Derivation and validation of the UCAP-Q case-finding questionnaire to detect undiagnosed asthma and COPD.

BACKGROUND: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease. METHODS: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated. RESULTS: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD. CONCLUSIONS: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease.

Population-based case-finding to identify subjects with undiagnosed asthma or COPD.

BACKGROUND: ∼5-10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada. METHODS: Adults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD. RESULTS: 12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68). CONCLUSION: 20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease.

Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia.

BACKGROUND: The objective of this study was to examine individual and community factors that influence high-density lipoprotein cholesterol (HDL-C) dyslipidemia in Newfoundland and Labrador (NL), a genetically isolated population in Canada with a high prevalence of HDL-C dyslipidemia. METHODS: First, a group of single nucleotide polymorphisms from 10 metabolic trait candidate genes was tested using a multivariate logistic regression model. The significant SNPs were entered into the second phase, where a mixed logistic model incorporated the community disease risk factors together with the individual factors as the fixed part of the model and the geographic region as a random effect. RESULTS: Analysis of 1489 subjects (26.9% HDL-C dyslipidemia) identified rs3758539, a non-coding variant in the 5'UTR of RBP4, to be associated with HDL-C dyslipidemia (odds ratio = 1.45, 95% confidence interval = 1.08-1.97, p = 0.01). The association remained significant, and the effect size did not change after the incorporation of individual and community risk factors from 17 geographic regions (odds ratio: 1.41, 95% confidence interval = 1.03-1.93, p = 0.03) in NL. Besides this variant, sex, BMI, and smoking also showed significant associations with HDL-C dyslipidemia, whereas no role was identified for the community factors. CONCLUSIONS: This study demonstrates the use of community-level data in a genetic association testing. It reports a functional variant in the promoter of RBP4, a gene directly involved in lipoprotein metabolism, to be associated with HDL-C dyslipidemia. These findings indicate that individual factors are the main reason for a higher prevalence of HDL-C dyslipidemia in the NL population.

Six-year time-trend analysis of dyslipidemia among adults in Newfoundland and Labrador: findings from the laboratory information system between 2009 and 2014.

BACKGROUND: Dyslipidemia, an increased level of total cholesterol (TC), triglycerides (TG), low-density-lipoprotein cholesterol (LDL-C) and decreased level of high-density-lipoprotein cholesterol (HDL-C), is one of the most important risk factors for cardiovascular disease. We examined the six-year trend of dyslipidemia in Newfoundland and Labrador (NL), a Canadian province with a historically high prevalence of dyslipidemia. METHODS: A serial cross-sectional study on all of the laboratory lipid tests available from 2009 to 2014 was performed. Dyslipidemia for every lipid component was defined using the Canadian Guidelines for the Diagnosis and Treatment of Dyslipidemia. The annual dyslipidemia rates for each component of serum lipid was examined. A fixed and random effect model was applied to adjust for confounding variables (sex and age) and random effects (residual variation in dyslipidemia over the years and redundancies caused by individuals being tested multiple times during the study period). RESULTS: Between 2009 and 2014, a total of 875,208 records (mean age: 56.9 ± 14.1, 47.6% males) containing a lipid profile were identified. The prevalence of HDL-C and LDL-C dyslipidemia significantly decreased during this period (HDL-C: 35.8% in 2009 [95% CI 35.5-36.1], to 29.0% in 2014 [95% CI: 28.8-29.2], P = 0.03, and LDL-C: 35.2% in 2009 [95% CI: 34.9-35.4] to 32.1% in 2014 [95% CI: 31.9-32.3], P = 0.02). A stratification by sex, revealed no significant trend for any lipid element in females; however, in men, the previously observed trends were intensified and a new decreasing trend in dyslipidemia of TC was appeared (TC: 34.1% [95% CI 33.7-34.5] to 32.3% [95%CI: 32.0-32.6], p < 0.02, HDL-C: 33.8% (95%CI: 33.3-34.2) to 24.0% (95% CI: 23.7-24.3)], P < 0.01, LDL-C: 32.9% (95%CI:32.5-33.3) to 28.6 (95%CI: 28.3-28.9), P < 0.001). Adjustment for confounding factors and removing the residual noise by modeling the random effects did not change the significance. CONCLUSION: This study demonstrates a significant downward trend in the prevalence of LDL-C, HDL-C, and TC dyslipidemia, exclusively in men. These trends could be the result of males being the primary target for cardiovascular risk management.

