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1.
Mycoses ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997414

RESUMO

BACKGROUND: Candidemia remains associated with high mortality and increased costs worldwide. OBJECTIVE: To assess the changes over time in the relative prevalence of non-albicans candidemia (NAC). METHODS: A systematic review, meta-analysis, and meta-regression was performed. Observational studies investigating the epidemiology of consecutive, non-selected, candidemia episodes were included. Two separated analyses were conducted: (i) whole hospital analysis; (ii) intensive care unit (ICU) analysis. RESULTS: Starting from an initial total of 7726 records, 220 studies fulfilled inclusion criteria. The pooled prevalence of NAC in whole hospitals analysis was 49.5% (95% confidence intervals [CI] 48.0-51.1, I2 93.1%), while the pooled prevalence in ICU analysis was 50.6% (95% CI 46.6-54.6; I2 86.7%). In meta-regression, a progressive increase in NAC prevalence was observed in whole hospital analysis, although it explained only a small portion of between-study variance (estimated yearly prevalence change +0.3%, 95% CI from +0.1% to +0.5%, p = 0.003; adjusted R2 3.42%) and was observed only in some continents in subgroup analyses. No relevant changes over time were observed in NAC prevalence for ICU studies. CONCLUSIONS: We registered an increasing trend in the relative prevalence of NAC, which, nonetheless, seems to be limited to some continents and to contribute only minimally to explain the observed differences in NAC prevalence across studies.

2.
Nephrol Dial Transplant ; 35(1): 138-147, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30053127

RESUMO

BACKGROUND: In non-dialysis chronic kidney disease (CKD), absolute proteinuria (Uprot) depends on the extent of kidney damage and residual glomerular filtration rate (GFR). We therefore evaluated, as compared with Uprot, the strength of association of proteinuria indexed to estimated GFR (eGFR) with end-stage renal disease (ESRD) risk. METHODS: In a multi-cohort prospective study in 3957 CKD patients of Stages G3-G5 referred to nephrology clinics, we tested two multivariable Cox models for ESRD risk, with either Uprot (g/24 h) or filtration-adjusted proteinuria (F-Uprot) calculated as Uprot/eGFR ×100. RESULTS: Mean ± SD age was 67 ± 14 years, males 60%, diabetics 29%, cardiovascular disease (CVD) 34%, eGFR 32 ± 13 mL/min/1.73 m2, median (interquartile range) Uprot 0.41 (0.12-1.29) g/24 h and F-Uprot 1.41 (0.36-4.93) g/24 h per 100 mL/min/1.73 m2 eGFR. Over a median follow-up of 44 months, 862 patients reached ESRD. At competing risk analysis, ESRD risk progressively increased when F-Uprot was 1.0-4.9 and ≥5.0 versus <1.0 g/24 h per 100 mL/min/1.73 m2 eGFR in Stages G3a-G4 (P < 0.001) and Stage G5 (P = 0.002). Multivariable Cox analysis showed that Uprot predicts ESRD in Stages G3a-G4 while in G5 the effect was not significant; conversely, F-Uprot significantly predicted ESRD at all stages. The F-Uprot model allowed a significantly better prediction versus the Uprot model according to Akaike information criterion. Net reclassification improvement was 12.2% (95% confidence interval 4.2-21.1), with higher reclassification in elderly, diabetes and CVD, as well as in diabetic nephropathy and glomerulonephritis, and in CKD Stages G4 and G5. CONCLUSIONS: In patients referred to nephrology clinics, F-Uprot predicts ESRD at all stages of overt CKD and improves, as compared with Uprot, reclassification of patients for renal risk, especially in more advanced and complicated disease.

