Rastreio de câncer na prática clínica: recomendações para a população de risco habitual / Cancer screening in clinical practice: recommendations for average risk population

Objetivo: Compilar as evidências da literatura e as recomendações das principais sociedades médicas mundiais para o rastreamento populacional de câncer, contextualizando com a relevância epidemiológica de cada subtipo da doença. Métodos: Trata-se de revisão narrativa da literatura, realizada por levantamento na base de dados PubMed® e consulta aos posicionamentos de instituições governamentais e sociedades médicas nas áreas específicas. Resultados: O rastreamento populacional sistemático foi recomendado apenas para as neoplasias de mama, colo do útero e colorretal, utilizando-se métodos, idade e periodicidade específicos. O rastreio do câncer de próstata mostrou-se controverso, e o pulmonar e o hepático recomendados apenas em tabagistas com alta carga tabágica e cirróticos, respectivamente. Não houve evidência para se recomendar atualmente o rastreamento sistemático da população geral para as neoplasias de pele, tireoide, esôfago, estômago, pâncreas, ovário, endométrio, bexiga, rins, dentre outras. Conclusão: O exame periódico de saúde do paciente saudável abrangeu a prevenção e o rastreamento do câncer para redução de morbidade e mortalidade pela doença, e a estratificação das evidências atuais teve o potencial de melhorar o direcionamento dos esforços, aumentando a cobertura, havendo maior benefício e reduzindo riscos e custos de exames desnecessários.

Objective: To gather evidence from the literature, and recommendations of the main medical societies worldwide for the population screening of cancer, contextualizing with the epidemiological relevance of each subtype of the disease. Methods: This is a narrative review of the literature, carried out through research on PubMed® database, and consultation to the governmental institutions and medical societies' opinions in specific areas. Results: Systematic population screening was recommended only for breast, cervix and colorectal cancers, using specific methods, age and periodicity. Prostate cancer screening showed to be controversial, and pulmonary and hepatic screening are recommended only in heavy smokers and cirrhotic patients, respectively. Currently, there is no evidence to recommend the screening of the general population for neoplasms of skin, thyroid, esophagus, stomach, pancreas, ovary, endometrium, bladder, and kidneys. Conclusion: The periodic health screening of the healthy patient covered the prevention and screening for cancer to reduce morbidity and mortality from the disease; the stratification of current evidence has the potential to improve the direction of efforts, broadening coverage, with more benefit, and reducing risks and costs of unnecessary tests.

Stress management in obesity during a thermal spa residential programme (ObesiStress): protocol for a randomised controlled trial study.

INTRODUCTION: Stress and obesity are two public health issues. The relationship between obesity and stress is biological through the actions of stress on the major hormones that regulate appetite (leptin and ghrelin). Many spa resorts in France specialise in the treatment of obesity, but no thermal spa currently proposes a specific programme to manage stress in obesity. The ObesiStress protocol has been designed to offer a new residential stress management programme. This thermal spa treatment of obesity implements stress management strategies as suggested by international recommendations. METHODS AND ANALYSIS: 140 overweight or obese participants with a Body Mass Index of >25 kg/m2 and aged over 18 years will be recruited. Participants will be randomised into two groups: a control group of usual practice (restrictive diet, physical activity and thermal spa treatment) and an intervention group with stress management in addition to the usual practice. In the present protocol, parameters will be measured on five occasions (at inclusion, at the beginning of the spa (day 0), at the end of the spa (day 21), and at 6 and 12 months). The study will assess the participants' heart rate variability, cardiac remodelling and function, electrodermal activity, blood markers, anthropometric profile, body composition, psychology and quality of life via the use of questionnaires and bone parameters. ETHICS AND DISSEMINATION: The ObesiStress protocol complies with the ethics guidelines for Clinical Research and has been approved by the ethics committee (CPP Sud-Est VI, Clermont-Ferrand - ANSM: 2016-A01774-47). This study aimed to highlight the efficacy of a 21-day thermal spa residential programme of stress management in obesity through objective measurements of well-being and cardiovascular morbidity. Results will be disseminated during several research conferences and articles published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03578757.

