The systemic impact of non-surgical treatment of peri-implantitis with or without adjunctive systemic metronidazole: Secondary analysis of a randomized clinical trial.

OBJECTIVES: The aim of this study was to evaluate the systemic effect of non-surgical peri-implantitis treatment (NSPIT) with or without the administration of systemic metronidazole. METHODS: In this secondary analysis from a previously published clinical trial (NCT03564301), peri-implantitis patients were randomized into two groups: test, receiving NSPIT plus 500 mg of oral systemic metronidazole three times a day for 7 days (n = 10); and control group, receiving NSPIT plus placebo (n = 11). Serum samples were obtained at baseline, 3 and 6 months after therapy to determine levels of inflammatory biomarkers, lipid fractions and complete blood counts. RESULTS: Both treatment modalities produced improvements in clinical and radiographic parameters. After 6 months from NSPIT, a substantial reduction in C-reactive protein (6.9 mg/dL; 95% CI: 3.7 to 9.9, p < .001) and low-density lipoprotein cholesterol (21.8 mg/dL; 95% CI: -6.9 to 50.5, p = .013) as well as a modest increase in neutrophils counts (0.4 × 103/µL; 95% CI: -0.4 to 1.1, p = .010) was observed in the control group while the test group showed a significant reduction of TNF-α (110.1; 95% CI: 38.9 to 181.4, p = .004). CONCLUSIONS: NSPIT showed a short-term beneficial systemic effect regardless of adjunctive use of systemic metronidazole.

Critical review on bone grafting during immediate implant placement.

In the last 20 years, immediate implant placement has been proposed as a predictable protocol to replace failing teeth. The research conducted in preclinical and clinical studies have focused on soft and hard tissue changes following tooth extraction and immediate implant placement. Different approaches for hard and soft tissue grafting together with provisional restorations have been proposed to compensate tissue alterations. This review analyzed some relevant clinical and preclinical literature focusing on the impact of bone grafting procedures on immediate implant placement in terms of hard and soft tissue changes, aesthetic results, and patient-related outcomes.

Efficacy of adjunctive measures in the non-surgical treatment of peri-implantitis: A systematic review.

AIM: The aim of this systematic review was to evaluate the efficacy of patient-performed or administered adjunctive measures to non-surgical peri-implantitis therapy in terms of probing depth (PD) and/or bleeding on probing (BoP) reductions. MATERIALS AND METHODS: Randomized and controlled clinical trials with at least 6 months of follow-up were searched in three databases. Secondary outcomes included implant loss, disease resolution, recurrence of peri-implantitis, need of re-treatment, changes in marginal bone levels, patient-reported outcomes and adverse effects. RESULTS: Of 567 titles, 10 publications, reporting 9 investigations, were included. Three types of adjunctive measures were found (local/systemic antimicrobials and probiotics). Four studies evaluated the effects of local antimicrobials (i.e., minocycline microspheres, chlorhexidine chips or a metronidazole + amoxicillin gel), three studies evaluated systemic antimicrobials (either amoxicillin + metronidazole or metronidazole alone) and two studies evaluated probiotics (Lactobacillus reuteri strains). The addition of local antimicrobials led to modest improvements in PD reduction. Systemic antimicrobials showed significantly greater reductions in PD and BoP, especially at initially deep sites (PD > 6 mm). Due to the large heterogeneity among included studies, no meta-analyses were performed. CONCLUSIONS: Different adjunctive measures in the non-surgical treatment of peri-implantitis have different impact in terms of PD and BoP reductions. Improved PD reductions result after the use of systemic antimicrobials, and to a lesser extent, after the use of local antimicrobials.

Association between periodontitis and peripheral markers of innate immunity activation and inflammation.

