Association between periodontal condition and blood pressure is confounded by smoking.

OBJECTIVE: To investigate the role of smoking as a confounding factor in the association between periodontal pocketing and blood pressure. MATERIAL AND METHODS: After restriction to 45-64-year-old subjects without hypertension, diabetes, rheumatic diseases, obesity and with no history of cardiovascular diseases or ongoing lipid-lowering medications, the study population consisted of 307 subjects of the Health 2000 Survey in Finland. Systolic and diastolic blood pressure and pulse pressure (mmHg) were used as outcome variables. Periodontal condition was measured by the number of teeth with ≥4 mm periodontal pockets. ß-estimates and 95% confidence intervals (CI) were obtained from linear regression models. Analyses were made in the whole study population and stratified according to smoking habits/history. RESULTS: The number of teeth with ≥4 mm periodontal pockets associated statistically significantly with systolic blood pressure and pulse pressure in the whole study population. Among never-smokers or daily smokers, there were no consistent nor statistically significant associations between the number of teeth with ≥4 mm periodontal pockets and systolic/diastolic blood pressure or pulse pressure. CONCLUSIONS: Smoking appeared to confound the association between periodontal condition and blood pressure. Thorough control for the effect of smoking was not obtained using multivariate models.

Periodontal condition and ultrasound-based measures of arterial stiffness: results of the Health 2000 Survey.

BACKGROUND: Periodontitis has been associated with inflammatory processes in arterial walls such as impairment in endothelial function and thickening of intima media. As inflammation plays a role also in arterial stiffening, an association between periodontal inflammation and arterial stiffness can be expected. So far, conflicting results of the association between periodontal disease and arterial stiffness have been reported. Many of the earlier studies were conducted in specific populations and heterogeneous measures of both arterial stiffness and periodontal status were used. In this population-based study we aimed to investigate whether periodontal pocketing and gingival bleeding are associated with ultrasound-based measures of arterial stiffness. METHODS: In this cross-sectional study, two sets of data based on the national Health 2000 Survey in Finland were formed. Data set I comprised never-smoking 45-64-year-old dentate (≥ 10 natural teeth), non-diabetic, non-rheumatic, non-obese (BMI ≤ 30 kg/m2), non-hypertensive subjects with no coronary artery disease or ongoing lipid-lowering medications (n = 157). Data set II was formed of an unrestricted 45-74-year-old dentate population (n = 536). Four arterial stiffness measures (carotid artery compliance, Peterson's elastic modulus, Young's elastic modulus and beta stiffness index) based on an ultrasound examination of the common carotid artery were used. Periodontal parameters included the number of teeth with ≥ 4 mm deep periodontal pockets and the number of sextants with gingival bleeding. ß-estimates, confidence intervals, and p-values were obtained from linear regression models. RESULTS: In Data set I, the adjusted ß-estimates for the association between the number of teeth with ≥ 4 mm deep periodontal pockets and Peterson's elastic modulus and Young's elastic modulus were 15.80 (p = 0.12) and 61.02 (p = 0.22), respectively. The respective ß-estimates were 31.06 (p = 0.17) and 121.16 (p = 0.28) for the association between the number of bleeding sextants and these two stiffness measures. The results in Data set II were in line with the results in Data set I, with the exception that the adjusted ß-estimates for the associations between Peterson's elastic modulus and Young's elastic modulus and periodontal parameters were closer to null. CONCLUSIONS: This population-based study did not provide evidence of an association between periodontal condition and arterial stiffness.

Association of long-term obesity and weight gain with periodontal pocketing: Results of the Northern Finland Birth Cohort 1966 study.

