Prevalence and predictors of MRSA,ESBL, and VRE colonization in the ambulatory IBD population

Background and aimsInflammatory bowel disease (IBD) patients may be at increased risk of acquiring antibiotic-resistant organisms (ARO). We sought to determine the prevalence of colonization of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae containing extended spectrum beta-lactamases (ESBL), and vancomycin-resistant enterococi (VRE) among ambulatory IBD patients.MethodsWe recruited consecutive IBD patients from clinics (n = 306) and 3 groups of non-IBD controls from our colon cancer screening program (n = 67), the family medicine clinic (n = 190); and the emergency department (n = 428) from the same medical center in Toronto. We obtained nasal and rectal swabs for MRSA, ESBL, and VRE and ascertained risk factors for colonization.ResultsCompared to non-IBD controls, IBD patients had similar prevalence of colonization with MRSA (1.5% vs. 1.6%), VRE (0% vs. 0%), and ESBL (9.0 vs. 11.1%). Antibiotic use in the prior 3 months was a risk factor for MRSA (OR, 3.07; 95% CI: 1.10–8.54), particularly metronidazole. Moreover, gastric acid suppression was associated with increased risk of MRSA colonization (adjusted OR, 7.12; 95% CI: 1.07–47.4). Predictive risk factors for ESBL included hospitalization in the past 12 months (OR, 2.04, 95% CI: 1.05–3.95); treatment with antibiotics it the past 3 months (OR, 2.66; 95% CI: 1.37–5.18), particularly prior treatment with vancomycin or cephalosporins.ConclusionsAmbulatory IBD patients have similar prevalence of MRSA, ESBL and VRE compared to non-IBD controls. This finding suggests that the increased MRSA and VRE prevalence observed in hospitalized IBD patients is acquired in-hospital rather than in the outpatient setting.     

COVID-19 associated infections in the ICU setting: A retrospective analysis in a tertiary-care hospital

IntroductionOur work describes the frequency of superinfections in COVID-19 ICU patients and identifies risk factors for its appearance. Second, we evaluated ICU length of stay, in-hospital mortality and analyzed a subgroup of multidrug-resistant microorganisms (MDROs) infections.MethodsRetrospective study conducted between March and June 2020. Superinfections were defined as appeared ≥48 h. Bacterial and fungal infections were included, and sources were ventilator-associated lower respiratory tract infection (VA-LRTI), primary bloodstream infection (BSI), secondary BSI, and urinary tract infection (UTI). We performed a univariate analysis and a multivariate analysis of the risk factors.ResultsTwo-hundred thirteen patients were included. We documented 174 episodes in 95 (44.6%) patients: 78 VA-LRTI, 66 primary BSI, 9 secondary BSI and 21 UTI. MDROs caused 29.3% of the episodes. The median time from admission to the first episode was 18 days and was longer in MDROs than in non-MDROs (28 vs. 16 days, p < 0.01). In multivariate analysis use of corticosteroids (OR 4.9, 95% CI 1.4–16.9, p 0.01), tocilizumab (OR 2.4, 95% CI 1.1–5.9, p 0.03) and broad-spectrum antibiotics within first 7 days of admission (OR 2.5, 95% CI 1.2–5.1, p < 0.01) were associated with superinfections. Patients with superinfections presented respect to controls prolonged ICU stay (35 vs. 12 days, p < 0.01) but not higher in-hospital mortality (45.3% vs. 39.7%, p 0.13).ConclusionsSuperinfections in ICU patients are frequent in late course of admission. Corticosteroids, tocilizumab, and previous broad-spectrum antibiotics are identified as risk factors for its development.     

Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study

BackgroundIdentifying patients at risk of developing diabetic peripheral neuropathy (DPN) is of paramount importance in those with type 2 diabetes mellitus (T2DM) to provide and anticipate secondary prevention measures as well as intensify action on risk factors, particularly so in primary care. Noteworthy, the incidence of DPN remains unknown in our environment.Aims(i) To analyze a single angiotensin-converting enzyme (ACE) gene polymorphism (D/I) as a genetic marker of risk of developing DPN, and (ii) to determine the incidence of DPN in our environment.Research design and methodsLongitudinal study with annual follow-up for 3 years involving a group of T2DM (N = 283) randomly selected. ACE gene polymorphism distribution (I = insertion; D = deletion) was determined. DPN was diagnosed using clinical and neurophysiology evaluation.ResultsBaseline DPN prevalence was 28.97% (95% CI, 23.65–34.20). ACE polymorphism heterozygous genotype D/I presence was 60.77% (95% CI, 55.05–66.5) and was independently associated with a decreased risk of DPN (RR, 0.51; 95% CI, 0.30–0.86). DPN correlated with age (P < 0.001) but not with gender (P = 0.466) or time of evolution of T2DM (P = 0.555). Regarding end point, DPN prevalence was 36.4% (95% CI, 30.76–42.04), and accumulated incidence was 10.4% 3 years thereafter. In the final Poisson regression analysis, the presence of heterozygous genotype remained independently associated with a decreased risk of DPN (RR, 0.71; (95% CI, 0.53–0.96). DPN presence remained correlated with age (P = 0.002), but not with gender (P = 0.490) or time of evolution (P = 0.630).ConclusionsIn our series, heterozygous ACE polymorphism (D/I) stands as a protective factor for DPN development. Accumulated incidence of DPN was relevant. Further prospective studies are warranted.     

Effect modification of hyperlipidemia and hypertension on the association between type 2 diabetes and gout

AimsWe evaluated the association between type 2 diabetes and gout by a retrospective cohort study.MethodsData of 17,259 male and 18,318 female patients with type 2 diabetes were retrieved for the 1998–2010 period. These patients were matched to a comparison group (n = 34,518 and n = 36,636, respectively) in a 1:2 ratio by age and region.ResultsWe found that patients with type 2 diabetes after adjustment for hyperlipidemia and hypertension had a lower risk of incident gout than the matched population (incidence rate ratio, men: 0.39 [95% CI: 0.36–0.42]; women: 0.78 [0.72–0.84]). Specifically, type 2 diabetes alone without hyperlipidemia and hypertension was associated with a reduced risk of incident gout in men (adjusted relative risk [RR]: 0.29, 95% CI: 0.22–0.39), but not in women (0.86, 95% CI: 0.55–1.36). We found that insulin users with hyperlipidemia and hypertension associated with risk of incident gout and no sex-specific differences were noted (adjusted RR, men: 1.28 [95% CI: 1.11–1.48]; women: 1.32 [95% CI: 1.14–1.53]). Specifically, insulin users alone without hyperlipidemia and hypertension were not statistically significantly associated with gout risk (P ≥ .0954).ConclusionsThe results of this study indicated that hyperlipidemia and hypertension modified the association between type 2 diabetes and gout.     

Pregnancy complications,mental health-related problems and type 2 diabetes mellitus in Malaysian women

AimsThe aim of this study was to investigate the association between pregnancy complications, mental health-related problems, and type 2 diabetes mellitus (T2DM) in Malaysian women.Materials and methodsA case–control study of women with T2DM (n = 160) matched by age range to controls without T2DM (n = 160). Data were collected in the Negeri Sembilan and PutraJaya regions in Malaysia, from two hospital outpatient clinics, PutraJaya Hospital and Tuanku Jaa’far Hospital Seremban, and one health clinic at Seremban. Validated, interviewer-administered questionnaires were used to obtain the data. The unadjusted and adjusted estimates were calculated using the Mantel–Haenszel method.ResultsNeither depression (RR 0.74, 95% CI: 0.39–1.41) nor anxiety (RR 1.00, 95% CI: 0.53–1.88) symptoms increased the risk of T2DM significantly. However, gestational diabetes (RR 1.35, 95% CI: 1.02–1.79), and ≥3 pregnancies (RR 1.39, 95% CI: 1.08–1.79) were significant risk factors for the development of T2DM. T2DM was not a significant risk factor for either depression (RR 1.26, 95% CI: 0.91–1.74) or anxiety symptoms (RR 1.13, 95% CI: 0.59–2.19).ConclusionIn this study, T2DM is not a significant risk factor for depression and anxiety; similarly, neither are depression and anxiety significant risk factors for T2DM. Although prevalence of depression and anxiety is not alarming, the findings reported here should alert clinicians to screen and treat anxiety and depression in people with diabetes and also note the importance of monitoring women with complications in pregnancy for risk of later T2DM.     