BACKGROUND: Immune response leading to increased systemic inflammation is one of the mechanisms linking periodontitis to chronic inflammatory diseases. The aim of this study was to compare the expression of toll-like receptors 2 and 4 in monocytes and neutrophils (TLR2M, TLR2N, TLR4M, and TLR4N) and its endogenous ligands (cellular fibronectin [cFN] and heat shock protein 60 [HSP60]) in patients with and without periodontitis. Additionally, the relationship between cFN and HSP60 expression with innate immunity activation and systemic inflammatory response (interleukin 6 [IL-6]) was also evaluated. METHODS: A case-controlled study was designed in which 30 patients with periodontitis (cases) and 30 age- and sex-matched participants without periodontitis (controls) were included. Fasting blood samples were collected to determine: (1) expression of TLR2N, TLR2M, TLR4N, and TLR4M by flow cytometry; and (2) serum concentrations of cFN, HSP60, and IL-6 by ELISA technique. RESULTS: Expression of TLR2M (411.5 [314.2, 460.0] vs. 236.5 [204.0, 333.0] AFU), TLR2N (387.0 [332.0, 545.5] vs 230.0 [166.2, 277.7] AFU), TLR4M (2478.5 [1762.2, 2828.0] vs 1705.0 [1274.5, 1951.2] AFU), and TLR4N (2791.0 [2306.7, 3226.2] vs. 1866.0 [1547.5, 2687.2] AFU) as well as serum levels of cFN (301.1 [222.2, 410.9] vs. 156.4 [115.3, 194.0] ng/ml) and IL-6 (10.4 [6.5, 11.5] vs. 3.5 [2.6, 4.9] pg/ml) were significantly higher in periodontitis patients than those without periodontitis. A positive association was found between periodontitis and cFN (odds ratio [OR] = 1.028, p < 0.001), TLR2N (OR = 1.026, p < 0.001), TLR4M (OR = 1.001, p = 0.002), and IL-6 (OR = 1.774, p < 0.001). CONCLUSIONS: Periodontitis patients exhibited high expression of TLRs, cFN, and IL-6.

The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupted in patients with rheumatoid arthritis.

BACKGROUND: Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA. METHODS: Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis. RESULTS: Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213-376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7-4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. -174 [95% CI -213 to -135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment. CONCLUSION: The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.

Comparison of clinical outcomes of immediate versus delayed placement of dental implants: A systematic review and meta-analysis.

OBJECTIVE: Two focused questions were addressed: Focused question (Q1) 1) Are there any differences between immediate and delayed placement in terms of (i) survival rate, (ii) success rate, (iii) radiographic marginal bone levels, (iv) height/(v)thickness of buccal wall, (vi) peri-implant mucosal margin position, (vii) aesthetics outcomes and (viii) patient reported outcomes? Focused question 2 (Q2) What is the estimated effect size of immediate implant placement for all parameters included in Q1? MATERIALS AND METHODS: An electronic search (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials and OpenGray) and hand search were conducted up to November 2019. Randomised controlled trials (RCT) with delayed implant placement as controls were eligible in the analysis for Q1. Immediate dental implant arms RCTs, controlled clinical trials (CCTs) and prospective case series of immediate implant placement were eligible in the analysis for Q2. RESULTS: Six papers (RCTs) were included in the analysis for Q1 and 53 papers (22 RCTs, 11 CCTs and 20 case series) for Q2. Q1: Meta-analyses did not show any significant difference in implant survival, but it did for bone levels and PES scores at 1 year post-loading, favouring the immediate group. Q2: Meta-analyses showed that immediate implants had a high survival rate (97%) and presented high PES scores (range 10.36 to 11.25). Information regarding marginal bone loss and gingival/papillary recession varied among all included studies. CONCLUSION: Similar survival rate was found between immediate and delayed implants. Immediate implants presented threefold early complications and twofold delayed complications. Success criteria should be reported more consistently, and the incidence/type of complications associated with immediate implants should be further explored.

Adjunctive benefits of systemic metronidazole on non-surgical treatment of peri-implantitis. A randomized placebo-controlled clinical trial.

AIM: To study clinical, radiographic, and microbiological outcomes after non-surgical therapy of peri-implantitis with or without adjunctive systemic metronidazole. MATERIALS AND METHODS: A randomized placebo-controlled clinical trial was carried out in 32 subjects (62 implants) diagnosed with peri-implantitis. Implants received a mechanical non-surgical debridement session and systemic metronidazole or placebo. Clinical, radiographic, and microbiological outcomes were evaluated at baseline, 3, 6, and 12 months. RESULTS: After 12 months, the test treatment resulted in significantly greater PPD reduction (2.53 vs. 1.02 mm) and CAL gain (2.14 vs. 0.53 mm) (p value <.05) in comparison with placebo. The test treatment also resulted in additional radiographic bone gain (2.33 vs. 1.13 mm) compared with placebo (p value <.05). There was a significantly greater decrease in Porphyromonas gingivalis, Tannerella forsythia, and Campylobacter rectus counts compared with the control group (p value <.05). At the end of follow-up, 56.3% of patients met the success criteria in the test group and 25% in the control group. CONCLUSIONS: The use of systemic metronidazole as an adjunct to non-surgical treatment of peri-implantitis resulted in significant additional improvements in clinical, radiographic, and microbiological parameters after 12 months of follow-up. This study is registered in ClinicalTrials.gov (NCT03564301).