AIM: To investigate whether obesity, central obesity, and weight gain are associated with periodontal pocketing. MATERIALS AND METHODS: A never-smoking sub-population (n = 725) of the Northern Finland Birth Cohort 1966 was categorized based on body mass index (BMI; participants with normal weight, overweight, and obesity) and waist circumference (WC; participants without central obesity and with central obesity) at ages 31 and 46. The categories were combined to define whether the participants stayed in the respective BMI and WC categories or moved on to a higher category during follow-up. A periodontal examination was done at age 46. RESULTS: WC was more consistently associated with periodontal pocketing than BMI. The relative risks for the number of sites with periodontal pocket depth (PPD) ≥4 mm and bleeding PPD ≥4 mm in participants with central obesity both at age 31 and at age 46 were 1.7 (95% confidence interval [CI] 1.4-2.0) and 2.1 (95% CI 1.6-2.6). The corresponding values for participants who had no central obesity at age 31 but had central obesity at age 46 were 1.6 (95% CI 1.4-1.8) and 1.9 (95% CI 1.6-2.3). CONCLUSION: Of all the studied measures, central obesity appeared to be most strongly associated with the inflammatory condition of the periodontium.

Association of hyperglycaemia with periodontal status: Results of the Northern Finland Birth Cohort 1966 study.

AIM: To investigate the association of hyperglycaemia and changes in glycaemic control with periodontal status in non-diabetic individuals. MATERIALS AND METHODS: A sub-population (n = 647) of the Northern Finland Birth Cohort 1966 was studied. We categorized long-term glucose balance based on fasting plasma glucose (FPG) at ages 31 and 46: FPG <5.0 mmol/l (strict normoglycaemia), FPG 5.0-5.59 mmol/l (slightly elevated FPG) and FPG 5.6-6.9 mmol/l (prediabetes). Probing pocket depth (PPD) and alveolar bone level (BL) data were collected at age 46. Relative risks (RR, 95% CI) were estimated using Poisson regression models. RESULTS: Periodontal status was poorer in individuals whose glucose balance worsened from age 31 to 46 years than in those with a stable glucose balance. In the case of strict normoglycaemia at age 31 and slightly elevated FPG or prediabetes at age 46, the RRs for PPD ≥4 mm were 1.8 (95% CI 1.4-2.2) and 2.8 (95% CI 2.0-3.8) and for BL ≥5 mm 1.1 (95% CI 0.8-1.4) and 1.8 (95% CI 1.2-2.8), respectively. CONCLUSION: The results of this population-based cohort study suggest that impairment in glucose control in non-diabetic individuals is associated with periodontal pocketing and alveolar bone loss.

Genome-wide association study of periodontal pocketing in Finnish adults.

BACKGROUND: A genome-wide association study is an analytical approach that investigates whether genetic variants across the whole genome contribute to disease progression. The aim of this study was to investigate genome-wide associations of periodontal condition measured as deepened periodontal pockets (≥ 4 mm) in Finnish adults. METHODS: This study was based on the data of the national Health 2000 Survey (BRIF8901) in Finland and the Northern Finland Birth Cohort 1966 Study totalling 3,245 individuals. The genotype data were analyzed using the SNPTEST v.2.4.1. The number of teeth with deepened periodontal pockets (≥ 4 mm deep) was employed as a continuous response variable in additive regression analyses performed separately for the two studies and the results were combined in a meta-analysis applying a fixed effects model. RESULTS: Genome-wide significant associations with the number of teeth with ≥ 4 mm deep pockets were not found at the p-level of < 5 × 10-8, while in total 17 loci reached the p-level of 5 × 10-6. Of the top hits, SNP rs4444613 in chromosome 20 showed the strongest association (p = 1.35 × 10-7). CONCLUSION: No statistically significant genome-wide associations with deepened periodontal pockets were found in this study.

Long-term metabolic syndrome is associated with periodontal pockets and alveolar bone loss.

AIM: To investigate whether the metabolic syndrome (MetS) is associated with deepened periodontal pockets and alveolar bone loss. MATERIALS AND METHODS: This study was based on a subpopulation of the Northern Finland Birth Cohort 1966 survey (n = 1964). The criteria of the AHA/NHLBI were used to determine MetS. The analyses were based on the metabolic data at ages 31 and 46, and probing pocket depth and alveolar bone level data at age 46. Relative risks (RR, 95% CI) were estimated using Poisson regression models. RESULTS: Relative risks for PD ≥ 4 mm and BL ≥ 5 mm were higher in individuals with an exposure to MetS ≥ 15 years (RR 1.8, 95% CI 1.6-2.1 and RR 1.5, 95% CI 1.3-1.9, respectively) than in those whose exposure was <15 years (RR 1.2, 95% CI 1.1-1.3 and RR 1.1, 95% CI 1.0-1.3, respectively). Consistently stronger associations were found in never smokers. Women showed stronger associations of MetS with PD ≥ 4 mm than men. The association with BL ≥ 5 mm was observed only in men. CONCLUSION: A long-term exposure by MetS was associated independently and in an exposure-dependent manner with periodontal pockets and alveolar bone level.

