Effect of pulmonary hypertension on outcome of pulmonary tuberculosis

BackgroundThis study performed at the National Research Institute of Tuberculosis and Lung Disease, Tehran, Iran, aimed to evaluate the effect of concomitant pulmonary hypertension on the outcome of pulmonary tuberculosis.MethodsNew cases of pulmonary tuberculosis were recruited for the study. Pulmonary hypertension was defined as systolic pulmonary arterial pressure ≥35 mm Hg estimated by transthoracic Doppler echocardiography. We assessed the relationship between pulmonary hypertension and mortality during the six-month treatment of tuberculosis.ResultsOf 777 new cases of pulmonary tuberculosis, 74 (9.5%) had systolic pulmonary arterial pressure ≥35 mm Hg. Ten of them (13.5%) died during treatment compared to 5% of cases with pulmonary arterial pressure less than 35 mm Hg (p = 0.007). Logistic regression analysis showed that pulmonary hypertension and drug abuse remained independently associated with mortality (OR = 3.1; 95% CI: 1.44–6.75 and OR = 4.4; 95% CI: 2.35–8.17, respectively).ConclusionA significant association was found between mortality and presence of pulmonary hypertension and drug abuse among new cases of pulmonary tuberculosis.     

Risk characterization for urinary tract infections in subjects with newly diagnosed type 2 diabetes

AimTo evaluate the risk of urinary tract infections (UTI) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM).MethodsSubjects aged ≥ 18 years and diagnosed with T2DM between 1/1/10 and 12/31/10 were identified using the MarketScan® databases, which are representative of the commercially insured US population and those with both Medicare and supplemental coverage. The index date was the first T2DM diagnosis date in 2010 (date randomly selected for those without T2DM). Subjects without T2DM were matched (1:1) by index date, age, gender, urban/rural location, and region. All subjects had continuous enrollment for 12 months before (baseline) and after (follow-up) the index date. UTI diagnosis was defined using ICD-9-CM codes. Measurements of glycemic control and body weight were not available. An adjusted logistic regression model assessed the likelihood of UTI.ResultsA total of 89,790 matched pairs were selected. During follow-up, a UTI diagnosis was more common in subjects with T2DM than without T2DM (9.4% vs. 5.7%; p < 0.0001). Recurrence of UTI was also more likely with T2DM (1.6% vs. 0.6%; p < 0.0001). In a logistic regression, subjects with T2DM had a greater likelihood of UTI during follow up (adjusted odds ratio [OR] = 1.54 [95% CI: 1.47–1.60]). This relationship remained after stratifying by gender.ConclusionSubjects with T2DM were more likely to experience a UTI and recurrent UTIs than subjects without T2DM during follow-up.     

Body composition and frailty profiles in Brazilian older people: Frailty in Brazilian Older People Study-FIBRA-BR

ObjectiveTo determine the association between body composition and frailty in older Brazilian subjects.Material and methodsThis is a Cross-sectional study called FIBRA-BR and developed in community Brazilian aged ≥65 (n = 5638). Frailty was assessed according to Fried et al. definition and body composition was determined by BMI, waist circumference and waist-hip ratio.ResultsThe lowest prevalence of frailty was observed in subjects with BMI between 25.0 and 29.9 kg/m². Subjects with a BMI <18.5 and those with elevated WC presented a higher risk of frailty compared to eutrophic subjects (odds ratio (OR) = 3.10; 95% CI: 2.06–4.67) and (OR = 1.15; 95% CI: 1.03–1.27), respectively. Being overweight was protective for pre-frailty (OR = 0.48; 95% CI: 0.4–0.58) and frailty (OR = 0.77; 95% CI: 0.67–0.9). Obese older people presented a higher risk of pre-frailty only (OR = 1.29; 95% CI: 1.09–1.51). Older people with high WC showed a greater proportion of frailty regardless of the BMI range.ConclusionUndernutrition is associated with pre-frailty and frailty in Brazilian elderly subjects, whereas obesity is associated only with pre-frailty. Overweight seems to have a protective effect against the syndrome. The excess of abdominal fat is associated with both profiles independent of the BMI.     