Peri-implantitis, systemic inflammation, and dyslipidemia: a cross-sectional biochemical study.

PURPOSE: The aim of this study was to compare the inflammatory and lipid profile of patients with and without peri-implantitis. METHODS: A cross-sectional biochemical study was carried out in which blood samples were collected from 16 patients with peri-implantitis and from 31 subjects with healthy implants. Clinical peri-implant parameters were obtained from all subjects. Levels of tumor necrosis factor-alpha and interleukin-10 (IL-10) were measured in serum. Lipid fractions, glucose and creatinine levels, and complete blood count were also assessed. RESULTS: After controlling for a history of periodontitis, statistically significant differences between peri-implantitis patients and controls were found for total cholesterol (estimated adjusted mean difference, 76.4 mg/dL; 95% confidence interval [CI], 39.6, 113.2 mg/dL; P<0.001), low-density lipoprotein (LDL) cholesterol (estimated adjusted mean difference, 57.7 mg/dL; 95% CI, 23.8, 91.6 mg/dL; P<0.001), white blood cells (WBC) (estimated adjusted mean difference, 2.8×103/µL; 95% CI, 1.6, 4.0×103/µL; P<0.001) and IL-10 (estimated adjusted mean difference, -10.4 pg/mL; 95% CI, -15.8, -5.0 pg/mL; P<0.001). The peri-implant probing pocket depth (PPD) was modestly positively correlated with total cholesterol (r=0.512; P<0.001), LDL cholesterol (r=0.463; P=0.001), and WBC (r=0.519; P<0.001). A moderate negative correlation was observed between IL-10 and PPD (r=0.609; P<0.001). CONCLUSIONS: Otherwise healthy individuals with peri-implantitis showed increased low-grade systemic inflammation and dyslipidemia.

Proprotein convertase subtilisin/kexin type 9 in the dyslipidaemia of patients with axial spondyloarthritis is related to disease activity.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism and has been linked to cardiovascular (CV) risk. The purpose of the present study was to examine whether PCSK9 levels are related to abnormalities in the lipid profile and the development of atherosclerosis that occurs in patients with axial SpA (axSpA). METHODS: We performed a cross-sectional study that encompassed 545 individuals; 299 patients with axSpA and 246 statin use-matched controls. PCSK9 and standard lipid profiles were analysed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the influence of PCSK9 on axSpA-related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: Total cholesterol, high-density lipoprotein and low density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein A1 were significantly lower in axSpA patients than controls. PCSK9 serum levels [ß coefficient -44 ng/dl (95% CI -60, -27), P = 0.000] were also downregulated in axSpA patients after fully multivariable adjustment. ASDAS-CRP was found to be independently and significantly related to PCSK9 [ß coefficient 10 ng/dl (95% CI 1, 18), P = 0.023] after analysing fully adjusted models that took age, sex and the rest of the lipid profile molecules into account. Whereas patients taking prednisone showed higher serum levels of PCSK9 [55 ng/ml (95% CI 24, 8), P = 0.001], those under anti-TNF-α therapies exhibited lower levels [ß coefficient -26 ng/ml (95% CI -43, -9], P = 0.003]. CONCLUSION: PCSK9 is downregulated in patients with axSpA. Disease activity is positive and significantly related to PSCK9. Anti-TNF-therapy yields a reduction in PCSK9 serum levels.

Hepatitis C virus media coverage favorably impacts on antibody testing in the non-interferon era.

