solutions can be identified by engaging them in collegial discussions that identify common ground within regulatory bounds. Although time-intensive and complex, these solutions improve acceptability of practice-based research to patients, practitioners, and university researchers.

Concordance between preoperative and postoperative assessments of primary caries lesion depth: results from the Dental PBRN.

This study investigated the concordance between pre- and postoperative assessments of primary caries lesion depths by dentists from The Dental Practice-Based Research Network (DPBRN; www.DentalPBRN.org). A total of 229 DPBRN dentists collected data on 8,351 consecutive restorations inserted due to primary caries in 5,810 patients. Dentists estimated the preoperative depth of caries lesions based on the diagnostic methods they typically used. The preoperative depth was then compared to the postoperative depth, which dentists determined using actual clinical observation. Both estimated and observed depths were recorded as being in the outer half (E1) or inner half (E2) of enamel, or in the outer third (D1), middle third (D2) or inner third (D3) of dentin. Most restorations were placed to treat lesions that were preoperatively assessed as extending to the D1 (53%) and D2 (25%) depths. Of the restored caries lesions, 10% were preoperatively assessed as being limited to E2 depth and 3% to E1 depth. The majority of the restored enamel lesions were located on occlusal surfaces. Preoperative estimates of caries lesion depth were more concordant with postoperative depths when the lesion was at an advanced stage: 88% concordance at the D3 depth, compared to 54% concordance at the E1 depth. DPBRN dentists can discriminate caries lesions at different depths, but the accuracy of their depth assessments was higher for dentin than for enamel lesions. In general, DPBRN dentists were more likely to underestimate than overestimate the depth of caries lesions, and the extent of underestimation was greater for enamel than for dentin lesions.

Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation.

BACKGROUND: Circulating levels of acute phase reactant proteins such as plasma C-reactive protein (CRP) are likely influenced by multiple genes regulating the innate immune response. METHODS AND RESULTS: We screened a set of 16 inflammation-related genes for association with CRP in a large population-based study of healthy young adults (n=1627). Results were validated in 2 independent studies (n=1208 and n=4310), including a pooled analysis of all 3 studies. In the pooled analysis, the minor allele of IL1RN 1018 (rs4251961) within the gene encoding interleukin (IL)-1 receptor antagonist (IL-1RA) was significantly associated with higher mean plasma log(CRP) level (P<1 x 10(-4)). The same IL1RN 1018 allele was associated with higher mean plasma log(IL-6) levels (P=0.004). In the pooled analysis, the minor allele of IL1RN 13888 (rs2232354) was associated with higher fibrinogen, (P=0.001). The IL1RN 1018 and 13888 variant alleles tag a clade of IL1RN haplotypes linked to allele 1 of an 86-bp VNTR polymorphism. We confirmed that the IL1RN 1018 variant (rs4251961) was associated with decreased cellular IL-1RA production ex vivo. CONCLUSIONS: Common functional polymorphisms of the IL1RN gene are associated with several markers of systemic inflammation.

Pharmaceuticals companies' medication assistance programs: potentially useful but too burdensome to use?

OBJECTIVES: This study examined how physicians perceive pharmaceutical companies' medication assistance programs (MAPs). METHODS: The study was conducted using a survey of 373 primary care physicians from four southern states; they were surveyed within the formative evaluation phase of a larger study (MI-Plus). Respondents were queried about use and usefulness of MAPs for patients who cannot afford drugs, and barriers to using them. Bivariate associations between physician-level variables (patients without drug coverage) and usefulness and barriers to using MAPs were assessed using Chi square tests. Independence of associations was assessed using multiple logistic regressions. RESULTS: Of the 364 (97.6%) respondents who used MAPs, 70% used them regularly, the rest occasionally; 63% found MAPs very useful in caring for patients who could not afford drugs. About 89% reported one or more barriers to using MAPs; 47% saw "inability of patients to apply directly;" and 57% saw "enrollment process being time-consuming for staff" as barriers. Compared to physicians with fewer elderly patients without drug coverage, those with more of these patients were less likely to find MAPs very useful; less likely to report no barriers to using MAPs; and more likely to see "low income thresholds" and "inability of patients to apply directly" as barriers. CONCLUSION: While MAPs are considered useful in caring for patients in need of assistance, there are many barriers to their use. Pharmaceutical companies should address these barriers. Limitations include a low response rate (about 10%).