Intravenous corticosteroids in moderately active ulcerative colitis refractory to oral corticosteroids

BackgroundOral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis (UC). In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy.AimTo evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not.MethodsAll episodes of active UC admitted to three university hospitals between January 2005 and December 2011 were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids.Results110 episodes were included, 45% of which failed to outpatient oral corticosteroids (median dose 60 mg/day [IQR 50–60], median length of course 10 days [IQR 7–17]). Initial response (defined as mild severity or inactive disease at day 7 after starting intravenous corticosteroids, without rescue therapy) was achieved in 75%, with no between-group differences (78% vs. 75%). After a median follow-up of 12 months (IQR 4–24), 35% of the initial responders developed steroid-dependency and up to 13% required colectomy. Unsuccessful response to oral corticosteroids was the only factor associated with steroid-dependency in the long term (P = 0.001).ConclusionsIntravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency. Alternative therapeutic strategies should be assessed in this clinical setting.     

Venous Thromboembolism in Patients with Chronic Obstructive Pulmonary Disease

ObjectiveOur aim was to compare the clinical characteristics, prophylaxis, treatment, and outcomes of venous thromboembolism in patients with and without previously diagnosed chronic obstructive pulmonary disease.MethodsWe analyzed the population-based Worcester Venous Thromboembolism Study of 2488 consecutive patients with validated venous thromboembolism to compare clinical characteristics, prophylaxis, treatment, and outcomes in patients with and without chronic obstructive pulmonary disease.ResultsOf 2488 patients with venous thromboembolism, 484 (19.5%) had a history of clinical chronic obstructive pulmonary disease and 2004 (80.5%) did not. Patients with chronic obstructive pulmonary disease were older (mean age 68 vs 63 years) and had a higher frequency of heart failure (35.5% vs 12.9%) and immobility (53.5% vs 43.3%) than patients without chronic obstructive pulmonary disease (all P < .0001). Patients with chronic obstructive pulmonary disease were more likely to die in hospital (6.8% vs 4%, P = .01) and within 30 days of venous thromboembolism diagnosis (12.6% vs 6.5%, P < .0001). Patients with chronic obstructive pulmonary disease demonstrated increased mortality despite a higher frequency of venous thromboembolism prophylaxis. Immobility doubled the risk of in-hospital death (adjusted odds ratio, 2.21; 95% confidence interval, 1.35-3.62) and death within 30 days of venous thromboembolism diagnosis (adjusted odds ratio, 2.04; 95% confidence interval, 1.43-2.91).ConclusionPatients with chronic obstructive pulmonary disease have an increased risk of dying during hospitalization and within 30 days of venous thromboembolism diagnosis. Immobility in patients with chronic obstructive pulmonary disease is an ominous risk factor for adverse outcomes.     

Prevalencia de déficit de alfa-1 antitripsina en pacientes con EPOC en Argentina. Estudio DAAT.AR