BACKGROUND: In the non-interferon era, many patients still remain untested for hepatitis C virus (HCV) infection. Our aim was to determine if media coverage, number and type of news, can influence the rate of HCV testing. METHODS: For each calendar year we searched from national, regional and local newspapers for articles published related to HCV between 2001 and 2013 (interferon era) and 2014-2018 (non-interferon era) and the HCV tests performed. Demographics, provider data and test result were collected from patients tested. RESULTS: During the studied period, 21 913 press articles were found, and we identified a total of 293 226 HCV tests. A total of 9778 HCV tests from 5237 patients tested positive (1.88%). An inverse correlation was found between media coverage and the number of HCV tests during the interferon era (r2 = -0.558, P = 0.024), where news concerning epidemiology and burden of the disease were more frequent. By contrast, in the non-interferon era a strong correlation was observed (r2 = 0.900, P = 0.019), where news related to treatment prevailed. CONCLUSION: Our results show that media coverage on HCV fluctuate so the type of news. It remains to be prospectively evaluated if well designed publicity campaigns about the benefits of HCV screening and treatment influences on HCV testing.

Differences in the periodontal microbiome of successfully treated and persistent aggressive periodontitis.

AIMS: The primary aim of this investigation was to analyse the periodontal microbiome in patients with aggressive periodontitis (AgP) following treatment. METHODS: Sixty-six AgP patients were recalled on average 7 years after completion of active periodontal treatment and had subgingival plaque samples collected and processed for 16S rRNA gene sequencing analyses. RESULTS: Of 66 participants, 52 showed persistent periodontal disease, while 13 participants were considered as "successfully treated AgP" (no probing pocket depths >4 mm) and 1 was fully edentulous. Genera associated with persistent generalized disease included Actinomyces, Alloprevotella, Capnocytophaga, Filifactor, Fretibacterium, Fusobacterium, Leptotrichia, Mogibacterium, Saccharibacteria [G-1], Selenomonas and Treponema. "Successfully treated" patients harboured higher proportions of Haemophilus, Rothia, and Lautropia and of Corynebacterium, Streptococcus and Peptidiphaga genera. Overall, patients with persistent generalized AgP (GAgP) revealed higher alpha diversity compared to persistent localized AgP (LAgP) and stable patients (p < .001). Beta diversity analyses revealed significant differences only between stable and persistent GAgP groups (p = .004). CONCLUSION: Patients with persistent AgP showed a more dysbiotic subgingival biofilm than those who have been successfully treated. It remains to be established whether such differences were predisposing to disease activity or were a result of a dysbiotic change associated with disease recurrence in the presence of sub-standard supportive periodontal therapy or other patient-related factors.

Decreased Consumption of Added Fructose Reduces Waist Circumference and Blood Glucose Concentration in Patients with Overweight and Obesity. The DISFRUTE Study: A Randomised Trial in Primary Care.

The relationship between fructose intake and insulin resistance remains controversial. Our purpose was to determine whether a reduction in dietary fructose is effective in decreasing insulin resistance (HOMA2-IR). This field trial was conducted on 438 adults with overweight and obese status, without diabetes. A total of 121 patients in a low fructose diet (LFD) group and 118 in a standard diet (SD) group completed the 24-week study. Both diets were prescribed with 30-40% of energy intake restriction. There were no between-group differences in HOMA2-IR. However, larger decreases were seen in the LFD group in waist circumference (-7.0 vs. -4.8 = -2.2 cms, 95% CI: -3.7, -0.7) and fasting blood glucose -0.25 vs. -0.11 = -0.14 mmol/L, 95% CI: -0.028, -0.02). The percentage of reduction in calorie intake was similar. Only were differences observed in the % energy intake for some nutrients: total fructose (-2 vs. -0.6 = -1.4, 95% CI: -2.6, -0.3), MUFA (-1.7 vs. -0.4 = -1.3, 95% CI: -2.4, -0.2), protein (5.1 vs. 3.6 = 1.4, 95% CI: 0.1, 2.7). The decrease in fructose consumption originated mainly from the reduction in added fructose (-2.8 vs. -1.9 = -0.9, 95% CI: -1.6, -0.03). These results were corroborated after multivariate adjustments. The low fructose diet did not reduce insulin resistance. However, it reduced waist circumference and fasting blood glucose concentration, which suggests a decrease in hepatic insulin resistance.

Proprotein convertase subtilisin/kexin type 9 in patients with systemic sclerosis.

OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation, and which has been linked to cardiovascular risk. The purpose of the present study was to examine whether PCSK9 serum levels are disrupted in patients with systemic sclerosis (SS) compared to controls, and if PCSK9 is related to disease-related data and the subclinical atherosclerosis that occurs in these patients. METHODS: Cross-sectional study that encompassed 146 individuals; 73 patients with SS and 73 age- and sex-matched controls. PCSK9, lipoproteins serum concentrations, and standard lipid profiles were assessed in patients and controls. Carotid intima-media thickness (cIMT) and the presence of carotid plaques were evaluated in SS patients. A multivariable analysis, adjusted for traditional cardiovascular risk factors, was performed to evaluate the differences in PCSK9 between patients and controls, the association of SS-related manifestations with PCSK9 levels, and if PCSK9 was associated with subclinical carotid atherosclerosis in SS patients. RESULTS: After multivariable analysis, PCSK9 was downregulated in SS patients compared to controls (beta coefficient -78 (95%CI -106 - -50) ng/ml, p=0.000) and skin thickness was associated with higher serum levels of PCSK9 (beta coef. 22 (7-37) units, p=0.005). PCSK9 was significantly and positively associated with cIMT (beta coef. 0.65 (0.06-1.24) ng/ml, p=0.031) in SS patients after multivariable adjustment. CONCLUSIONS: PCSK9 serum concentration is downregulated in SS patients compared to controls and is directly associated with disease severity subrogated parameters. PCSK9 was independently related to cIMT in SS patients.

Impaired HDL cholesterol efflux capacity in systemic lupus erythematosus patients is related to subclinical carotid atherosclerosis.

OBJECTIVES: Lipid profiles appear to be altered in SLE patients due to disease activity and inflammation. Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages. CEC has been linked to cardiovascular events in the general population and is impaired in SLE patients. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in SLE patients. METHODS: The present report is of a cross-sectional study that encompassed 418 individuals: 195 SLE patients and 223 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Carotid intima-media thickness and carotid plaques were evaluated in SLE patients. A multivariable analysis was performed to study the relationship of CEC to SLE-related data, lipid profile and subclinical carotid atherosclerosis. RESULTS: CEC was downregulated in SLE patients [8.1 (4.2) % vs 16.9 (10.4) %, P = 0.004). This occurred independently of traditional cardiovascular risk factors, statin use or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, and SLE-related data such as activity, severity or damage were not associated with CEC. After multivariable regression analysis including lipid profile-related molecules, CEC was inversely and independently associated with the presence of carotid plaques in SLE patients [odds ratio 0.87 (95% CI: 0.78, 0.97), P = 0.014]. CONCLUSION: CEC is impaired in SLE patients independently of other inflammation-related lipid profile modifications that occur during the disease. CEC is associated with carotid plaques in SLE patients.

Patients with suboptimal hepatitis B virus diagnostic characterization are at risk of liver fibrosis progression.

BACKGROUND: Many patients with chronic hepatitis B virus infection remain infradiagnosed and untreated. In a national health system with unrestricted access to treatment, our aims were to assess the level of compliance with clinical guidelines and the characteristics and risk of fibrosis progression in patients with suboptimal diagnosis. METHODS: In a cohort of patients with positive hepatitis B surface antigen from January 2011 to December 2013, data were registered to assess characteristics and compliance with guidelines. For assessing the risk of liver fibrosis, positive hepatitis B surface antigen patients from January 2008 to December 2013 were grouped depending on DNA request. Liver fibrosis was estimated by serological scores. RESULTS: Of 41 158 subjects with hepatitis B surface antigen request, 351 (0.9%) tested positive, and DNA was not available from 110 patients (66.4% male, mean 42.4 ± 14.5 years) after a median of 25.6 months (range 12.0-43.5). Most of these patients (76%) were assessed by primary care. Half of the patients (47.2%) showed hypertransaminasemia, at least significant fibrosis, or both conditions. After long follow-up (mean 90.1 ± 45.2 months), these patients had a higher risk of achieving at least significant fibrosis during follow-up (log-rank 8.73; P = 0.003). CONCLUSION: In more than one-third of patients with positive hepatitis B surface antigen, DNA was not requested despite showing hypertransaminasemia and significant fibrosis. Patients without DNA request are at high risk of liver fibrosis progression. Thus, educational measures and other strategies are necessary, especially targeting primary care, to improve access to treatment.

Risk of liver fibrosis progression in patients with suboptimal diagnosis of hepatitis C virus infection.