3.
Stroke ; 51(2): 666-669, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31813360

RESUMO

Background and Purpose- The purpose of this study was to conduct a meta-analysis of CVOTs (cardiovascular outcome trials) to evaluate the effect of glucagon-like peptide-1 receptor agonists therapy in reducing the risk of stroke in patients with type 2 diabetes mellitus. Methods- PubMed and other electronic sources were searched until June 20, 2019, to identify relevant studies. Hazard ratios with 95% CIs were used as a measure of the association between use of glucagon-like peptide-1 receptor agonists and risk of stroke after pooling data across trials. Results- Seven CVOTs with 56 004 participants were identified. Use of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus was associated with 15% lower risk of nonfatal stroke (P=0.002), 19% lower risk of fatal stroke (P=0.150), and 16% lower risk of total stroke (P=0.001). There was no association between reductions of hemoglobin A1c levels or body weight and risk of stroke. Conclusions- Glucagon-like peptide-1 receptor agonists reduce the risk of nonfatal stroke in patients with T2D.

4.
Am J Kidney Dis ; 75(1): 30-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31409508

RESUMO

RATIONALE & OBJECTIVE: Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine. STUDY DESIGN: Pooled analysis of 4 Italian observational cohort studies. SETTING & PARTICIPANTS: 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR)<45mL/min/1.73m2 followed up in renal clinics. PREDICTOR: Sex. OUTCOMES: End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes. ANALYTICAL APPROACH: Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline. RESULTS: Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6±10.2 in men and 26.0±10.6mL/min/1.73m2 in women (P<0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P<0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to-1.97mL/min/1.73m2 per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m2 per year; P<0.001). Although sex differences in eGFR decline were not different across CKD stages (P=0.3), the difference in slopes between men and women was progressively larger with proteinuria >0.5g/d (P = 0.04). LIMITATIONS: Residual confounding; only whites were included. CONCLUSIONS: Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women.

5.
Work ; 64(4): 755-761, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815715

RESUMO

OBJECTIVE: To estimate the three-year cumulative risk of work-related upper limb disorders (WRULDs) in a cohort of automotive industry workers and to provide a first test of the ability of the European Assembly Worksheet (EAWS) methodology to predict WRULDs. METHODS: 292 workers were investigated by reviewing workers' medical records during the period from 2012-2015 to determine their exposure to biomechanical overload according to EAWS risk scores (0-25, low risk, Green zone; 26-50, medium risk, Yellow zone; >50, High risk; Red zone). RESULTS: The risks were 0.83%, 5.71%, and 11.88% for the Control (unexposed), Green and Yellow Groups, respectively. Only the comparison between the Yellow/Control Groups was significant (p = 0.0014). In total, we observed 17 cases of musculoskeletal disorders (MSDs) (14 symptomatic and 3 cases detected by physical examination). CONCLUSIONS: The EAWS is a useful tool for the preliminary risk assessments of biomechanical overload among automotive industry workers. The finding of mainly non-specific disorders highly suggests that health surveillance should aim to identify not only full-blown diseases but also symptomatic cases.

6.
J Viral Hepat ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834645

RESUMO

Data on the prevalence of occult HBV infection (OBI) in Western Europe and in Northern America are few; hence, we conducted a systematic review and meta-analysis. All studies included had to fulfil the following inclusion criteria: (a) they investigated the prevalence of OBI (HBV DNA in liver tissue in HBsAg-negative subjects), (b) were carried out in Western Europe and in Northern America; (c) were available as a full-text manuscript, (d) written in English and (e) published up to December 2018. The exclusion criteria were as follows: (a) meta-analyses, letters, reviews, meeting abstracts or editorial comments; (b) studies investigating HBsAg-positive patients; (c) those investigating OBI outside Western Europe and in Northern America; and (d) to avoid small sample bias in the random-effects model, those enrolling less than five subjects. Thirty-four studies met the inclusion criteria, allowing a meta-analysis on 2729 patients. The overall prevalence of OBI was 34% (95% CI = 26%-42%), 28% (CI 95%: 12%-48%) in 329 subjects without chronic liver disease and 35% (95% CI 26%-44%) in 2400 patients with chronic liver disease. The prevalence of OBI was 51% (95% CI 40%-62%) in the 823 anti-HBc-positive subjects and 19% (95% CI 10%-30%) in the 1,041 anti-HBc-negative subjects. Evaluating the data from 17 studies comparing anti-HBc-positive and negative subjects, the prevalence of OBI was higher in the 641 anti-HBc-positive subjects than in the 1041 anti-HBc-negative (prevalence ratio = 2.29; 95% CI = 1.61-3.26, P < .001). This meta-analysis showed that in HBsAg-negative subjects the prevalence of OBI was high and was associated with anti-HBc positivity.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31639119