CYP2C19*2/ABCB1-C3435T polymorphism and risk of cardiovascular events in coronary artery disease patients on clopidogrel: Is clinical testing helpful?

BackgroundStudies evaluating CYP2C19*2 and ABCB1-C3435T polymorphisms have shown conflicting results. We performed this meta-analysis to evaluate role of clinical testing for these polymorphisms in CAD patients on clopidogrel.Methods19,601 patients from 14 trials were analyzed. The endpoints were major adverse cardiovascular events (MACE), cardiovascular (CV) death, stent thrombosis (ST), myocardial infarction (MI), stroke and major bleeding. Combined relative risks (RR) with 95% confidence intervals (CI) were computed for each outcome by using standard methods of meta-analysis and test parameters were computed.ResultsCYP2C19*2 polymorphism was associated with higher risk of MACE [RR: 1.28, CI: 1.06–1.54; p = 0.009], CV death [RR: 3.21, CI: 1.65–6.23; p = 0.001], MI [RR: 1.36, CI: 1.12–1.65; p = 0.002], ST [RR: 2.41, CI: 1.69–3.41; p < 0.001]. No difference was seen in major bleeding events [RR: 1.02, CI: 0.86–1.20; p = 0.83]. Subgroup analysis showed similar results for elective PCI [RR: 1.34, CI: 1.01–1.76; p = 0.03], and PCI with DES [RR: 1.53, CI: 1.029–1.269; p = 0.03]. CYP2C19*2 polymorphism has very low sensitivity (28–58%), specificity (71–73%), positive predictive value (3–10%) but good negative predictive value (92–99%). ABCB1-C3435T polymorphism analysis revealed similar MACE [RR: 1.13, CI: 0.99–1.29; p = 0.06], ST [RR: 0.88, CI: 0.52–1.47; p = 0.63] and major bleeding [RR: 1.04, CI: 0.87–1.25; p = 0.62] in both groups.ConclusionIn CAD patients on clopidogrel therapy, CYP2C19*2 polymorphism is associated with significantly increased adverse cardiovascular events. However, due to the low positive predictive value, routine genetic testing cannot be recommended at present.     

Interleukin-18 and the risk of future cardiovascular disease among initially healthy women

ObjectiveElevated levels of interleukin (IL)-18 have been implicated in the development of atherosclerosis in animals. Data in humans are less clear, and data in women are particularly scarce.Methods and resultsIn a prospective nested case–control study of initially healthy women, we measured baseline plasma IL-18 levels in 253 participants who subsequently developed cardiovascular disease (CVD) and in 253 healthy age- and smoking-matched controls. IL-18 levels were higher at baseline among those who developed CVD (274.1 pg/mL versus 233.8 pg/mL, P < 0.001), and were associated with future CVD (relative risk (RR) for highest versus lowest quartile 2.53; 95% CI, 1.47–4.35, P < 0.001). While that risk was attenuated after adjustment for traditional cardiovascular risk factors (RR 1.60; 95% CI, 0.77–3.34, P = 0.13), those with IL-18 levels at or above a threshold of the 90th percentile (442 pg/mL) remained at elevated risk after adjustment (RR 2.40; 95% CI, 1.05–5.56, P = 0.04). Levels of IL-18 above this threshold modify the fully adjusted risk of future CVD conferred by elevated levels of total cholesterol (P_interaction = 0.02).ConclusionsIn this population of apparently healthy women, IL-18 levels associate with increased risk of cardiovascular disease, but that risk is attenuated in models adjusting for traditional cardiovascular risk factors. Very high levels of IL-18 interact with hypercholesterolemia to alter CVD risk.     