OBJECTIVE: Many hepatitis C virus (HCV)-infected patients have a suboptimal diagnosis. Particularly, the characteristics and risk of fibrosis progression of HCV antibody-positive patients without RNA testing are unknown. METHODS: Patients with a positive HCV antibody performed during 2005-2007 were classified based on RNA request and result until January 2017. Fibrosis was estimated with serologic scores. RESULTS: Of the 38 246 HCV tests performed, 791 (2.01%) patients tested positive. At the end of the follow-up (median 128.6 months, range 109.8-145.9), 49.43% (n = 391) of the subjects did not have RNA testing, 13.02% (n = 103) had undetectable RNA, and 37.55% (n = 297) had detectable RNA. After excluding patients without data for AST to platelet ratio index calculation (n = 334), patients without RNA testing (n = 122) compared with RNA undetectable (n = 92) were more frequently men (68.9 versus 46.7%), alcohol (52.6 versus 38.2%) and drug (53.0 versus 39.1%) users, lacking social support (50.4 versus 29.3%), and showed higher basal fibrosis. Patients without RNA testing had a significantly higher increase in the percentage of patients with ≥F2 (P = 0.035) and cirrhosis (P = 0.022). The relative risk for ≥F2 and cirrhosis in patients without RNA testing was 3.03 [95% confidence interval (CI): 1.54-5.98] and 4.31 (95% CI: 1.42-13.10), respectively. Non-RNA request was an independent predictor factor for progression to cirrhosis. CONCLUSION: In our cohort, patients with positive HCV antibody without RNA testing were more likely to be people at risk of social exclusion with an increased risk of fibrosis progression, because non-RNA request was a predictor for cirrhosis. Therefore, we urge support measures and strategies to link to care these difficult-to-treat populations.

Predictive factors for not undergoing RNA testing in patients found to have hepatitis C serology and impact of an automatic alert.

The process of diagnosis and linkage to care in cases of hepatitis C virus (HCV) infection remains an obstacle to disease control. The aims of this study were to evaluate predictive factors for not undergoing RNA testing among patients with positive HCV serology and impact of incorporating an automated electronic alert with recommendations in clinical practice. We collected HCV antibody tests requested from October 2011 to September 2014 to evaluate the rate of RNA testing and predictive factors for not undergoing RNA testing. Since October 2014, an automated alert notification has been implemented to remind physicians for testing RNA after a positive HCV test and referral to specialist care. 41 403 HCV antibody tests were requested from 34 073 patients. 870 (2.55%) patients tested positive. After a median of follow-up of 57.0 months (range 45.6-82.1), 37.6% did not have RNA testing. The independent predictors for not undergoing RNA testing were primary care serology requests (P < 0.001), no history of drug use (P = 0.005) and a lack of social support (P = 0.015). The intervention impact was evaluated in a pre-alert cohort (October 2011-September 2014) and a post-alert cohort (October 2014-September 2015). After the incorporation of the alert, the rate of RNA testing increased from 62.4% to 77.7% (P < 0.001). Incomplete assessment of HCV infection is a challenge in primary care. The implementation of an automated alert for recommending RNA testing after a positive HCV antibody test is feasible in clinical practice and increases the rate of patients with RNA testing.

Analysis of Availability and Access of Anti-myeloma Drugs and Impact on the Management of Multiple Myeloma in Latin American Countries.

INTRODUCTION: Latin American countries (LATAMC) represent a large fraction of patients treated for multiple myeloma (MM) worldwide. In order to understand the difficulty of access to anti-myeloma therapy in LATAMC, we designed this study that explores areas involved in the availability of drugs, such as health care systems, approval times, coverage of new agents, old drugs, use of generics, and the first-line treatments. MATERIAL AND METHODS: We collected data from 16 countries in 2015. RESULTS: The majority of LATAMC (88%; n = 14) had mixed public and private coverage, with patients with MM cared for in public institutions. Although bortezomib and lenalidomide were approved in 100% and 73% in LATAMC, these figures did not translate to real-world practice as one-half of the nations reported unequal access to the new agents (thalidomide, bortezomib, and lenalidomide) in both public and private systems. Conversely, cheaper old drugs, represented by melphalan, were not available commercially in 44% (n = 7) of nations. Thus, first-line MM treatments for old and young patients in public practice were triplets with thalidomide-alkylating agent-steroid, whereas in private practice, treatments involved bortezomib-alkylating agent-steroid. An alarming rate of 30% of the nations reported suboptimal regimens (eg, VAD [vincristine, adriamycin, and dexamethasone]) or the impossibility of transplantation. CONCLUSION: Our data indicates that bortezomib and transplant are still an unmet medical necessity in public systems. In the complex puzzle of myeloma drug access in LATAMC, important issues, such as the adjustment of disparities between health systems, the incorporation of new drugs with an economic cost-effectiveness view, and the re-establishment of essential old drugs, can be a platform to the future.