Identification of Dyslipidemic Patients Attending Primary Care Clinics Using Electronic Medical Record (EMR) Data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) Database.

The objective of this study was to define the optimal algorithm to identify patients with dyslipidemia using electronic medical records (EMRs). EMRs of patients attending primary care clinics in St. John's, Newfoundland and Labrador (NL), Canada during 2009-2010, were studied to determine the best algorithm for identification of dyslipidemia. Six algorithms containing three components, dyslipidemia ICD coding, lipid lowering medication use, and abnormal laboratory lipid levels, were tested against a gold standard, defined as the existence of any of the three criteria. Linear discriminate analysis, and bootstrapping were performed following sensitivity/specificity testing and receiver's operating curve analysis. Two validating datasets, NL records of 2011-2014, and Canada-wide records of 2010-2012, were used to replicate the results. Relative to the gold standard, combining laboratory data together with lipid lowering medication consumption yielded the highest sensitivity (99.6%), NPV (98.1%), Kappa agreement (0.98), and area under the curve (AUC, 0.998). The linear discriminant analysis for this combination resulted in an error rate of 0.15 and an Eigenvalue of 1.99, and the bootstrapping led to AUC: 0.998, 95% confidence interval: 0.997-0.999, Kappa: 0.99. This algorithm in the first validating dataset yielded a sensitivity of 97%, Negative Predictive Value (NPV) = 83%, Kappa = 0.88, and AUC = 0.98. These figures for the second validating data set were 98%, 93%, 0.95, and 0.99, respectively. Combining laboratory data with lipid lowering medication consumption within the EMR is the best algorithm for detecting dyslipidemia. These results can generate standardized information systems for dyslipidemia and other chronic disease investigations using EMRs.

Low density lipoprotein cholesterol control status among Canadians at risk for cardiovascular disease: findings from the Canadian Primary Care Sentinel Surveillance Network Database.

BACKGROUND: To determine the prevalence of uncontrolled LDL-C in patients with high cardiovascular disease (CVD) risks across Canada and to examine its related factors. METHODS: Non-pregnant adults >20 years-old, who had a lipid test completed between January 1, 2009 and December 31, 2011 and were included in the Canadian Primary Care Surveillance Network (CPCSSN) database were studied. The Framingham-Risk-Score was calculated to determine the risk levels. A serum LDL-C level of >2.0 mmol/L was considered as being poorly controlled. Patients with a previous record of a cerebrovascular accident, peripheral artery disease, or an ischemic heart disease were regarded as those under secondary prevention. Logistic regression modeling was performed to examine the factors associated with the LDL-C control. RESULTS: A total of 6,405 high-risk patients were included in the study and, of this population, 68% had a suboptimal LDL-C, which was significantly associated with the female gender (OR: 3.26; 95% CI: 2.63-4.05, p < 0.0001) and no medication therapy (OR: 6.31, 95% CI: 5.21-7.65, p < 0.0001). Those with comorbidities of diabetes, hypertension, obesity, and smokers had a better LDL-C control. Rural residents (OR: 0.64, 95% CI: 0.52-0.78, p < 0.0001), and those under secondary prevention (OR: 0.42; 95 % CI: 0.35-0.51, p < 0.0001), were also more likely to have a better LDL-C control. CONCLUSION: A high proportion of high-cardiac risk patients in Canadian primary care settings have suboptimal LDL-C control. A lack of medication therapy appears to be the major contributing factor to this situation.