IntroductionAlpha-1 antitrypsin deficiency (AATD) is still underdiagnosed, despite the recommendation to determine AAT in patients with chronic obstructive pulmonary disease (COPD).ObjectiveTo estimate the prevalence of AATD in COPD patients adjusted according to the population of the COPD prevalence study in Argentina (EPOC.AR).Material and methodsThis was a multicenter prospective cross-sectional study of a population aged ≥ 30 years of age diagnosed with COPD, involving AAT quantification in dry blood spot and subsequent genotyping in subjects with < 1.5 mg/dL AAT in dry blood spot (< 80 mg/dL in serum). AAT was defined as the detection of variants ZZ or SZ on genotyping. The EPOC.AR study population was used to calculate local adjusted prevalence.ResultsWe included 3,254 patients (544 with AAT < 80 mg/dL) with a spirometric diagnosis of COPD. The prevalence of AATD in the total study population was 1.29% (95% CI 0.93-1.74), of which 0.92% (95% CI 0.62-1.31) were Pi*ZZ and 0.37% (95% CI 0.19-0.64) Pi*SZ. The adjusted prevalence of AATD in COPD patients ≥ 40 years of age was 0.83% (95% CI 0.23-2.08). We found that AATD was negatively associated with age (OR 0.94; 95% CI 0.90-0.98; P = .006), smoking habit (OR 0.98; 95% CI 0.96-0.99; P = .009), and FEV₁% (OR 0.95; 95% CI 0.91-0.99; P = .015).ConclusionsThe prevalence of AATD in the adult population with COPD in Argentina is estimated to be 0.83%, which could represent 17,000 cases in our country.     

Fibrinogen-to-albumin ratio is related to the severity of coronary artery disease in chronic kidney disease patients undergoing coronary angiography

ObjectivesThis study was to explore the potential relationship between the fibrinogen-to-albumin ratio (FAR) and the presence and severity of coronary artery disease (CAD) in stage 3–5 predialysis chronic kidney disease (CKD) patients.DesignThis study included 978 patients undergoing coronary angiography (CAG). CAD was defined as the presence of obstructive stenosis > 50% of the lumen diameter in any of the four main coronary arteries. Gensini scores (GSs), left main coronary artery (LMCA) and three-vessel coronary artery disease (TVD) were used to elevate the severity of CAD.ResultsThe adjusted odds ratios of CAD were 3.059 (95% CI: 1.859–5.032) and 2.670 (95% CI: 1.605–4.441) in the third and fourth quartiles of FAR compared with the first quartile, respectively. Among 759 patients diagnosed with CAD, multivariate logistic regression analysis showed that FAR (at the 0.01 level) was significantly positively associated with the presence of LMCA (adjusted OR = 1.177, 95% CI 1.067–1.299, P = 0.001) or TVD (adjusted OR = 1.154, 95% CI 1.076–1.238, P < 0.001), and a higher GS (adjusted OR = 1.152, 95% CI 1.073–1.238, P < 0.001).ConclusionsFAR levels were independently associated with the presence and severity of CAD in stage 3–5 predialysis CKD patients.     

Clinical benefits of smoking cessation in reducing all-cause and disease-specific mortality among older people in Taiwan: A 10-year nationwide retrospective cohort study

ObjectiveTo investigate the relationship between smoking cessation and disease mortality risks among elderly Taiwanese.MethodsWe identified 1677 people aged 65 or above from the 2001 National Health Interview Survey in Taiwan (2001 NHIST) and linked with the 2000–2010 National Health Insurance Research Data (2000–2010 NHIRD) and 2001–2010 Death Registry. Subjects were classified into four groups: never smokers, current smokers, former smokers quitting less than 5 years and former smokers quitting at least 5 years. Information on medical history was drawn from 2000–2001 NHIRD. Cox proportional hazards models were used to analyze the smoking status and mortality risk.ResultsOver 10 years, incidences of all-cause death per person-year was 0.048 among the never smokers, 0.058 for current smokers and 0.057 for former smokers. Current smokers had higher risk of all-cause death (HR = 1.38, 95%CI = 1.13–1.68), all-cause cancers (HR = 1.85, 95%CI = 1.28–2.69), lung cancer (HR = 3.02, 95%CI = 1.56–5.85) and cardiovascular disease (HR = 1.71, 95%CI = 1.17–2.48) as compared to never smokers. Former smokers who quit smoking for < 5 years has higher mortality risk in lung cancer (HR = 3.89, 95%CI = 1.33–11.40), respiratory diseases (HR = 2.79, 95%CI = 1.32–5.87) and chronic obstructive pulmonary disease (COPD) (HR = 3.13, 95%CI = 1.07–9.17) as compared to never smokers. Former smokers who quit smoking for over 5 years were similar to never smokers on all-cause death, lung cancer, all-cause cancers, COPD, respiratory diseases and cardiovascular diseases.ConclusionSmoking plays a prominent role in increasing the mortality risk among the Taiwanese elderly. Disease mortality risks of elderly former smokers who quit smoking over 5 years were reduced to the same level as the never smokers.     