SPAR - a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial.

BACKGROUND: Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG). METHODS: A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1-2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4-5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018. DISCUSSION: When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations. TRIAL REGISTRATION: ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).

Prediction and clinical utility of a contralateral breast cancer risk model.

BACKGROUND: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. METHODS: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. RESULTS: In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS: We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.

Effectiveness and cost-effectiveness of Improving clinicians' diagnostic and communication Skills on Antibiotic prescribing Appropriateness in patients with acute Cough in primary care in CATalonia (the ISAAC-CAT study): study protocol for a cluster randomised controlled trial.

BACKGROUND: Despite their marginal benefit, about 60% of acute lower respiratory tract infections (ALRTIs) are currently treated with antibiotics in Catalonia. This study aims to evaluate the effectiveness and efficiency of a continuous disease-focused intervention (C-reactive protein [CRP]) and an illness-focused intervention (enhancement of communication skills to optimise doctor-patient consultations) on antibiotic prescribing in patients with ALRTIs in Catalan primary care centres. METHODS/DESIGN: A cluster randomised, factorial, controlled trial aimed at including 20 primary care centres (N = 2940 patients) with patients older than 18 years of age presenting for a first consultation with an ALRTI will be included in the study. Primary care centres will be identified on the basis of socioeconomic data and antibiotic consumption. Centres will be randomly assigned according to hierarchical clustering to any of four trial arms: usual care, CRP testing, enhanced communication skills backed up with patient leaflets, or combined interventions. A cost-effectiveness and cost-utility analysis will be performed from the societal and national healthcare system perspectives, and the time horizon of the analysis will be 1 year. Two qualitative studies (pre- and post-clinical trial) aimed to identify the expectations and concerns of patients with ALRTIs and the barriers and facilitators of each intervention arm will be run. Family doctors and nurses assigned to the interventions will participate in a 2-h training workshop before the inception of the trial and will receive a monthly intervention-tailored training module during the year of the trial period. Primary outcomes will be antibiotic use within the first 6 weeks, duration of moderate to severe cough, and the quality-adjusted life-years. Secondary outcomes will be duration of illness and severity of cough measured using a symptom diary, healthcare re-consultations, hospital admissions, and complications. Healthcare costs will be considered and expressed in 2021 euros (year foreseen to finalise the study) of the current year of the analysis. Univariate and multivariate sensitivity analyses will be carried out. DISCUSSION: The ISAAC-CAT project will contribute to evaluate the effectiveness and efficiency of different strategies for more appropriate antibiotic prescribing that are currently out of the scope of the actual clinical guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03931577.

Comparison of the effects of low-level laser and pulsed and continuous ultrasound on pain and physical disability in chronic non-specific low back pain: a randomized controlled clinical trial.

OBJECTIVE: To compare the short-term effects of pulsed laser and pulsed and continuous ultrasound on pain and functional disability in women with chronic non-specific low back pain. METHODS: The sample was composed of 100 volunteers randomly allocated into four groups: The Pulsed Laser Group (n = 26) was treated with 3 J/cm2; the Pulsed Ultrasound Group (n = 24; 3 MHz) was treated with 1 W/cm2; the Continuous Ultrasound Group (n = 26; 1 MHz) was treated with 1 W/cm2; and a Control Group (n = 24), where the patients were still waiting for treatment. Before and after 10 sessions of treatment, the intensity of pain was assessed using the visual analogue scale (VAS), the quality of pain was evaluated using the McGill pain questionnaire and functional disability was investigated using the Roland-Morris questionnaire. RESULTS: The three treated groups exhibited a decrease in pain (p < 0.001); the Pulsed Laser Group showed the greater relative gain (91.2%), Meanwhile, the Control Group exhibited a worsening of - 5.8%. The three treated groups demonstrated improvement in the quality of pain (McGill) in the total, sensory and affective dimensions (p < 0.005; p < 0.002; p < 0.013, respectively). All treated groups showed a decrease in functional disability (p < 0.001), but the Pulsed Ultrasound Group showed the highest relative gain (83.3%). CONCLUSIONS: The three modalities have significant effects to decreasing low back pain and improving functional disability in women with non-specific chronic low back pain, but the pulsed low-level laser had the best results on pain while the pulsed ultrasound had the best results on improve the functional disability. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02150096.