Disease burden in individuals with symptomatic undiagnosed asthma or COPD.

BACKGROUND: The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction. METHODS: This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria. RESULTS: 1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism. CONCLUSION: Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD.

Effects of Meteorological Factors on Hospitalizations in Adult Patients with Asthma: A Systematic Review.

Background: Environmental factors such as weather variables contribute to asthma exacerbation. The impact of meteorological factors on asthma-related hospital admissions (HAs) or emergency department visits (EDVs) has been assessed in the literature. We conducted a systematic review to establish a conclusion of whether these findings from the literature are consistent and generalizable or if they vary significantly by certain subgroups. Objective: This study aims to review the effect of meteorological variables on asthma HAs and EDVs in adults, to identify knowledge gaps and to highlight future research priorities. Method: A systematic search was conducted in electronic databases such as PubMed, Embase, and CINAHL. All studies published in English were screened and included if they met the eligibility criteria. Two independent reviewers assessed the quality of the studies and extracted the data. The available evidence was summarized and presented using a harvest plot. Results: Our initial search returned a total of 3887 articles. After screening titles, abstracts, and full texts, 16 studies were included. Thirty-one percent of the included studies (5/16) found that temperature was the only factor associated with asthma hospitalization or EDVs. Six studies (37%) found that both temperature and relative humidity were associated with HAs. Four studies (25%) identified thunderstorms as a possible factor associated with asthma hospitalization in adults. Conclusion: Our review suggests that HAs and EDVs due to asthma are associated with many meteorological factors. Among the articles included in this review, changing temperature is the most commonly studied variable. We did not find studies that measured barometric pressure, weather phenomena, or the effect of tornados. To develop effective strategies to protect subjects at risk, further studies are required.

Effects of Comorbidities on Asthma Hospitalization and Mortality Rates: A Systematic Review.

Background: Recent studies have shown that patients diagnosed with asthma who have other chronic comorbidities have severely worse medical outcomes. However, the number of available published studies in this field is lacking. The aim of this study was to determine the effects of comorbidities in asthmatic patients based on hospitalization and mortality rates. Methods: A systematic review was conducted. Data were obtained from the electronic databases PubMed, CINAHL, and Cochrane until June 15, 2018. The primary objective of this study was to determine the effects of comorbidities on asthma hospitalization and mortality. The secondary objective was to analyze the effects of asthma comorbidity with certain chronic diseases, including COPD, obesity, obstructive sleep apnea, mental illness (anxiety and depression), diabetes mellitus, hypertension, myocardial ischemia, rhinitis, and sinusitis on asthma hospitalization and mortality. Results: From potential 687 articles, only 9 were chosen based on our study inclusion criteria. Almost half of these articles were related to asthma/COPD comorbidity. There were no articles found for hypertension, myocardial ischemia, rhinitis, or sinusitis based on our inclusion/exclusion factors. Each of these 9 published articles had shown an increase in rates of hospitalization, length of stay, and/or mortality, due to asthma-related symptoms, compared to asthma-only patients. Conclusion: There was determined to be a large discrepancy between the available research for various types of comorbid conditions presenting with asthma that focus on hospitalization and mortality rates. The current available literature suggests a large impact that these comorbid diseases can have on asthma-related symptoms when present together, severely affecting a patient's quality of life. We propose that further research on the effects of these comorbidities on asthma mortality and hospitalization can yield beneficial results to improve the management of asthmatic patients.

Using Electronic Medical Record to Identify Patients With Dyslipidemia in Primary Care Settings: International Classification of Disease Code Matters From One Region to a National Database.