Time to antibiotics administration and outcome in community-acquired pneumonia: Secondary analysis of a randomized controlled trial

BackgroundThe association between early antibiotic administration and outcomes remains controversial in patients hospitalized for community-acquired pneumonia.MethodsWe performed a secondary analysis of a randomized controlled trial comparing two antibiotic treatment strategies for patients hospitalized for moderately severe CAP. The univariate and multivariate associations between time to antibiotic administration (TTA) and time to clinical stability were assessed using a Cox proportional hazard model. Secondary outcomes were death, intensive care unit admission and hospital readmission up to 90 days.Results371 patients (mean age 76 years, CURB-65 score ≥ 2 in 52%) were included. Mean TTA was 4.35 h (SD 3.48), with 58.5% of patients receiving the first antibiotic dose within 4 h.In multivariate analysis, number of symptoms and signs (HR 0.876, 95% CI 0.784–0.979, p = 0.020), age (HR 0.986, 95% CI 0.975–0.996, p = 0.007), initial heart rate (HR 0.992, 95% CI 0.986–0.999, p = 0.023), and platelets count (HR 0.998, 95% CI 0.996–0.999, p = 0.004) were associated with a reduced probability of reaching clinical stability. The association between TTA and time to clinical stability was not significant (HR 1.009, 95% CI 0.977–1.042, p = 0.574). We found no association between TTA and the risk of intensive care unit admission, death or readmission up to 90 days after the initial admission.ConclusionIn patients hospitalized for moderately severe CAP, a shorter time to antibiotic administration was not associated with a favorable outcome. These findings support the current recommendations that do not assign a specific time frame for antibiotics administration.     

Adiponectin Levels and Risk of Coronary Heart Disease: A Meta-analysis of Prospective Studies

BackgroundAdiponectin is the most abundant circulating protein secreted by adipocytes. There is uncertainty about the association between adiponectin levels and risk of coronary heart disease (CHD). We conducted this meta-analysis to summarize the effect of adiponectin on the risk of CHD.MethodsA comprehensive search was performed to identify all prospective studies on the association of adiponectin levels and risk of CHD. The quality of the eligible studies was evaluated by the Newcastle-Ottawa Scale. The fixed- or random-effects model was selected to pool the relative risk (RR) and 95% confidence interval (CI). Heterogeneity among studies was evaluated using Q test and the I² statistic. Publication bias was estimated using modified Egger’s linear regression test.ResultsTwelve prospective studies comprising 8 nested case-control studies and 4 cohort studies were included in the meta-analysis. A total of 14,960 participants were enrolled and 4,132 incident CHD events were observed. The pooled RR for CHD was 0.83 (95% CI, 0.69–0.98, P = 0.031). Subgroup analyses showed that the pooled RRs (95% CIs) for CHD risk were 0.78 (0.66–0.92) and 0.75 (0.59–0.94) for men and women, respectively. For studies with mean age less than 65 years, the pooled RR (95% CI) for CHD risk was 0.72 (0.59–0.87). For studies with 100 or more CHD cases, the pooled RR was marginally significant (RR = 0.83, 95% CI, 0.69–1.00; P = 0.051). No publication bias was found in our study (P = 0.911).ConclusionsThis meta-analysis showed that higher levels of adiponectin were associated with a low risk of CHD. The protective effect was consistently existed in men and women and in the middle-aged populations.     

The degree of retinopathy is equally predictive for renal and macrovascular outcomes in the ACCORD Trial

AimsDiabetic retinopathy (DR) is associated with a higher risk of renal and cardiovascular events. We sought to compare the risk for renal versus cardiovascular (CV) outcomes, stratified by retinopathy severity.MethodsACCORD was a randomized trial of people with type 2 diabetes, at high-risk for CV disease. A subgroup (n = 3,369 from 71 clinics) had stereoscopic fundus photographs graded centrally. Participants were stratified at baseline to moderate/severe DR or no/mild DR and were monitored for renal and CV outcomes at follow-up visits over 4 years. The composite renal outcome was composed of serum creatinine doubling, macroalbuminuria, or end-stage renal disease. The composite CV outcome was the ACCORD trial primary outcome. Competing risk techniques were used to estimate the relative risk (RR) of renal versus CV composite outcomes within each DR stratum.ResultsThe hazards ratio for doubling of serum creatinine and incident CV event in the moderate/severe DR versus no/mild DR strata were: 2.31 (95% CI: 1.25–4.26) and 1.98 (95% CI: 1.49–2.62), respectively. The RR of the two composite outcomes was highly similar in the no/mild DR stratum (adjusted RR at 4 years for CV versus renal events = 0.96, 95% CI: 0.72–1.28) and the moderate/severe DR stratum (adjusted RR = 0.92, 95% CI: 0.64–1.31).ConclusionsThus, in people with type 2 diabetes at high risk for cardiovascular disease, incident CV versus renal events was similar, irrespective of the severity of the DR. Further evaluation of the specificity of DR for microvascular versus macrovascular events in other populations is warranted.     