Effectiveness of two bundles in venous leg ulcer healing: A randomized controlled trial.

The objective of this study was to compare the effectiveness of 2 bundles in venous leg ulcer healing. This study is a open, randomized, controlled clinical trial with parallel treatment, 1:1 allocation rate, and 24-week follow-up. Twenty-eight patients with venous leg ulcers of the lower limbs were allocated to 2 groups: group A (n = 14) and group B (n = 14). The mean age of the participants was 59.67 ± 11.95 years, and the mean ulcer surface area was 29.32 (±98.43) cm2. The primary outcome was ulcer healing. Secondary outcomes were wound area reduction rate, Pressure Ulcer Scale of Healing (PUSH) scores, and the presence and intensity of pain before, during and after dressing change. Two different bundles were applied in 2 phases to the randomized groups. All participants engaged in an educational activity, performed exercises, rested with legs elevated, received oral nutrition supplementation (Cubitan; Danone Nutricia), and had their ulcers cleaned with warm saline solution and biguanide polyhexanide solution (Prontosan; B. Braun). Topical therapy in the first phase was papain 2% or 4% for group A and 2% hydrogel for group B. Both groups received single-layer elastic compression therapy (SurePress; ConvaTec). In the second phase, group A received compression therapy with Unna boot (Viscopaste; Smith-Nephew) as the primary dressing, while group B received a cellulose membrane (Membracel; Vuelo Pharma) followed by the Unna boot (Viscopaste; Smith-Nephew).In group A, 71.42% of the ulcers healed; in group B, the figure was 64.28%. Wound area, PUSH scores, and the occurrence and intensity of pain decreased significantly and equivalently in groups A and B.Both bundles are effective in the treatment of venous leg ulcers and pain relief.

The effect of the blended education program on treatment concordance of patients with hypertension: A single-blind randomized, controlled trial.

Poor treatment concordance is one of the major problems in patients with hypertension (HTN). An appropriate teaching method can help solving this problem. This study aimed to determine the effect of blended education program on treatment concordance in patients with HTN. This is a single-blind randomized controlled trial, and 60 patients with HTN who met inclusion criteria were selected by a convenience sampling and allocated into the control and intervention groups. A demographic information form and the questionnaires were used in this study. The questionnaires included questions addressing treatment concordance, which explored three dimensions: dietary adherence, medication adherence, physical activity plan. The blended educational intervention was carried out for 4 weeks in the intervention group. The control group only received traditional face-to-face education. The results showed that there was a significant increase in the total score of treatment concordance of the intervention group compared to the control group after the intervention (P < .001). In conclusion, using a blended education program is highly recommended to improve treatment concordance in patients with HTN. Consequently, it reduces patients' medical costs and enhances their health-related quality of life.

Randomised controlled trial to evaluate the influence of mHealth and eHealth skin cancer prevention education among young organ transplant recipients: the HIPPOlino intervention study.