OBJECTIVE: To assess the validity of the International Classification of Disease (ICD) codes for identifying patients with dyslipidemia in electronic medical record (EMR) data. METHODS: The EMRs of patients receiving primary care in St. John's, Newfoundland and Labrador (NL), Canada, were retrieved from the Canadian Primary Care Sentinel Surveillance Network database. International Classification of Disease codes were first compared with laboratory lipid data as an independent criterion standard, and next with a "comprehensive criterion standard," defined as any existence of abnormal lipid test, lipid-lowering medication record, or dyslipidemia ICD codes. The ability of ICD coding alone or combined with other components was evaluated against the two criterion standards using receiver operating characteristic (ROC) analysis, sensitivity, specificity, negative predictive value (NPV) and Kappa agreement. (No specificity was reported for the comparison of ICD codes against the comprehensive criterion standard as this naturally leads to 100% specificity.). RESULTS: The ICD codes led to a poor outcome when compared with the serum lipid levels (sensitivity, 27%; specificity, 76%; PPV, 71%; NPV, 33%; Kappa, 0.02; area under the receiver operating characteristic curve (AUC), 0.51) or with the comprehensive criterion standard (sensitivity, 32%; NPV, 25%; Kappa, 0.15; AUC, 66%). International Classification of Disease codes combined with lipid-lowering medication data also resulted in low sensitivity (51.2%), NPV (32%), Kappa (0.28), and AUC (75%). The addition of laboratory lipid levels to ICD coding marginally improved the algorithm (sensitivity, 94%; NPV, 79%; Kappa, 0.85; AUC, 97%). CONCLUSIONS: The use of ICD coding, either alone or in combination with laboratory data or lipid-lowering medication records, was not an accurate indicator in identifying dyslipidemia.

Management of Malignant Pleural Effusion with ASEPT® Pleural Catheter: Quality of Life, Feasibility, and Patient Satisfaction.

Objective. The PleurX® IPC system has been used extensively in the past. Over time, management of MPE with the PleurX system can be costly. The new ASEPT pleural catheter, through advantages in design, may ultimately show cost savings. The primary outcome of this study was to evaluate safety and efficacy of the ASEPT system. Method. This single centre, prospective study enrolled 50 patients with MPE, who were followed for as long as they were alive with a catheter. Quality of Life (QoL) was assessed before, at 2 weeks, and 6 weeks after ASEPT catheter insertion using the EORTC QLQ-C30 and LC13 questionnaires. Ease of catheter use and complications were reported by physician and community nurses. Results. 50 patients with MPE with a mean age of 64.5 ± 1.9, BDI of 2.8 ± 0.9, and ECOG score of 3.0 ± 0.7 were recruited. No immediate or long-term complications were reported during the study period. Compared to precatheter insertion, global health status (-18, p < 0.001), QLQ-C30 dyspnea (-39, p < 0.00001), and LC13 dyspnea (-11, p < 0.0005) significantly improved at 2 and 6 weeks after intervention. Provider surveys indicated favourable ease of use. Conclusion. The new ASEPT catheter offers a safe and effective option for the management of MPE.

Does the Prevalence of Dyslipidemias Differ between Newfoundland and the Rest of Canada? Findings from the Electronic Medical Records of the Canadian Primary Care Sentinel Surveillance Network.