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis

BackgroundTo systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus.MethodsWe searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months.Results7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83–1.02, p = 0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI 0.85–1.06; p = 0.33), cardiovascular mortality (0.95, 95% CI 0.71–1.27; p = 0.71), stroke (0.83, 95% CI 0.63–1.10; p = 0.20), or myocardial infarction (MI) (0.85, 95% CI 0.65–1.11; p = 0.24). There was no significant increased risk of major bleeding in aspirin group (2.46, 95% CI 0.70–8.61; p = 0.16). Meta-regression suggested that aspirin agent could reduce the risk of stroke in women and MI in men.ConclusionsIn patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.     

Efficacy of tumour necrosis factor antagonists in stricturing Crohn’s disease: A tertiary center real-life experience

BackgroundStenosis is the most common complication of Crohn’s disease (CD). Long-term outcome of patients receiving tumour necrosis factor (TNF) antagonists for such disease complication is poorly understood.Methods51 CD patients (from July 2006 to November 2015) who had a diagnosis of small bowel or colonic stenosis, diagnosed by colonoscopy and/or MRI enterography, and were treated with TNF antagonists (adalimumab or infliximab) were enrolled.The primary outcome was to assess the rate of success of TNF antagonists on avoiding abdominal surgery for stricturing CD patients.Results20 patients (39.2%) underwent surgery during the follow-up period. The overall incidence of abdominal surgery was 1.8 per 100 person-months at risk, while the median time to surgery was 37.9 months. The univariable and multivariable Cox’s proportional hazards analysis of baseline parameters indicated that disease location (colonic vs ileal, HR: 28.2, 95% CI: 2.45–324, p = 0.007; ileocolonic vs ileal, HR: 3.38, 95% CI: 1.09–10.5, p = 0.035), prestenotic dilatation (per 1-mm increase, HR: 1.08, 95% CI: 1.01–1.15, p = 0.022) and the existence of non-perianal fistula (HR: 9.77, 95% CI: 2.99–31.9, p < 0.001) are independent risk factors for abdominal surgery.ConclusionsIn stricturing CD, anti-TNFs are effective in up to about two-thirds of the patients.     

Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis

BackgroundThe US Food and Drug Administration has warned that treatment with dipeptidyl peptidase (DPP)-4 inhibitors may promote serious arthralgia. However, the clinical evidence for this is relatively lacking.ObjectiveFor this reason, a systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to determine the relationship between DPP-4 inhibitors and risk of arthralgia, and also to investigate any potential risk factors.MethodsAn extensive electronic search for RCTs comparing DPP-4 inhibitors with any comparators was performed up to July 2016. Outcomes of interest were overall and serious arthralgia. Summary risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.ResultsA total of 67 RCTs (involving 79,110 patients) was ultimately included. Pooled results showed that DPP-4 inhibitors were associated with a slightly but significantly increased risk of overall arthralgia (RR: 1.13, 95% CI: 1.04–1.22; P = 0.003) and a non-significant increased risk of serious arthralgia (RR: 1.44, 95% CI: 0.83–2.51; P = 0.20). Also, subgroup analyses showed that add-on/combination therapy and longer diabetes duration (> 5 years) were possible factors associated with the increased risk of overall arthralgia.ConclusionThese findings suggest that DPP-4 inhibitors can increase the risk of arthralgia. Thus, the benefits of glycaemic control must be weighed against the risk of arthralgia when prescribing DPP-4 inhibitors. Further studies are now needed to identify and confirm these risk factors.     

Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years

ObjectivesPerinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) have been proposed as markers for diagnosis and for subtyping of inflammatory bowel disease (IBD). The aim of this study was to investigate the association of p-ANCA and ASCA with a 10-year disease outcome in terms of cumulative rate of colectomy and relapse in a population-based European inception cohort of ulcerative colitis (UC) patients.MethodsSerum samples from 432 consenting patients were analysed for p-ANCA and ASCA. The results were compared with the cumulative colectomy rate, relapsing disease and total number of relapses. We used multiple regression analyses adjusted for age, sex, residence, disease extent at diagnosis, smoking, familial IBD and drug treatment to study the relationship between serological values and disease course.ResultsThe relapse rate was higher in the p-ANCA-positive patients: 82% (95% confidence interval [CI] 75–89%) compared with 67% (CI 62–72%, p = 0.011) in the p-ANCA-negative patients. The risk of relapsing disease course was higher by a factor of 1.4 (CI 1.1–1.8, p = 0.009) for p-ANCA-positive patients than for p-ANCA-negative patients, and the corresponding relative risk (RR) for the total number of relapses was 1.9 (CI 1.7–2.1, p < 0.001). In ASCA-positive patients RR for the total number of relapses was 1.8 (CI 1.5–2.1, p < 0.001). No significant association with colectomy rate was found for the presence of either p-ANCA or ASCA.ConclusionUC patients positive for p-ANCA and possibly for ASCA may have a more unfavourable long-term disease outcome in terms of relapse than UC patients without these markers.     

Effect of thiazolidinediones on in-stent restenosis in patients after coronary stenting: a meta-analysis of randomized controlled trials

BackgroundRecent experimental studies have demonstrated that thiazolidinediones (TZDs) therapy inhibits proliferation and migration of vascular smooth muscle cells, accelerates endothelium reparation and attenuates neointimal hyperplasia. It implies that TZDs therapy may have beneficial effects on in-stent restenosis (ISR). Several small-sample clinical trials have evaluated the effect of TZDs therapy on ISR, however, the results were inconsistent across trials.Methods and resultsWe performed a meta-analysis of all relevant randomized controlled trials to evaluate the effect of TZDs therapy on in-stent restenosis in patients undergoing coronary stenting. Eight trials involving 366 patients were included in this study. TZDs therapy was associated with a significant reduction in the risk of ISR in both diabetic (RR 0.37, 95% CI 0.23–0.59; P < 0.0001) and non-diabetic patients (RR 0.16, 95% CI 0.05–0.45; P = 0.0006). TZDs therapy was associated with a significant reduction in late lumen loss (WMD ?0.54 mm, 95% CI ?0.87 mm, ?0.22 mm; P = 0.001), percent diameter stenosis (WMD ?15.7%, 95% CI ?19.4%, ?12.0%; P < 0.00001), neointimal area/volume (SMD ?0.76, 95% CI ?1.13, ?0.39; P < 0.0001) and target lesion revascularization (RR 0.32, 95% CI 0.18–0.57; P = 0.0001).ConclusionsOur study suggests that TZDs therapy is an effective strategy in preventing ISR in both diabetic and non-diabetic patients undergoing coronary stenting. More studies, especially large multi-centre RCTs, are still warranted to further clarify the anti-restenotic effect of TZDs therapy.     

Risk of cardiovascular toxicities in patients with solid tumors treated with sunitinib,axitinib, cediranib or regorafenib: An updated systematic review and comparative meta-analysis

BackgroundWe performed a systematic review and comparative meta-analysis of cardiovascular toxicities associated with sunitinib, axitinib, cediranib or regorafenib; oral multi tyrosine kinase inhibitors.Patients and methodsEligible studies included randomized phase II and III trials of patients with solid tumors on sunitinib, axitinib, cediranib or regorafenib describing daily events of hypertension, left ventricular dysfunction, bleeding or thrombosis.ResultsPatients treated with these four agents had a significantly increased risk of all-grade hypertension and bleeding. The RR of all-grade hypertension, bleeding, thrombosis and cardiac dysfunction were 2.78 (95% CI 2.03–3.81; p < 0.00001), 1.93 (95% CI 1.41–2.64; p < 0.00001), 0.85 (95% CI 0.60–1.19; p = 0.50), 2.36 (95% CI 0.95–5.87; p = 0.06), respectively. Exploratory subgroup analysis showed no effect of the agent used (sunitinib vs. axitinib vs. cediranib) in the risk of hypertension; while for bleeding, only the sunitinib subgroup RR was significant compared to axitinib or cediranib.ConclusionsOur meta-analysis has demonstrated that sunitinib, axitinib, cediranib and regorafenib are associated with a higher risk of developing all grade and high grade hypertension compared with control. While for bleeding, only the sunitinib subgroup RR was significant compared to axitinib or cediranib. Clinicians should be aware of these risks and perform regular cardiovascular monitoring.     