Proteinuria predicts 10-year cancer-related mortality in patients with type 2 diabetes

BackgroundWe conducted a cohort study to determine if proteinuria predicts cancer-related mortality in type 2 diabetic subjects.MethodsBetween July 1996 and June 2003, we enrolled 646 type 2 diabetic subjects. Participants were followed-up until December 31, 2008. The vital status was ascertained by linking records with computerized death certificates in Taiwan.ResultsDuring a median follow-up of 10.4 years, 158 subjects had died, including 59 from cancers. Subjects with proteinuria had a hazard ratio (HR) of 2.77 (95% CI 1.82–4.21) for all-cause mortality and 1.99 (95% CI 1.00–3.94) for cancer-related mortality after adjustment for demographic factors and medical conditions. Specifically, proteinuria showed a trend of increased colon cancer death. The presence of proteinuria significantly improved the predictive ability of cancer-related mortality (increase in concordance statistics or area under the ROC curve = 0.03). Patients with both proteinuria and estimated glomerular filtration rate < 60 ml/min per 1.73 m² showed higher HR for all-cause mortality than patients with proteinuria only (adjusted HRs (95% CI), 4.01 (2.42–6.67) vs. 2.69 (1.51–4.79), both p < 0.01).ConclusionsProteinuria can predict 10-year all-cause and cancer-related mortalities independently in type 2 diabetic subjects, over and above the established risk factors associated with type 2 diabetes.     

Association between habitual daytime napping and metabolic syndrome: a population-based study

ObjectiveOur objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome.Materials and MethodsWe conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported.ResultsThe prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (P < 0.0001). Increased daytime napping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (P < 0.05 for all). Multivariate adjusted logistic regression analysis revealed that, compared to the no habitual daytime napping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13–1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all P < 0.05). No statistically significant associations were detected between daytime napping hours and metabolic syndrome among the male subjects.ConclusionDaytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women.     

Metabolic syndrome and impaired health-related quality of life and in non-Hispanic White,non-Hispanic Blacks and Mexican-American Adults

ObjectiveWe examined the relationship between metabolic syndrome (MetS) and impaired health-related quality of life (HRQoL) in non-Hispanic Whites (NHW), non-Hispanic Black (NHB), and Mexican-Americans (MA).MethodsData (n = 5170) from 2009–2010 NHANES were used. Subjects perceived poor overall health (POH), poor physical health (PPH), and poor mental health (PMH) status in the past 30 days were used as indices of impaired HRQoL. Race/ethnic-specific associations between MetS and indices of HRQoL were determined using prevalence odds ratios (POR) from logistic regression models. Statistical adjustments were made for age, sex, education, marital status, income and smoking.ResultsRates of POH, PPH and PMH in the past 30 days increased linearly with increased number of components of MetS in NHW, NHB and MA. MetS was associated with increased odds of PPH in NHW (POR = 2.34; 95% CI = 1.73–3.17) and MA (POR = 1.65; 95% CI = 1.09–2.50); increased odds of PPH in NHW (POR = 1.65; 95% CI = 1.18–2.31), NHB (POR = 1.83; 95% CI = 1.01–3.35), and MA (POR = 1.67; 95% CI = 1.09–2.83); and increased odds of PMH in NHW (POR = 1.50; 95% CI = 1.08–2.08), NHB (POR = 2.28; 95% CI = 1.29–4.01), and MA (POR = 1.44; 95% CI = 0.80–2.59). Upon adjustment for other independent variables, smoking and lack of education were found associated with increased odds of impaired HRQoL.ConclusionsMetS is associated with POH, PPH, and PMH in American adults. From clinical standpoint, this study further suggests that HRQoL should be considered in the management of subjects with MetS. Robust public health programs designed to reduce the prevalence of MetS may help in reducing impaired HRQoL, including POH, PPH, and PMH in American adults who have MetS.     