Serum parathyroid hormone and active vitamin D in chronic periodontitis.

OBJECTIVES: To study the association between periodontitis and serum parathyroid hormone (PTH) and the response of PTH to periodontal therapy in type 1 diabetic patients (T1DM). We also investigated the PTH-1,25(OH)2 D axis in the T1DM group. METHODS: Periodontal health status was recorded in 54 periodontitis patients and 30 periodontally healthy controls (case-control data). Data were also collected from patients with type 1 diabetes mellitus at the baseline (n = 76) and after periodontal therapy (intervention data) (n = 53). RESULTS: Periodontitis was not associated with serum PTH in the case-control data or at the baseline of the intervention data. A post-therapy increase in serum PTH was found in 61% of the T1DM patients; in patients with moderate or severe periodontitis (n = 26) the average increase was 0.6 pmol/l (p = 0.016) and in patients with no or mild periodontitis (n = 27) 0.2 pmol/l (p = 0.250). In 47% of the T1DM patients, an increase in PTH was associated with an increase in serum 1,25(OH)2 D. CONCLUSION: An association between serum PTH and periodontal infection was found only after periodontal therapy in T1DM patients. This post-treatment response in serum PTH may partly explain the previously reported increase in serum 1,25(OH)2 D.

Association between periodontal condition and hypertension in a non-smoking population aged 30-49 years: results of the Health 2000 Survey in Finland.

AIM: The aim of this cross-sectional study was to investigate whether periodontal condition is associated with hypertension and systolic blood pressure. MATERIALS AND METHODS: The study population consisted of dentate, non-diabetic, non-smoking individuals aged 30-49 years (n = 1296) in the national Health 2000 Survey in Finland. The number of teeth with deepened (≥4 mm) and deep (≥6 mm) periodontal pockets and the number of sextants with gingival bleeding were used as explanatory variables. Hypertension and systolic blood pressure were used as outcome variables. RESULTS: There was no consistent association between the number of teeth with deepened (≥4 mm) (OR 0.98, 95% CI 0.95-1.01) or deep (≥6 mm) (OR 1.01, 95% CI 0.90-1.12) periodontal pockets and hypertension after adjusting for confounding factors. Nor was there any essential association between the number of bleeding sextants and hypertension. CONCLUSIONS: Periodontal pocketing and gingival bleeding did not appear to be related to hypertension in non-diabetic, non-smoking individuals aged 30-49 years. Further studies using experimental study designs would be required to determine the role of infectious periodontal diseases in the development or progression of hypertension.

Role of insulin sensitivity and beta cell function in the development of periodontal disease in adults without diabetes.

AIM: The goal of this study was to explore whether insulin resistance and beta cell function are related to periodontal pocket formation, indicative of infectious periodontal disease in non-smoking adults without manifest diabetes. MATERIAL AND METHODS: We analysed data from a Health 2000 Survey consisting of dentate subjects without any indication of diabetes, aged between 30 and 64, who had never smoked and who had participated in the Follow-up Study on Finnish Adults' Oral Health about 4 years later (n = 157). The Homeostasis Model Assessment Indices were used to measure insulin resistance (HOMA-IR) and ß-cell function (HOMA-B). The development of periodontal disease was measured by means of the incidence of deepened periodontal pockets (4 mm deep or deeper) during the follow-up period. Incidence rate ratios (IRR) were estimated using Poisson regression models. RESULTS: Both HOMA-IR and HOMA-B indices were associated with periodontal pocket formation during the 4-year follow-up. CONCLUSION: The results of this follow-up study suggest that impaired glucose metabolism measured as insulin resistance and altered beta cell function predict the breakdown of periodontal tissues. Further studies about their role in the pathogenesis of periodontal diseases are needed.