RESUMO

OBJECTIVE: The purpose of this review is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care (benzodiazepines) compared to either the standard of care or adjunctive treatment approaches (e.g. benzodiazepines plus propofol) for the treatment of alcohol withdrawal syndrome (AWS). INTRODUCTION: Benzodiazepines have been the cornerstone of AWS therapy, but in some patients, AWS is refractory to high doses. Moreover, benzodiazepine use is burdened by excessive sedation, confusion and respiratory depression. Options for management of refractory AWS include the addition of phenobarbital, propofol and, more recently, dexmedetomidine to benzodiazepines therapy. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the intensive care unit. INCLUSION CRITERIA: This review will consider studies including patients who are 18 years or older and are diagnosed with AWS. The exclusion criteria are a history of psychoactive substances or withdrawal states and/or severe neurologic disorder (e.g. traumatic brain injury, acute stroke, severe dementia, seizure disorder). METHODS: This review will include only studies published in English, with no restrictions on the year of publication. Both randomized controlled trials and observational studies (including cohort and case-control studies) assessing the drug effectiveness and safety will be included. The databases utilized will include: PubMed, Embase and Cochrane Central Register of Controlled Trials. In addition, the trial registers to be searched will include: World Health Organization International Clinical Trials Registry Platform (ICTRP), United States National Library of Medicine Drug Information Portal and ClinicalTrials.gov. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018084370.

8.
Dermatology ; 235(6): 463-470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586999

RESUMO

INTRODUCTION: Acne is a common skin disease with important psychosocial impact. Often inadequate compliance affects the efficacy of the therapy. Because of emerging use of mobile and electronic health technology, the recent literature evaluated the helpfulness of the tools in medication adherence. The first goal of our study was to evaluate the adherence to therapy with topical adapalene 0.3%/benzoyl peroxide (A-BPO) 2.5% in different groups of patients who received explicative information supported by different strategies. The second goal was to evaluate the patient's quality of life and skin parameters. MATERIALS AND METHODS: We enrolled 126 subjects with mild to severe acne vulgaris. They were randomized into 3 groups of 42 patients each and applied daily topical A-BPO (0.3%, 2.5%) for 12 weeks. The first group (G1) was trained on the gel application by an explicative leaflet. The second group (G2) received the same instructions as group 1 and a daily SMS to remind them of the application of the product. The third group (G3) only received standard instructions. Evaluations were performed at the beginning of treatment (T0) and after 12 weeks (T1): assessment of acne severity using the Investigator's Global Assessment (IGA) Scale for Acne Severity, quality of life by the Cardiff Acne Disability Index (CADI) and the Patient-Doctor Relationship Depth-of-Relationship Scale (PDRDS), skin pH, grade of hydration and adherence to treatment with a 7-day recall calendar were also measured. RESULTS: After 12 weeks of therapy, we observed a reduction in IGA in all groups confirming the clinical efficacy of the product. In the multiple comparison analysis of IGA score reduction, a significant difference was found in G2 versus G1 and G2 versus G3, while the G1 versus G3 comparison was not statistically significant. However, the leaflet group (G1) showed better results compared to the no-leaflet group (G3). Supporting these data, we observed that adherence days correlated positively with the improvement of the single parameters. Moreover, we observed that SMS and leaflet groups had a greater improvement in quality of life evaluated by CADI and PDRDS scores. CONCLUSIONS: According to our data, this experimental setup based on text message service and leaflet service is inexpensive and easy to use. Physicians could consider using these items in their practice to enhance patient adherence and satisfaction as well as treatment outcome.