Relative contributions of different cardiovascular risk factors to significant arterial stiffness

BackgroundAlthough arterial stiffness has been known to be related to many cardiovascular (CV) risk factors, the level of contribution of each risk factor to significant arterial stiffness is not yet clear.MethodsWe studied an out-patient cohort of 835 subjects who were without a history of CV disease. Brachial–ankle pulse wave velocity (baPWV) measurement and Framingham risk score (FRS) calculation were performed for all subjects.ResultsbaPWV was well correlated with FRS (r = 0.523, P < 0.001) and it could independently predict it (P < 0.001) after adjusting for the conventional CV risk factors. We defined a baPWV > 1710 cm/s as significant arterial stiffness on the basis of its ability to detect a high 10-year risk of coronary heart disease (FRS > 20%). Multiple logistic regression analysis revealed that the adjusted odds ratios of significant arterial stiffness for an age > 60 years, hypertension, male gender, smoking and diabetes were 6.2 (95% CI 4.4–8.7), 3.4 (95% CI 2.1–5.3), 1.9 (95% CI 1.3–2.8), 1.9 (95% CI 1.2–3.2) and 1.6 (95% CI 1.1–2.4), respectively. Hyperlipidemia and obesity were not statistically significant.ConclusionsOld age and hypertension were the strongest independent predictors of significant arterial stiffness. Male gender, smoking and diabetes followed in order of strength as independent predictors.     

Accuracy of computed tomography angiography in the detection of pulmonary embolism in patients with high body weight

BackgroundThe accuracy of CT pulmonary angiography (CTPA) in detecting or excluding pulmonary embolism has not yet been assessed in patients with high body weight (BW).MethodsThis retrospective study involved CTPAs of 114 patients weighing 75–99 kg and those of 123 consecutive patients weighing 100–150 kg. Three independent blinded radiologists analyzed all examinations in randomized order. Readers' data on pulmonary emboli were compared with a composite reference standard, comprising clinical probability, reference CTPA result, additional imaging when performed and 90-day follow-up. Results in both BW groups and in two body mass index (BMI) groups (BMI < 30 kg/m² and BMI ≥ 30 kg/m², i.e., non-obese and obese patients) were compared.ResultsThe prevalence of pulmonary embolism was not significantly different in the BW groups (P = 1.0). The reference CTPA result was positive in 23 of 114 patients in the 75–99 kg group and in 25 of 123 patients in the ≥ 100 kg group, respectively (odds ratio, 0.991; 95% confidence interval, 0.501 to 1.957; P = 1.0). No pulmonary embolism-related death or venous thromboembolism occurred during follow-up. The mean accuracy of three readers was 91.5% in the 75–99 kg group and 89.9% in the ≥ 100 kg group (odds ratio, 1.207; 95% confidence interval, 0.451 to 3.255; P = 0.495), and 89.9% in non-obese patients and 91.2% in obese patients (odds ratio, 0.853; 95% confidence interval, 0.317 to 2.319; P = 0.816).ConclusionThe diagnostic accuracy of CTPA in patients weighing 75–99 kg or 100–150 kg proved not to be significantly different.     