Association between growth hormone therapy and mortality,cancer and cardiovascular risk: Systematic review and meta-analysis

ObjectiveThe potential involvement of growth hormone therapy in tumor promotion and progression has been of concern for several decades. Our aim was to assess systematically the association between growth hormone therapy and all-cause, cancer and cardiovascular mortality, cancer morbidity and risk of second neoplasm mainly in patients treated during childhood and adolescence.DesignA systematic review of all articles published until September 2013 was carried out. The primary efficacy outcome measures were the all-cause, cancer and cardiovascular standardized mortality ratios (SMR). The secondary efficacy outcome measures were the standardized incidence ratio (SIR) for cancer and the relative risk (RR) for second neoplasms. The global effect size was calculated by pooling the data. When the effect size was significant in a fixed model we repeated the analyses using a random model.ResultsThe overall all-cause SMR was 1.19 (95% CI 1.08–1.32, p < 0.001). Malignancy and cardiovascular SMRs were not significantly increased. Both the overall cancer SIR 2.74 (95% CI 1.18–5.41), and RR for second neoplasms 1.99 (95% CI 1.28–3.08, p = 0.002), were significantly increased.ConclusionThe results of this meta-analysis may raise concern on the long-term safety of GH treatment. However, several confounders and biases may affect the analysis. Independent, long-term, well-designed studies are needed to properly address the issue of GH therapy safety.     

Risk factors for foot ulcers—A cross sectional survey from a primary care setting in Brazil

AimsTo identify the prevalence of higher risk of foot ulceration and associated factors among patients with diabetes mellitus (DM) at primary health care services.MethodsIndividuals with DM, registered at primary health care services in a municipality in southern Brazil, were interviewed and underwent foot examinations. Their risk of ulceration was classified in accordance with the recommendations of the International Working Group on the Diabetic Foot. Poisson bivariate and multivariate analyses were performed and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) were calculated.ResultsThe prevalence of higher risk of foot ulceration among the 337 interviewees was 27.9% (95% CI 23.1–32.9). The following factors were associated with this risk: having been diagnosed with DM for more than 10 years (Adjusted-PR 1.669; 95% CI 1.175–2.373; p = 0.004); having had previous diagnoses of acute myocardial infarction (Adjusted-PR 1.873; 95% CI 1.330–2.638; p < 0.001) and stroke (Adjusted-PR 1.684; 95% CI 1.089–2.604; p = 0.019); presenting interdigital mycosis (Adjusted-PR 1.539; 95% CI 1.030–2.300; p = 0.035) and calluses (Adjusted-PR 1.654; 95% CI 1.117–2.451; p = 0.012).ConclusionsThe prevalence of higher risk of ulceration was high, which reinforces the importance of continued education for health care professionals in order to prevent complications in the feet of these patients.     

Associations of symptomatic or asymptomatic peripheral arterial disease with all-cause mortality and cardiovascular mortality

BackgroundTo investigate the rate of all cause and cardiovascular mortality in patients with symptomatic or asymptomatic peripheral arterial disease (PAD) compared to those without PAD.Methods and resultsAll the subjects were inpatients at high risk of atherosclerosis and enrolled from February to November, 2006. A total of 320 were followed up until an end-point (death) was reached or until February 2010. The mean follow-up time was 37.7 ± 1.5 months. Compared with non-PAD, PAD patients had significantly higher rates of hypertension, diabetes mellitus, and smoking (P < 0.01). Those with symptomatic and asymptomatic PAD had a much higher all cause (37.5% and 23.0% vs. 12.1%) and cardiovascular mortality (18.8% and 13.8% vs. 6.7%) compared to those without PAD (P < 0.001). The symptomatic PAD patients were 1.831 times (95% CI: 1.222–2.741) as likely to die as those without PAD, and 1.646 times (95% CI: 1.301–2.083) in asymptomatic PAD patients after adjusting for other factors. Those with symptomatic or asymptomatic PAD were more than twice as likely to die of CVD as those without PAD (RR: 2.248, 95% CI: 1.366–3.698 and RR: 2.105, 95% CI: 1.566–2.831, respectively).ConclusionsPAD was associated with a higher all cause and cardiovascular mortality whether or not PAD is symptomatic.