9.
BMC Cancer ; 19(1): 899, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500586

RESUMO

BACKGROUND: Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. METHODS/DESIGN: CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses' duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients' cetuximab-mediated ADCC and characterize the tumor microenvironment. DISCUSSION: The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results' interpretation as well as provide new insights in host-tumor interactions and cetuximab activity. TRIAL REGISTRATION: The CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number ( NCT03874062 ).

10.
Am J Clin Nutr ; 110(5): 1220-1230, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31435641

RESUMO

BACKGROUND: The relation of dairy product consumption to health and mortality is controversial. OBJECTIVES: We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy study. METHODS: Dairy product consumption was assessed by validated semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex and adjusted for confounders estimated associations of milk (total, full fat, and reduced fat), yogurt, cheese, butter, and dairy calcium consumption with mortality for cancer, cardiovascular disease, and all causes. Nonlinearity was tested by restricted cubic spline regression. RESULTS: After a median follow-up of 14.9 y, 2468 deaths were identified in 45,009 participants: 59% from cancer and 19% from cardiovascular disease. No significant association of consumption of any dairy product with mortality was found in the fully adjusted models. A 25% reduction in risk of all-cause mortality was found for milk intake from 160 to 120 g/d (HR: 0.75; 95% CI: 0.61, 0.91) but not for the highest (>200 g/d) category of intake (HR: 0.95; 95% CI: 0.84, 1.08) compared with nonconsumption. Associations of full-fat and reduced-fat milk consumption with all-cause and cause-specific mortality were similar to those for milk as a whole. CONCLUSIONS: In this Italian cohort characterized by low to average milk consumption, we found no evidence of a dose-response association between milk consumption and mortality and also no association of consumption of other dairy products investigated with mortality.

11.
Diabetes Obes Metab ; 21(11): 2576-2580, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31373167

RESUMO

A meta-analysis of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta-analysis of available trial data was undertaken, using a random-effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP-1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80-0.96; P = 0.011) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP-1RA also reduced the risk of cardiovascular death by 12%, of non-fatal stroke by 16%, of hospitalization for heart failure by 9%, of all-cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68-0.86]; P = 0.003). GLP-1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease.

12.
Sci Rep ; 9(1): 10953, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358904

RESUMO

Extended right or left hemicolectomy are the most common surgical treatments for splenic flexure colon cancer. Extended resection (including distal pancreasectomy and/or splenectomy), has been often indicated for the treatment for the splenic flexure cancer, because the lymphatic drainage at this site is poorly defined and assumed as heterogeneous. Between January 2006 and May 2016, 103 patients with splenic flexure colon cancer were enrolled in the study. We evaluated the clinicopathological findings and outcomes of all patients and associated them to the different surgical treatment. Out of 103 selected cases an extended right hemicolectomy was performed in 22 (21.4%) patients, an extended left hemicolectomy in 24 (23.3%) patients, a segmental resection of the splenic flexure in 57 (55.3%) patients; the combined resection of adjacent organs showing tumor adherence was carried out in 11 (10.7%) patients. The tumor infiltrated near organs (T4) in 5 patients. No significant differences in complications were found among the three groups. In all groups no differences were found in the total number of harvested lymphnodes. After a median follow-up of 42 months, 30 recurrences and 19 deaths occurred (12 for tumor progression). There was no difference in overall and progression free survival among the three different surgical treatments. According to our results, the partial resection of splenic flexure was not associated with a worse prognosis and it was leading for a satisfactory oncological outcome. It is our opinion that the extended surgery is seldomly indicated to cure splenic flexure cancer.