Factors predictive of macrosomia in pregnancies with a positive oral glucose challenge test: Importance of fasting plasma glucose

AimThe study aimed to determine the factors associated with fetal macrosomia following a positive oral glucose challenge test (OGCT).MethodsIn this retrospective single-centre study of 1268 pregnancies with positive 50-g OGCTs (plasma glucose ≥ 130 mg/dL, or 7.2 mmol/L), gestational diabetes mellitus (GDM) was defined as fasting plasma glucose (FPG) ≥ 95 mg/dL (5.3 mmol/L) and/or postprandial glucose (PPG) ≥ 120 mg/dL (6.7 mmol/L).ResultsIn GDM pregnancies, the odds ratios adjusted for confounders (age, BMI, ethnicity, parity and weight gain) were 2.02 for macrosomia (Z score ≥ 1.28) and 2.62 for severe macrosomia (Z score ≥ 1.88). For each 10-mg/dL increase in FPG, the mean birth–weight increase was 60 g. Macrosomia risk did not differ between GDM patients with normal FPG (< 95 mg/dL, or 5.3 mmol/L) and non-diabetics, but increased significantly in cases of FPG ≥ 95 mg/dL and regardless of the level of PPG.ConclusionIn our study population, birth–weight and macrosomia risk were strongly correlated with FPG, suggesting that it is a simple and efficient marker for the risk of macrosomia.     

Association of statin use and the risk of end-stage renal disease: A nationwide Asian population-based case–control study

BackgroundAlthough experimental models have shown that statins could alleviate glomerular damage and decrease urinary protein excretion, the renal effects of statins remain unclear. A case–control study was conducted using data from Taiwan's National Health Insurance system.MethodsAn end-stage renal disease (ESRD) group comprising 11,486 patients was established. Each patient was frequency-matched by age, sex, and comorbidities with one person without ESRD from the general population. Logistic regression analysis was performed to estimate the influence of statin use on ESRD risk.ResultsThe overall adjusted odds ratios (ORs) of ESRD among patients who received statins was 1.59 (95% confidence interval = 1.50–1.68). The raised ESRD risk of statin remained consolidated regardless of statin type (P < .001), except lovastatin. Further, while stratified by cumulative define daily dose, the risk of ESRD increased with accumulative dosage of statins (P for trend < .001).ConclusionThis population-based case–control study showed that statin use might be associated with increased ESRD risks. Large-scale randomized clinical trial encompassing statins of different kinds and populations of different comorbidities would be helpful to clarify the potential ESRD risks of statin users     

Obesity is more closely related with hepatic steatosis and fibrosis measured by transient elastography than metabolic health status

ObjectiveThe pathogenesis of non-alcoholic fatty liver disease (NAFLD) involves multiple concomitant events induced by obesity and metabolic health condition. This study aimed to assess the risk of NAFLD according to metabolic health and obesity status using transient elastography (TE).Materials and MethodsA total of 2198 asymptomatic adults without chronic liver disease and who underwent a medical health check-up were recruited. Subjects were categorized into four groups according to metabolic health and obesity statuses: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). Hepatic steatosis was defined as controlled attenuation parameter (CAP) ≥ 238 dB/m, and significant liver fibrosis was defined as liver stiffness measurement (LSM) > 7.0 kPa, as defined by TE.ResultsCompared with MHNO group, the odds ratios (ORs) [95% confidence interval (CI)] for hepatic steatosis were 2.94 [2.32–3.71], 4.62 [3.52–6.07], and 12.02 [9.08–15.92] in the MUNO, MHO, and MUO groups, respectively (P < 0.001) in crude model. Regarding liver fibrosis, there was no significant difference in the ORs in MUNO group (ORs: 0.95 [95% CI, 0.33–2.78], P value = 0.929), whereas there was a significant increase in the ORs in MHO group compared with MHNO group (ORs: 4.32 [95% CI, 1.73–10.76], P = 0.002) in the fully adjusted model.ConclusionOur results show that MHO was associated with both liver steatosis and fibrosis assessed by transient elastography. Our results suggest that a healthy metabolic profile does not protect obese adults from hepatic steatosis or fibrosis, indicating that obesity itself might contribute to liver fibrosis.     