OBJECTIVES: To determine whether a multicomponent sun protection intervention programme (mHealth) for young organ transplant recipients (OTR) leads to a higher increase of preventive knowledge and behavioural change than an e-learning education programme (eHealth). DESIGN: Randomised controlled trial with one preintervention baseline survey and three follow-up surveys after 6 weeks, 6 and 12 months. Comparison of two different intervention schedules with a control group (CG). SETTING: Multicomponent sun protection trainings in Germany, the Netherlands and Austria between June 2013 and September 2015. PARTICIPANTS: 137 OTRs (5-22 years of age, 61 females/76 males) participated in the study. INTERVENTIONS: (A) Intervention group 1 (IG1): personal training with subsequent forwarding of individual ultraviolet index-dependent sun protection recommendations via short message service (SMS); (B) intervention group 2 (IG2): e-learning training without SMS; (C) CG: regular information letters, online training after 1 year. OUTCOME MEASURES: Key questions were used to form a knowledge and a behavioural score. Behavioural strategies and knowledge were quantified through self-administered questionnaires. RESULTS: Analyses 6 weeks after the intervention showed a higher knowledge increase in both IG compared with the CG (IG1 to CG: OR 12.64, 95% CI 4.20 to 38.20; IG2 to CG: OR 2.59, 95% CI 0.95 to 7.04). Sun protection behaviour improved slightly but not significantly in both IG (IG1 to CG: OR 2.56, 95% CI 0.93 to 7.00; IG2 to CG: OR 1.22, 95% CI 0.45 to 3.32). One year after the intervention, no behavioural changes were observed in either IG compared with the CG. IG1 but not IG2 still scored significantly higher in sun protection knowledge than the CG 1 year after intervention (IG1 to CG: OR 4.46, 95% CI 1.48 to 13.43; IG2 to CG: OR 1.41, 95% CI 0.51 to 3.93). CONCLUSIONS: This multicomponent sun protection programme provides a promising strategy to increase sun protection knowledge and possibly also protective behaviour in young OTR. TRIAL REGISTRATION NUMBER: DRKS00011393.

Obstacle avoidance training for individuals with stroke: a systematic review and meta-analysis.

OBJECTIVES: To accumulate evidence that obstacle avoidance training alone is effective in improving the locomotor ability of individuals with stroke. DESIGN: Systematic review and meta-analysis. SETTING: MEDLINE, EMBASE, CENTRAL, ICTRP and PEDro were searched for related information until December 2018. Two independent reviewers extracted data. Outcome measurement data were subjected to meta-analyses using random-effects models. Data syntheses were conducted using RevMan V.5.3, and the certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach. PARTICIPANTS: Participants with various types and phases of stroke were included. INTERVENTION: The usual gait training including obstacle avoidance training (interventions of any type, intensity, duration and frequency). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were gait speed, composite gait ability and objective balance ability. Secondary outcomes were subjective balance ability, gait endurance and fall incidence. RESULTS: Two randomised controlled trials with a total of 49 participants were used as data sources for this study. The obstacle avoidance training (training) group had lower gait speed than the control group (mean difference (MD) 0.03, 95% CI -0.11 to 0.16, p=0.51). Further, the certainty of evidence was very low. The subjective balance ability (Activities-specific Balance Confidence scale) was not significantly different between the training and control groups (MD 6.65, 95% CI -7.59 to 20.89, p=0.36), and it showed very low certainty of evidence. CONCLUSIONS: Obstacle avoidance training may have little or no effect on individuals with stroke. The failure to find the effectiveness of obstacle avoidance training alone is possibly attributable to the insufficient amount of training in the intervention and the lack of well-designed studies that measured relevant outcomes. PROSPERO REGISTRATION NUMBER: CRD42017060691.

Lower risk of smoking-related cancer in individuals with familial hypercholesterolemia compared with controls: a prospective matched cohort study.