Serum osteoprotegerin and periodontal destruction in subjects with type 1 diabetes mellitus.

AIM: Besides their role in bone metabolism, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are also known to be associated with inflammation. We explored associations between the extent/severity of periodontitis and circulating levels of sRANKL and OPG and their ratio using a cross-sectional study design. SUBJECTS & METHODS: The extent of periodontal inflammation and tissue destruction and the serum levels of sRANKL (pg/ml) and OPG (pg/ml) were determined in 80 subjects with type 1 diabetes mellitus (T1DM). Plaque-, age-, gender-, smoking-, HbA1c- and body mass index-adjusted associations between periodontal parameters and serum sRANKL, OPG and their ratio were studied using multiple linear regression analysis. RESULTS: Adjusted regression analyses of all the subjects indicated a significant positive association between AL ≥ 4 mm and severity of periodontitis and the level of serum OPG. A major drop in the strength and statistical significance of the above association was observed when the analyses included only non-smokers. Serum sRANKL level and sRANKL/OPG ratio were not associated with periodontitis. CONCLUSION: Our observations suggest that serum OPG may be an indicator of periodontal tissue destruction in T1DM.

Serum lipids modify periodontal infection - C-reactive protein association.

AIM: To investigate whether low-grade inflammation-related factors such as serum low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C) modify the association between periodontal infection and C-reactive protein. MATERIAL AND METHODS: This study was based on a subpopulation of the Health 2000 Survey, which consisted of dentate, non-diabetic, non-rheumatic subjects who were 30-49 years old (n = 2710). The extent of periodontal infection was measured by means of the number of teeth with periodontal pocket ≥4 mm and teeth with periodontal pocket ≥6 mm and systemic inflammation using high sensitive C-reactive protein. RESULTS: The extent of periodontal infection was associated with elevated levels of C-reactive protein among those subjects whose HDL-C value was below the median value of 1.3 mmol/l or LDL-C above the median value of 3.4 mmol/l. Among those with HDL-C ≥ 1.3 mmol/l or LDL-C ≤ 3.4 mmol/l, the association between periodontal infection and serum concentrations of C-reactive protein was practically non-existent. CONCLUSION: This study suggests that the relation of periodontal infection to the systemic inflammatory condition is more complicated than previously presumed. The findings of this study suggest that the possible systemic effect of periodontal infection is dependent on serum lipid composition.

Serum high-density lipoprotein cholesterol level associated with the extent of periodontal inflammation in type 1 diabetic subjects.

AIM: High-density lipoprotein (HDL) cholesterol is known for its anti-inflammatory and antioxidant activities in protection against cardiovascular diseases. We investigated whether a protective association also exists between serum HDL and periodontal inflammation in type 1 diabetic subjects (T1DM). METHODS: Plaque and periodontal inflammation (bleeding and PD ≥ 4 mm) were examined in 80 subjects with T1DM. The serum levels of glycosylated haemoglobin (HbA1c, %) and HDL (mmol/l) were determined. Adjusted associations between inflammation and serum HDL were analysed using linear regression analysis. To study the linearity of the association, the subjects were categorized into HDL tertiles (I-III). RESULTS: A statistically significant negative association was observed between serum HDL level and the extent of bleeding and PD ≥ 4 mm. Subjects in HDL tertiles II and III (high HDL) presented significantly fewer inflamed sites when compared with the subjects in tertile I (low HDL), whereas no significant difference in the number of inflamed sites was observed between tertiles II and III. CONCLUSIONS: Based on the finding of a negative association between serum HDL and periodontal inflammation, HDL may be considered a marker of susceptibility to periodontal inflammation. A longitudinal study is needed to verify possible causal relationship between serum HDL and inflammation.

Serum interleukin-6 may modulate periodontal inflammation in type 1 diabetic subjects.

AIMS: To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators. MATERIAL AND METHODS: Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models. RESULTS: The level of serum IL-6 was associated with the extent of bleeding and PD≥4 mm at the baseline in non-smokers and in subjects with BMI≤26 kg/m(2). These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level. CONCLUSIONS: The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

Serum levels of interleukin-10 and tumour necrosis factor-α in chronic periodontitis.