Efficacy and safety of linagliptin in subjects with type 2 diabetes mellitus and poor glycemic control: Pooled analysis of data from three placebo-controlled phase III trials

AimsTo evaluate the efficacy/safety of dipeptidyl peptidase-4 inhibitor, linagliptin, in subjects with insufficiently controlled type 2 diabetes mellitus (T2DM), and factors influencing treatment response.MethodsPooled analysis of data from 2258 subjects in three 24-week phase III, randomized, placebo-controlled, parallel-group studies, who received oral linagliptin (5 mg/day) or placebo as monotherapy, added-on to metformin, or added-on to metformin plus sulfonylurea was performed.ResultsAmong 388 subjects with HbA1c ≥ 9.0%, adjusted mean baseline HbA1c (9.4% both groups) declined to 8.3% in linagliptin group and 9.1% in placebo group at 24 weeks (P < .0001) and adjusted mean change from baseline was 1.2% (vs. 0.4%, placebo). Linagliptin significantly lowered fasting plasma glucose levels vs. placebo (1.6 mmol/l vs. 0.4 mmol/l); treatment difference, 1.1 mmol/l (95% CI, ? 1.7 to ? 0.5). Treatment and washout of previous oral antidiabetes drugs were the only factors to independently affect HbA1c change at week 24. Adverse event rates were similar for linagliptin (61.9%) and placebo (62.7%). Hypoglycemia was rare with linagliptin monotherapy/add-on to metformin (≤ 1%) and increased when linagliptin was added to metformin plus sulfonylurea (linagliptin, 17.9% vs. placebo, 8.3%).ConclusionsLinagliptin was an effective, well-tolerated treatment in subjects with T2DM and insufficient glycemic control, both as monotherapy or added-on to metformin/metformin plus sulfonylurea.     

Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review

BackgroundSafety of long-acting beta agonists (LABA) has been questioned and recent evidence suggested a detrimental effect on asthma control as well as an increased risk of death.ObjectiveTo evaluate the safety of regular use of LABA compared with placebo or LABA added to inhaled corticosteroids (ICS) compared with ICS in persistent asthma.MethodsRandomized studies from MEDLINE, EMBASE, and Cochrane Controlled Trials Register were identified. Additionally, AstraZeneca, GlaxoSmithKline, Novartis and FDA clinical trials databases were searched. Primary outcomes were asthma exacerbations (AE) requiring systemic corticosteroids or hospitalization, life-threatening exacerbations and asthma-related deaths.ResultsWe identified 92 randomized clinical trials with 74,092 subjects. LABA (as monotherapy) reduced exacerbations requiring corticosteroids (Relative Risk [RR] = 0.80; 95% CI, 0.73–0.88), without detrimental effects on hospitalizations or life-threatening episodes. Contrarily, LABA showed a significant increase in asthma-related deaths (Relative Risk = 3.83; 95% CI, 1.21–12.14). Subgroup analysis suggests that children, patients receiving salmeterol, and a duration of treatment >12 weeks are associated with a higher risk of serious adverse effects; also there was a protective effect of concomitant use of ICS. On the other hand, combination of LABA/ICS reduced exacerbations (RR = 0.73; 95% CI, 0.67–0.79), and hospitalizations (RR = 0.58, 95% CI, 0.45–0.74). Combined therapy was also equivalent to ICS in terms of life-threatening episodes and asthma-related deaths. Again, children and use of salmeterol were associated with an increased risk of some severe outcomes as compared with adults and formoterol users, respectively.ConclusionsThis review reinforced the international recommendations in terms of the use of LABA remains the preferred add-on therapy to ICS for patients whose disease cannot adequately controlled with ICS, and that LABA cannot be prescribed as a monotherapy. Nevertheless, in spite of the protective effect of the ICS, children and salmeterol use still show an increased risk of non-fatal serious adverse events.