According to guidelines, individuals with familial hypercholesterolemia (FH) shall receive lifestyle intervention and intensive lipid-lowering treatment from early in life to reduce the risk of coronary heart disease. Our aim was to study if treatment of FH also could affect risk of lifestyle-related cancer. We presented cumulative incidence of total cancer and lifestyle-related cancer sites in individuals with genetically verified FH (n = 5531) compared with age and sex matched controls (n = 108354). Individuals with FH had 20% lower risk of smoking-related cancer compared with the control population [HR 0.80 (95% CI, 0.65-0.98)], in particular men with FH at 40-69 years at age of diagnosis with HR 0.69 (95% CI, 0.49-0.97). The FH population and controls had similar rates of total cancer [HR 0.97 (95% CI, 0.86-1.09)], cancer related to poor diet [HR 0.82 (95% CI, 0.59-1.15)], cancer related to physical inactivity [HR 0.93 (95% CI, 0.73-1.18)], alcohol-related cancer [HR 0.98 (95% CI, 0.80-1.22)] and cancer related to obesity [HR 1.03 (95% CI, 0.89-1.21)]. In summary, we found reduced risk of smoking-related cancer in individuals with FH, most likely due to a lower prevalence of smoking. Implications of these findings can be increased motivation and thus compliance to treatment of hypercholesterolemia.

[The efficacy of secondary prevention programs with remote support in coronary heart disease patients with abdominal obesity].

Background Long-term secondary preventive programs in coronary heart disease (CHD) are of highest efficacy but numerous logistical problems often compromise their implementation. Contemporary remote technologies have a potential to overcome these barriers. AIM: To assess  the impact of 2 preventive counselling programs with subsequent remote support in CHD patients with concomitant obesity. METHODS: A prospective randomized parallel-group study in 120 stable CHD patients hospitalized for elective coronary revascularization who were from 40 to 65 years old and had concomitant obesity. Patients were randomized (1:1:1) into 3 groups (n=40 each). Before discharge, Groups 1 and 2 received a single-session comprehensive counselling with focus on diet followed by remote counselling by phone (Group 1) or via text messages (Group 2). Remote counselling was delivered weekly (Months 1-3) and then monthly (Months 4-6). Group 3 received only standard advice from their attending physicians. The patients were followed for 12 months with assessment of adiposity measures, self-reported dietary patterns, physical activity (IPAQ questionnaire), smoking status, blood pressure (BP), fasting blood glucose, lipids and C-reactive protein (CRP) levels, as well as of clinical events. RESULTS: At 1 year of follow-up, the patients from both intervention groups showed a marked improvement of several risk factors including obesity: the body mass index was reduced by 1.48±0.13 kg/m² in Group 1 and by 1.53±0.18 kg/m² in Group 2; the waist circumference went down by 7.62±0.49 and by 7.41±0.74 cm, respectively; the height-normalized fat mass decreased by 4.66±0.40 kg and 5.98±0.63 kg, respectively (all P values are <0.01 vs corresponding changes in the control group). These changes were coupled with more healthy dietary patterns and less sedentary lifestyles in both intervention groups: the proportion of patients with low activity level fell from 87.5% to 2.5% in Group 1 and from 80% to 10% in Group 2 (both p values <0.01 vs control). In Group 1, BP decreased by 18.08±2.20 mmHg (systolic) and 8.56±1.61 mmHg (diastolic); both р values <0.01 vs Group 3. In Group 2 systolic BP dropped by only 11.95±2.50 mmHg (non-significant) and diastolic BP by 6.33±1.52 mmHg (р<0.05 vs control). The proportion of smokers went down from 30% to 5% in Group 1 and from 22.5% to 0% in Group 2 (both p values <0.01 vs control). The fasting glucose levels decreased by 0.21±0.20 mmol/L in Group 1 and by 0.48±0.25 mmol/L in Group 2 (<0.01 vs control, both), but there were no meaningful improvements in blood lipids or CRP. CONCLUSION: Long-term (6 months) secondary prevention programs incorporating remote support technologies result into sustained improvement of key secondary prevention indicators in obese CHD patients, irrespective of the support modality (by phone or via electronic messaging).

[The Impact of Secondary Prevention Programs Incorporating Remote Technologies on Psychological Well-Being and Quality of Life in Coronary Heart Disease Patients with Abdominal Obesity].