13.
J Am Heart Assoc ; 8(12): e012356, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31166153

RESUMO

Background The value of glycemic control and preexisting cardiovascular disease in determining the risk of major cardiovascular events (MACE) in type 2 diabetes mellitus is uncertain. Intensive glucose control trials suggest that the 9% lower risk of MACE associated with intensive glycemic control, as compared with conventional glycemic control, is only driven by patients with type 2 diabetes mellitus without cardiovascular disease at baseline. Methods and Results We did a meta-analysis of cardiovascular outcome trials dividing patients with or without preexisting cardiovascular disease; we found that the lower risk of MACE is confined to patients with cardiovascular disease at baseline. Compared with placebo, the use of both glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors was associated with a significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease ( P for interaction=0.021). The meta-regression analysis of all 12 trials demonstrated a significant ( P=0.002) association between reductions of glycated hemoglobin in glycated hemoglobin A1C. Accordingly, the reduction of MACE expected if all cardiovascular outcome trials had achieved a 0.9% glycated hemoglobin reduction would have been 33%. Routine clinical care data complement the results of cardiovascular outcome trials but with some differences: the lower risk of MACE with sodium-glucose cotransporter-2 inhibitor use is evident in patients with type 2 diabetes mellitus with or without preexisting cardiovascular disease. Conclusions Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists should be included in the therapeutic plan of patients with type 2 diabetes mellitus and overt cardiovascular disease, with due attention paid to improvement of glycemic control, which may amplify their benefit on MACE.

14.
Diabetes Res Clin Pract ; 154: 101-115, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31238059

RESUMO

We provided an updated systematic review with meta-analysis of randomized controlled trials (RCTs) assessing the metabolic effects of combination therapy of insulin and GLP-1RA (combo) in comparison with other injectable therapy. We searched PubMed, Cochrane Register of Controlled Trials, Scholar, and ClinicalTrials.gov for RCTs evaluating changes in HbA1c (primary outcome), proportion of patients at HbA1c target <7%, hypoglycaemia, and weight change (secondary end-points). We included 36 RCTs involving 14,636 patients. Compared with comparator therapies (overall analysis), the combo led to a significant HbA1c reduction (=-0.49%, 95% CI -0.61 to -0.38%, P < 0.001), more patients at HbA1c target [relative risk, (RR) = 1.77, 95% CI, 1.56, 2.01, P < 0.001], similar hypoglycaemic events (RR = 1.03, 95% CI, 0.88, 1.19, P = 0.728), and reduction in body weight (-2.5 Kg, 95% CI -3.1 to -1.8 kg, P < 0.001), with high heterogeneity in each analysis. The quality of the evidence was low for three of the considered outcomes. Compared with intensified insulin regimens (basal-plus/basal-bolus) the combo produced similar glycemic control with reduction of both hypoglycaemia, and body weight. Combination therapy of GLP-1RA and insulin could represent a valuable treatment strategy to improve glycemic control in the management of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Quimioterapia Combinada , Humanos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
JBI Database System Rev Implement Rep ; 17(10): 2159-2164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31232889

RESUMO

OBJECTIVE: The purpose of this review is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care (benzodiazepines) compared to either the standard of care or other adjunctive treatment approaches (e.g. benzodiazepines plus propofol) for the treatment of alcohol withdrawal syndrome (AWS). INTRODUCTION: Benzodiazepines have been the cornerstone of AWS therapy, but in some patients, AWS is refractory to high doses. Moreover, benzodiazepine use is burdened by excessive sedation, confusion and respiratory depression. Options for management of refractory AWS include the addition of phenobarbital, propofol and, more recently, dexmedetomidine to benzodiazepines therapy. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the intensive care unit. INCLUSION CRITERIA: This review will consider studies including patients who are 18 years or older and are diagnosed with AWS. The exclusion criteria are a history of psychoactive substances or withdrawal states and/or severe neurologic disorder (e.g. traumatic brain injury, acute stroke, severe dementia, seizure disorder). METHODS: This review will include only studies published in English, with no restrictions on the year of publication. Both randomized controlled trials and observational studies (including cohort and case-control studies) assessing the drug effectiveness and safety will be included. The databases utilized will include: PubMed, Embase and Cochrane Central Register of Controlled Trials. In addition, the trial registers to be searched will include: World Health Organization International Clinical Trials Registry Platform (ICTRP), U.S. National Library of Medicine Drug Information Portal and ClinicalTrials.gov. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018084370.