Disease Staging Index for Aggressive Periodontitis.

Major advances in the knowledge about the aetiopathogenesis of aggressive periodontitis (AgP) have been achieved. An ever increasing number of scientific articles related to AgP are published every year contributing significantly to the knowledge of this unique and complex disease. AgP has been classified into localised and generalised forms based on their extent and disease progression with distinct clinical and radiological features. A classification of AgP based on severity (mild, moderate and severe) exists; however, it is not easily applicable. Therefore, studies on AgP do not categorise the disease based on severity. A disease staging index for AgP is proposed based on clinical and radiological features, as well as risk factors. Based on the presence or absence of risk factors confirmed by longitudinal studies, cases of AgP can be divided into low risk, medium risk and high risk profiles for disease progression. Clinicians can devise a broad treatment plan for their AgP cases based on this staging. More frequent recall intervals are proposed for patients at medium and high risk for disease progression. Ten cases of AgP with 10-year follow-up were used to validate the staging index by retrospectively assigning prognosis and associating it with tooth loss. The use of this staging by researchers would increase external validity of research on AgP. Long-term analysis of AgP cases are needed to validate this staging index longitudinally.

Effectiveness of a low-fructose and/or low-sucrose diet in decreasing insulin resistance (DISFRUTE study): study protocol for a randomized controlled trial.

BACKGROUND: Research published to date on the relationship between insulin resistance (IR) and fructose consumption is scarce, has used different methods, and has yielded sometimes contradictory results. This study aims to determine whether a low-fructose and/or low-sucrose diet supervised by a physician or nurse decreases IR compared to a standard diet. METHODS/DESIGN: This field trial is located at primary care centers. The participants are adults aged 29 to 66 years, with a Body mass Index (BMI) between 29 and 40.99 kg/m2 and without diabetes. To date, 245 participants have been assigned randomly to the low-fructose diet intervention group (LFDI) at health centers in the western health service zone of Tenerife island, and 245 to the standard-diet control group (SDC) at health centers in the eastern health service zone. Recruitment is opportunistic and is carried out by physicians and nurses at participating health centers. Initially (baseline), and after 24 weeks of intervention, dietary records, physical activity, waist circumference, BMI, blood pressure, fasting blood glucose and insulin concentrations (HOMA2-IR) and lipid profile are recorded; blood glucose and insulin and lipid profile are also recorded 2 h after a 75-g glucose overload. After 48 weeks (24 weeks after the intervention), fasting blood samples are again obtained and a physical examination is performed. All tests and measures are repeated and recorded except dietary records, physical activity and oral glucose overload. Low-fructose diets are designed by calculating free and total (free + fructose associated with sucrose) fructose contents in standard diets, and removing foods with a fructose content in the highest quartile for the amounts in the standard diet. Participants in both groups are prescribed a diet that contains 30 to 40% less than the participant's energy requirements. The primary endpoint is change in HOMA2-IR between baseline and week 24, and other outcomes are change in HDL-cholesterol, LDL-cholesterol, triglycerides , waist circumference to height ratio and BMI. The secondary endpoint is change in HOMA2-IR between week 24 and week 48 together with the outcomes noted above. Comparisons between groups for variables used to indicate IR levels are done with a Student's t test for unpaired variables or the Mann-Whitney U test if the distribution is not normal. Multivariate regression models will be used to control for confounding factors not accounted for in the study design, and for independent prognostic factors. DISCUSSION: If the dietary intervention being tested, i.e., a diet low in fructose/sucrose, is able to reduce IR, the results - if translated into regular clinical practice - could provide a hitherto unavailable tool to prevent type-2 diabetes mellitus. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN41579277 . Registered retrospectively on 15 November 2016.