BACKGROUND: Quality of life, which is determined both by the physical symptoms and by psychosocial risk factors, is among the primary treatment goals in coronary heart disease (CHD). Therefore, it is reasonable to assess the impact of any therapeutic interventions in CHD on these measures. AIM: To assess the changes of psychological status and quality of life in patients with CHD and abdominal obesity (AO) over time during 2 secondary prevention programs using two different modalities of remote support. METHODS: An open-label randomized study with 3 parallel groups enrolling hospitalized patients with stable CHD and AO (most hospitalizations were due to elective revascularization procedures). The patients were randomized into 2 intervention groups (Group I and Group II) and into Group III (control). Both intervention groups received secondary prevention programs including one in-hospital preventive counselling session with focus on healthy eating habits and subsequent remote support for 6 months (Month 1 to 3: once a week; Month 4 to 6: once a month). Group I received this subsequent counselling via phone calls and Group II received text messages via different platforms according to patient preferences. Group III received standard advice at discharge only. During 1 year of follow-up motivation for lifestyle changes and continued participation in secondary prevention programs, anxiety and depression symptoms (HADS), stress levels (10-point VAS) and quality of life (HeartQol) were assessed. RESULTS: A total of 120 patients were enrolled (mean age±SD, 57.75±6.25 years; men, 83.4%) who had a high baseline motivation to participate in preventive programs. At 1 year of follow-up there was a substantial improvement in anxiety and depression symptoms in Groups I and II which was absent in Group III. As a result, the proportion of patients with HADS-A score ≥8 dropped from 45.0% to 10.0% in Group I and from 40.0% to 7.5% in Group II (both р values <0.01 vs control), and the proportion of participants with HADS-D ≥8 decreased from 30.0% to 10.0% (р<0.01 vs control) and from  12.5% to 0% (р<0.05 vs control), respectively. Stress level decreased in Groups I and II by 3.95±0.38 and 3.56±0.39 баллов, respectively (both р values <0.01 vs control). The HeartQol global score increased by 1.07±0.08 points in Group I and by 0.98±0.13 points in Group (both р values <0.01 vs control). CONCLUSION: Both secondary prevention programs with long-term remote support targeting obese CHD patients resulted in improvement of pivotal measures of their psychological status i.e. into a decline of anxiety and depression symptomatology, stress reduction and into a better quality of life.

Interactive Nutrition Education Is More Effective in Terms of Improved Levels of Glycated Hemoglobin in Adolescent Patients with Poorly Controlled Type 1 Diabetes - A Randomized Study.

INTRODUCTION: Effectively conducted nutrition education is one of the key elements of the therapy of type 1 diabetes. The aim of the study was to compare the effectiveness of two methods of nutrition education. MATERIAL AND METHODS: A noninvasive interventional randomized single-blind study included 151 patients (13.7±2.2 years old) with poorly controlled type 1 diabetes, treated with the use of insulin pumps. The participants were randomly divided into two groups: a control group (C) in which informative education methods were used (a lecture) and an experimental group (E) in which interactive methods (quiz and multimedia application) were additionally applied. The concentration of glycated hemoglobin (HbA1c) was the primary outcome. The secondary outcomes were: standard deviation score-body mass index (SDS-BMI), standard deviation score-systolic blood pressure (SDS-SBP), standard deviation score-diastolic blood pressure (SDS-DBP), scores of Nutrition Knowledge Survey (NKS) and indices of healthy and unhealthy diet. RESULTS: A marked reduction in HbA1c concentrations was observed after 3 months in group E [-0.47% (-0.77; -0.17), P<0.01; P=0.038 for the intergroup difference]. The positive effect was no longer present after 6 months. No significant changes regarding HbA1c were noted in group C at any stage of the study. After 6 months, both groups obtained better results in one part of NKS ("Blood glucose response to food"): group C [0.41 (0.15; 0.66), P<0.01], group E [0.80 (0.52; 1.08), P<0.001; P=0.042 for the intergroup difference]. No statistically significant differences between groups were noted as regards the remaining parameters. CONCLUSION: Interactive nutrition education is more effective in terms of improved levels of HbA1c in children and adolescents with poorly controlled diabetes. However, an intensification of training frequency is recommended due to the transient effect of education.

Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review.

BACKGROUND: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARß2) gene among breast cancer patients and to review relevant studies in this field in various populations. METHODS: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARß2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. RESULTS: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARß2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). CONCLUSION: We found a higher frequency of RARß2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARß2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer.

An evaluation of randomized controlled trials on nutraceuticals containing traditional Chinese medicines for diabetes management: a systematic review.

BACKGROUND: Nutraceuticals containing traditional Chinese medicine (TCM) are promoted for use in the management of diabetes. The evidence to support such use is largely unknown. This study aimed to summarise and evaluate the literature reporting the results of randomized controlled trials (RCTs) investigating the effects of nutraceuticals in people living with diabetes. METHODS: Literature from four electronic databases (PubMed, Scopus, CINAHL and Web of Science) was searched following PRISMA guidelines to yield RCT publications on nutraceutical for diabetes management published since 2009. The quality of reporting was assessed using the CONSORT 2010 checklist statement. Risk-of-bias for each study was assessed using the Cochrane risk of bias tool. RESULTS: Out of 1978 records identified in the initial search, 24 randomized, double/triple-blinded, controlled trials that investigated the effect of nutraceuticals covering 17 different TCM herbs for diabetes management were selected. Participants included people who were diabetic (n = 16), pre-diabetic (n = 3) or predisposed to diabetes (n = 5). Sample sizes ranged between 23 and 117 for 2 arms, or 99-165 for 3 arms. Comparisons were made against placebo (n = 22), conventional medicine (n = 1), or regular diet (n = 1) for a duration between 4 and 24 weeks. All but one study tested the effect on fasting blood glucose levels (n = 23) or glycated haemoglobin levels (n = 18), and/or postprandial 2-h blood glucose levels (n = 4) as the primary outcomes. Nineteen studies reported some statistically significant reductions in the respective measures while 5 studies showed no effect on primary or secondary outcomes. None of the included studies met all the criteria for the CONSORT guidelines. Incomplete reporting about randomization and blinding, and a lack of ancillary analyses to explore other influential factors and potential harms associated with the use were repeatedly noted. Based on the Cochrane risk-of-bias tool, 19 studies were deemed to have a high risk of bias mainly attributed to sponsor bias. CONCLUSIONS: There is some evidence to suggest positive clinical outcomes in response to the administration of a range of nutraceuticals containing TCM in the management of diabetes. However, these results must be interpreted with caution due to the overall low quality of the trials.

Trimethylamine N-oxide and incident atherosclerotic events in high-risk individuals with diabetes: an ACCORD trial post hoc analysis.

Introduction: Type 2 diabetes mellitus (T2D) confers high atherosclerotic cardiovascular disease (ASCVD) risk. The metabolite trimethylamine N-oxide (TMAO) derived via gut flora has been linked to excess ASCVD. Research design and methods: We analyzed data, biospecimens, and major adverse cardiovascular events (MACEs) from the prospective multicenter randomized Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to assess its value in 330 high-risk individuals with T2D without evident atherosclerotic disease at enrollment. Results: Incident cardiovascular events occurred in 165 cases; 165 controls matched by age, sex, and treatment arm experienced no incident events during follow-up. Cases and controls (mean age 64.5 years) had similar mean glycated hemoglobin (HbA1c) (8.2%) and mean 10-year ASCVD risk (23.5%); groups also had similar use of statins and antihypertensive medications at baseline and follow-up. Baseline plasma TMAO levels did not differ between groups after adjusting for ASCVD risk score, HbA1c, and estimated glomerular filtration rate, nor did TMAO distinguish patients suffering incident MACE from those who remained event-free. Conclusions: TMAO's prognostic value for incident ASCVD events may be blunted when applied to individuals with T2D with poor glycemic control and high baseline ASCVD risk. These results behoove further translational investigations of unique mechanisms of ASCVD risk in T2D.

Effect of motivational interviewing on gestational weight gain and fetal growth in pregnant women with type 2 diabetes.