16.
Endocrine ; 65(1): 15-24, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028667

RESUMO

AIM: We performed a meta-analysis of randomized controlled trials (RCTs) that evaluated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2i) on heart failure (HF) risk in patients with type 2 diabetes (T2D). METHODS AND RESULTS: The electronic search was carried out until 10 November 2018. RCTs were included if they compared add-on therapy with any DPP-4i, GLP-1 RAs, or SGLT-2i with placebo, and included in the outcome hospitalization for HF, and other outcomes required for cardiovascular safety studies. Risk of HF was the primary outcome for this meta-analysis. We used a random-effect model to calculate hazard ratio (HR) and 95% CI. Twelve trials were identified, involving 120,765 patients. Compared with placebo, HF risk showed a non-significant 10% reduction with the newer anti-hyperglycemic drugs (HR = 0.90, 0.80-1.01); use of DPP-4i and GLP-1 RAs was associated with nonsignificant modifications of the HF risk (+5% and -9%, respectively), while the use of SGLT-2i was associated with a significant 31% reduction of the HF risk (HR = 0.69, 0.61-0.79, P < 0.001), with no heterogeneity (I2 = 0%, P = 0.741), suggesting a class effect. The meta-regression analysis of all 12 trials showed no association of reductions of hemoglobin A1C with HF risk. CONCLUSION: In T2D, SGLT-2i can reduce the risk of HF that is unrelated to improved glycemic control; DPP-4i and GLP-1 RAs behave as neutral.

17.
J Cancer Res Clin Oncol ; 145(4): 921-926, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825028

RESUMO

PURPOSE: The European Association of Urology (EAU) guidelines for penile cancer (PC) are exclusively based on retrospective studies and have low grades of recommendation. The aim of this study was to assess the adherence to guidelines by investigating the management strategies for primary tumours and inguinal lymph nodes. METHODS: We retrospectively reviewed the clinical charts of 176 PC patients who underwent surgery in eight European centres from 2010 to 2016. The stage and grade were assessed according to the 2009 AJCC-UICC TNM classification system. To assess adherence rates, we compared theoretical and practical adherence to the EAU guidelines. RESULTS: Overall, 176 patients were enrolled. Partial amputation was the most frequent surgical approach (39%). 53.7% of tumours were stage Tis-T1b and the remaining 46.3% were stage T2-T4. Palpable lymph nodes were detected in 30.1% of patients and 45.1% underwent lymphadenectomy (LY). A sizeable group of tumours (43.2%) were N0. For primary treatment, adherence to the EAU guidelines was good (66%). In non-adherent cases, reasons for discrepancy were patient's choice (17%), surgeon's preference (36%), and other causes (47%). For LY, the guideline adherence was 70%, with either patient's or surgeon's choice or other causes accounting for discrepancy in 28, 20, and 52% of non-adherent cases, respectively. CONCLUSION: Adherence to the EAU guidelines for PC was quite high across the eight European centres involved in the study. This notwithstanding, strategies for further improvement should be developed and evenly adopted.


Assuntos
Fidelidade a Diretrizes , Neoplasias Penianas/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/normas , Idoso , Amputação/métodos , Amputação/normas , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Europa (Continente) , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
18.
Thorac Cancer ; 10(4): 631-641, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30806017

RESUMO

BACKGROUND: To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. METHODS: This was a double-blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end-point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser-evoked potential (secondary end-points). RESULTS: A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser-evoked potential. CONCLUSIONS: The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post-thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies.