INTRODUCTION: Newfoundland and Labrador (NL) has the highest prevalence of cardiovascular disease (CVD) in Canada. Dyslipidemia is a risk factor for CVD. This study compares the prevalence of dyslipidemia in the NL population with the rest of Canada. METHODS: A cross-sectional study, using data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), was undertaken. The study population included adults, excluding pregnant women, aged 20 years and older. Canadian guidelines were used for classifying dyslipidemia. Univariate and multivariate analyses were conducted to compare the lipid levels and prevalence of dyslipidemia between NL and the rest of Canada. RESULTS: About 128,825 individuals (NL: 7,772; rest of Canada: 121,053) were identified with a mean age of 59 years (55% females). Mean levels of total cholesterol (4.96 vs. 4.93, p = 0.03), low-density lipoprotein (LDL) (3.00 vs. 2.90 mmol/L, p < 0.0001), triglyceride (1.47 vs. 1.41 mmol/L, p < 0.0001), and high-density lipoprotein (HDL) (1.29 vs. 1.39 mmol/L, p < 0.0001) were significantly different in NL compared to the rest of Canada. Dyslipidemias of LDL (29 vs. 25% p < 0.0001), HDL (38 vs. 27%, p < 0.0001), and triglyceride (29 vs. 26%, p < 0.0001) were significantly more common in NL. After adjustment for confounding variables, NL inhabitants were more likely to have dyslipidemia of total cholesterol (OR: 1.16, 95% CI: 1.10-1.23, p < 0.0001), HDL (OR: 1.52, 95% CI: 1.44-1.60, p < 0.0001), LDL (OR: 1.38, 95% CI: 1.30-1.46, p < 0.0001), and ratio (OR: 1.53, 95% CI: 1.42-1.60, p < 0.0001). CONCLUSION: The NL population has a significantly higher rate of dyslipidemia compared to the rest of Canada, and the mean levels of all lipid components are worse in NL. Distinct cultural and genetic features of the NL population may explain this, accounting for a higher rate of CVD in NL.

Single and mixed dyslipidaemia in Canadian primary care settings: findings from the Canadian primary care sentinel surveillance network database.

OBJECTIVES: Dyslipidaemia is a major risk factor to cardiovascular disease (CVD)--the leading cause of death worldwide. Limited data are available about the prevalence of various dyslipidaemia in Canada. The objective of this study is to describe the prevalence of various single and mixed dyslipidaemia within the Canadian population in a primary care setting. SETTING: A cross-sectional study, using the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), was undertaken. PARTICIPANTS: Non-pregnant adults older than 20 years were included. OUTCOME MEASURES: Canadian guidelines were used to define dyslipidaemia. Descriptive statistics and multivariate regression analyses were conducted to compare the prevalence of single/mixed dyslipidaemia. RESULTS: 134,074 individuals with a mean age of 59.2 (55.8% women) were identified. 34.8% of this population had no lipid abnormality, whereas 35.8%, 17.3% and 3.2% had abnormalities in one, two and three lipid components, respectively. Approximately 86% of these patients did not receive any lipid-lowering medication. Among the medication users (14%), approximately 12% were on statin monotherapy. Statin users (n=16,036) had a lower rate of low-density lipoprotein dyslipidaemia compared to non-medication users (3% vs 17%), whereas the prevalence of high-density lipoprotein (HDL) (20% vs 12%) and triglycerides (TG) (12% vs 7%) dyslipidaemia were higher in statin users. Statin users had a greater prevalence of HDL, TG and combined HDL-TG dyslipidaemia compared to non-medication users (OR 1.44, 95% CI 1.36 to 153), (OR 1.18, 95% CI 1.10 to 1.27) and (OR 1.30, 95% CI 1.22 to 1.38), respectively, (all p values<0.0001). CONCLUSIONS: One of every five patients in primary care settings in Canada is suffering from mixed dyslipidaemia. The overall prevalence of dyslipidaemia remains the same between treated and untreated groups, although the type of abnormal lipid component is considerably different. Among the CVD risk factors, obesity has the greatest effect on the prevalence of all types of dyslipidaemia.

Brick by brick: metformin for gestational diabetes mellitus?

Evaluation of: Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet. Med. 26(8), 798-802 (2009). This paper reviews a case-control study, reported by Balani et al., comparing maternal and neonatal outcomes of women treated for gestational diabetes mellitus with either metformin or insulin. A cohort of 100 women treated with metformin alone, without insulin rescue, was compared with a retrospective cohort of 100 women treated with insulin. Results favored metformin. This paper discusses issues related to the safety and efficiency of metformin treatment during pregnancy, the attitudes of pregnant women toward treatment options, public health policy and the worldwide gestational diabetes mellitus epidemic, as well as the financial burden of therapy, particularly for developing countries. It also looks at the pathophysiology of gestational diabetes mellitus and the need for clinical trial assessment of combination oral-hypoglycemic therapy.