AIMS: To investigate, using a cross-sectional study design, whether the extent of periodontal inflammation associates with the serum levels of cytokine interleukin (IL)-10 and tumour necrosis factor (TNF)-α and their ratio. MATERIAL AND METHODS: The study group consisted of 61 subjects with chronic periodontitis and 30 control subjects with minimally inflamed periodontal tissues. Probing pocket depth (PD), bleeding on probing (BOP) and periodontal attachment level (AL) were measured. The serum IL-10 (pg/ml) and TNF-α (U/l) levels were analysed using enzyme-linked immunosorbent assays. After categorization of the subjects, associations between serum IL-10 and TNF-α levels and the extent of periodontal inflammation were studied using linear regression models adjusted for age, gender, body mass index and smoking. RESULTS: A negative, partly dose-dependent association existed between the extent of BOP, PD ≥ 4 mm and AL ≥ 4 mm and serum IL-10 level. The subjects in the periodontitis group presented significantly higher serum TNF-α levels and their TNF-α/IL-10 ratio was approximately threefold when compared with the ratio in the control group. CONCLUSIONS: The significantly higher serum TNF-α/IL-10 ratio in the subjects with chronic periodontitis when compared with the ratio in the controls is indicative of a stronger systemic pro-inflammatory state in chronic periodontitis.

Resolution of periodontal inflammation does not guarantee improved glycemic control in type 1 diabetic subjects.

OBJECTIVE: The aim of this study was to find out if periodontal therapy has any effect on glycemic control of type 1 diabetes mellitus (DM). SUBJECTS AND METHODS: The periodontal health status of 65 type 1 diabetic subjects was assessed at the baseline and 8 weeks after completion of periodontal therapy. Glycemic control was assessed on both visits by measuring the percentage of glycosylated haemoglobin (GHbA1c). The change in HbA1c (DeltaHbA1c) was assessed by using both a positive or negative change >or=0.5% and any change in HbA1c. RESULTS: The mean HbA1c level (+/-SD) of the whole study group was 8.6% (+/-1.5) at the baseline and 8.5% (+/-1.5) after treatment. Glycemic control improved during the study period in 23 subjects (35%) and worsened in 18 subjects (28%). Approximately 78% of the bleeding sites and 87% of the sites with probing depth >or=4 mm presented healing. DeltaHbA1c associated significantly with baseline HbA1c but not with baseline periodontal health status or periodontal healing. CONCLUSION: Regardless of a significant resolution of periodontal infection, a great majority of the subjects did not present any improvement in their glycemic control.

IL-6(-174) genotype associated with the extent of periodontal disease in type 1 diabetic subjects.

AIM: The aim of this study was to investigate whether genetic polymorphism in certain cytokine and receptor molecule genes and diabetic status associate with the extent of periodontal disease in type 1 diabetes mellitus (DM). MATERIAL AND METHODS: Eighty patients with type 1 DM participated. Visible plaque, bleeding on probing (BOP), probing pocket depth (PD) and attachment level (AL) were examined clinically and glycosylated haemoglobin (HbA1c) levels were used to assess the glycemic control of DM. CD-14, IL-6, TNF-alpha, IL-10, IL-1alpha, IL-1beta and TLR-4 gene polymorphisms were studied using the polymerase chain reaction (PCR). RESULTS: The 3-year HbA1c was good (<7.5%) in 16%, acceptable (7.5-8.5%) in 36% and poor (>8.5%) in 48% of the subjects. IL-6(-174) genotype and 3-year GHbA1c associated significantly with BOP and PD>or=4 mm, subjects with the GG genotype of the IL-6(-174) exhibiting more severe periodontal disease than those with the GC/CC genotype. After stratification by IL-6 genotype, associations between the extent of periodontal disease and 3-year HbA1c levels remained significant in subjects carrying the GC/CC but not the GG genotype. CONCLUSIONS: In addition to the HbA1c level, the IL-6(-174) genotype is a significant susceptibility factor for periodontal disease among type 1 diabetics.