19.
J Nephrol ; 32(3): 429-435, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30673974

RESUMO

BACKGROUND: The Systolic Blood Pressure Intervention Trial-CKD substudy (SPRINT-CKD) has suggested a lower blood pressure (BP) target in CKD patients. However, it is questionable whether the SPRINT-CKD results may be generalized to CKD patients under nephrology care. METHODS: To compare SPRINT-CKD cohort versus referred CKD patients in terms of patients' risk profile and outcomes, we pooled four prospective cohorts of consecutive CKD patients referred to 40 Italian renal clinics. We implemented the same inclusion/exclusion criteria adopted in SPRINT and same endpoints: (1) a composite of fatal and non-fatal cardiovascular (CV) events (2) all-cause mortality and (3) ESRD (composite of chronic dialysis, transplantation or 50% eGFR decline). Findings were compared with those attained in the control arm of SPRINT-CKD trial that mirrored standard BP management in clinical practice. RESULTS: Out of 2847 patients referred to renal clinics, only 20.1% (n = 571) were identified as eligible for SPRINT-CKD. Age (72 ± 9 years), gender (42.2% female) and systolic BP (142 ± 10 mmHg) did not differ from the SPRINT-CKD while referred patients had a worse risk profile at baseline: larger prevalence of prior CV disease (25.7% versus 19.5%), higher Framingham risk score (31.9 ± 14.6% versus 27.2 ± 24.7%) and lower GFR (38 ± 11 versus 48 ± 10 mL/min/1.73 m2). During 4.0 years of follow-up, 86 CV events (50 fatal), 78 all-cause death and 59 ESRD occurred with annual incidence rates higher than those observed in the SPRINT-CKD control group (CV events 4.18 vs 3.19; all-cause death 3.64 vs 2.21; ESRD 2.80 vs 0.41%/year). CONCLUSIONS: The SPRINT-CKD cohort is poorly representative of the CKD population under nephrology care, thus suggesting that conclusions may not apply to patients referred to nephrologist.

20.
J Nephrol ; 32(5): 823-836, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30604150

RESUMO

BACKGROUND: Incremental dialysis may preserve residual renal function and improve survival in comparison with full-dose dialysis; however, available evidence is limited. We therefore compared all-cause mortality and residual kidney function (RKF) loss in incremental and full-dose dialysis and time to full-dose dialysis in incremental hemodialysis (IHD) and incremental peritoneal dialysis (IPD). METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with ESRD starting IHD and IPD. We identified in PubMed and Web of Science database all cohort studies evaluating incremental dialysis evaluating three outcomes: all-cause mortality, RKF loss, time to full dialysis. IPD was defined as < 3 daily dwells in Continuous Ambulatory Peritoneal Dialysis and < 5 sessions per week in Automated Peritoneal Dialysis, while IHD was defined as < 3 HD sessions per week. RESULTS: 22 studies (75,292 participants), 15 in HD and 7 in PD, were analyzed. Mean age at dialysis start was 62 and 57 years in IHD and IPD subjects, respectively. When compared to full dose, incremental dialysis (IHD or IPD) had an overall mortality risk of 1.14 [95% CI 0.85-1.52] with high heterogeneity among studies (I2 86%, P < 0.001), and lower mean RKF loss (- 0.58 ml/min/months, 95% CI 0.16-1.01, P = 0.007). Overall, time to full-dose dialysis was 12.1 months (95% CI 9.8-14.3) with no difference between IHD and IPD (P = 0.217). CONCLUSIONS: Incremental dialysis allows longer preservation of RKF thus deferring full-dose dialysis, by about 1 year in HD and PD, with no increase in mortality risk. Large and adequate studies are needed to confirm these findings.

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