Matrix metalloproteinase-8 concentration in shallow crevices associated with the extent of periodontal disease.

OBJECTIVE: The aim of this study was to analyse the association between matrix metalloproteinase-8 (MMP-8) concentration in shallow, mostly non-bleeding gingival crevices, and the extent of periodontal disease. MATERIAL AND METHODS: Plaque, bleeding on probing (BOP), probing pocket depth (PPD) and attachment level (AL) were assessed clinically in 48 patients with chronic periodontitis. MMP-8 concentrations in gingival crevicular fluid (GCF) from four shallow (PPDor=4 mm (p=0.028) and AL>or=6 mm (p<0.001). CONCLUSION: The above association between MMP-8 concentration in shallow crevices and attachment loss provides a new aspect to future studies of MMP-8 as a prognostic marker for periodontal disease.

Diagnosis and Treatment of Orofacial Granulomatosis.

Orofacial granulomatosis (OFG) is a chronic inflammatory disorder characterized by lip swelling and gingival alterations. OFG occurs either as a separate clinical entity or associated with a systemic disorder such as Crohn's disease (CD). The purpose of this paper is to report the case of a 13-year old boy who presented with marked granulomatous gingival inflammation and stomach discomfort. Periodontal therapy resulted in only slight reduction in gingival inflammation and enlargement. The diagnosis of OFG, which was evidently associated with inflammation in the bowel, was based on the gingival status and biopsy, self-reported symptoms, and laboratory markers of iron metabolism and fecal calprotectin level. The gingival and bowel inflammation was controlled with, strict adherence to a cinnamon- and benzoate-free diet combined with periodontal prophylaxis. At this point at the age of 17 years, the patient has avoided the use of immune modulatory treatments.

The Efficacy of Supportive Peri-Implant Therapies in Preventing Peri-Implantitis and Implant Loss: a Systematic Review of the Literature.

OBJECTIVES: To study the efficacy of supportive peri-implant therapies in preventing clinical and radiological signs of peri-implantitis and implant loss. MATERIAL AND METHODS: Longitudinal human studies, published between January 1, 2006, and February 1, 2016, were included based on an electronic search using MEDLINE and EMBASE databases and complemented by a manual search. Articles were included only if 1) they comprised a group of patients involved in/adhering to regular supportive peri-implant therapies (SPTs) and a control group without such therapies or with poor adherence to them, 2) the protocol of the SPTs was clearly described and 3) the outcome was indicated by means of clinical/radiological changes or implant loss. RESULTS: After initially identifying a total of 710 titles and abstracts, 12 full text articles were selected for eligibility assessment. Seven studies, three prospective and four retrospective, fulfilled the inclusion criteria for this review. The frequency of recall visits varied between the studies from a minimum of one visit every three months to an individually tailored regimen. In all the studies a lack of SPTs or poor adherence to them resulted in significantly higher frequencies of sites with mucosal bleeding, deepened peri-implant pockets or alveolar bone loss. In line with the above, a lack of/poor adherence to SPTs was associated with higher implant loss. CONCLUSIONS: To prevent peri-implantitis, an individually tailored supportive programme based on patient motivation and re-instruction in oral hygiene measures combined with professional implant cleaning seem to be crucial.

The 1st Baltic Osseointegration Academy and Lithuanian University of Health Sciences Consensus Conference 2016. Summary and Consensus Statements: Group III - Peri-Implantitis Treatment.

INTRODUCTION: The task of Group 3 was to review and update the existing data concerning non-surgical, surgical non-regenerative and surgical regenerative treatment of peri-implantitis. Special interest was paid to the preventive and supporting therapy in case of peri-implantitis. MATERIAL AND METHODS: The main areas of interest were as follows: effect of smoking and history of periodontitis, prosthetic treatment mistakes, excess cement, overloading, general diseases influence on peri-implantitis development. The systematic review and/or meta-analysis were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. The literature in the corresponding areas of interest was searched and reported using the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. The method of preparation of systematic reviews of the literature based on comprehensive search strategies was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic review and/or meta-analysis is presented in Preface chapter. RESULTS: The results and conclusions of the review process are presented in the respective papers. The group's general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article.