Objective: To study how lifestyle coaching with motivational interviewing to improve adherence to healthy eating affects gestational weight gain and fetal growth in pregnant women with type 2 diabetes in a real-world setting. Research design and methods: A cohort study including a prospective intervention cohort of consecutive, singleton pregnant, Danish-speaking women with type 2 diabetes included between August 2015 and February 2018 and a historical reference cohort included between February 2013 and August 2015. The intervention consisted of a motivational interviewing to improve adherence to healthy eating in addition to routine care. The reference cohort received routine care only. The main outcomes were gestational weight gain and large for gestational age (LGA) infants. Results: Ninety-seven women were included in the intervention cohort and 92 in the reference cohort. Pre-pregnancy body mass index (32.8±6.9 kg/m2 vs 32.4±7.4 kg/m2, p=0.70), gestational weight gain (9.2±5.8 kg vs 10.2±5.8 kg, p=0.25), HbA1c in early pregnancy (6.7%±1.1% vs 6.5%±1.3% (50±12 mmol/mol vs 48±14 mmol/mol), p=0.32) and late pregnancy (5.9%±0.5% vs 6.0%±0.6% (41±6 mmol/mol vs 42±7 mmol/mol), p=0.34) were comparable in the two cohorts. LGA infants occurred in 20% vs 31%, p=0.07, respectively, and after adjustment for maternal characteristics 14% vs 27% delivered LGA infants (p=0.04). Birth weight z-score was 0.24±1.36 vs 0.61±1.38, p=0.06. Conclusions: Motivational interviewing to improve adherence to healthy eating in addition to routine care in pregnant women with type 2 diabetes tended to reduce fetal overgrowth without major effect on gestational weight gain. Further studies investigating the cost-benefit of enhancing motivation are needed. Trial registration number: NCT02883127.

Comparison of Topical and Intravenous Tranexamic Acid for Total Knee Replacement: A Randomized Double-Blinded Controlled Study of Effects on Tranexamic Acid Levels and Thrombogenic and Inflammatory Marker Levels.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug. Topical administration of TXA during total knee arthroplasty (TKA) is favored for certain patients because of concerns about thrombotic complications, despite a lack of supporting literature. We compared local and systemic levels of thrombogenic markers, interleukin (IL)-6, and TXA between patients who received intravenous (IV) TXA and those who received topical TXA. METHODS: Seventy-six patients scheduled for TKA were enrolled in this randomized double-blinded study. The IV group received 1.0 g of IV TXA before tourniquet inflation and again 3 hours later; a topical placebo was administered 5 minutes before final tourniquet release. The topical group received an IV placebo before tourniquet inflation and again 3 hours later; 3.0 g of TXA was administered topically 5 minutes before final tourniquet release. Peripheral and wound blood samples were collected to measure levels of plasmin-anti-plasmin (PAP, a measure of fibrinolysis), prothrombin fragment 1.2 (PF1.2, a marker of thrombin generation), IL-6, and TXA. RESULTS: At 1 hour after tourniquet release, systemic PAP levels were comparable between the IV group (after a single dose of IV TXA) and the topical group. At 4 hours after tourniquet release, the IV group had lower systemic PAP levels than the topical group (mean and standard deviation, 1,117.8 ± 478.9 µg/L versus 1,280.7 ± 646.5 µg/L; p = 0.049), indicative of higher antifibrinolytic activity after the second dose. There was no difference in PF1.2 levels between groups, indicating that there was no increase in thrombin generation. The IV group had higher TXA levels at all time points (p < 0.001). Four hours after tourniquet release, wound blood IL-6 and TXA levels were higher than systemic levels in both groups (p < 0.001). Therapeutic systemic TXA levels (mean, 7.2 ± 7.4 mg/L) were noted in the topical group. Calculated blood loss and the length of the hospital stay were lower in the IV group (p = 0.026 and p = 0.025). CONCLUSIONS: Given that therapeutic levels were reached with topical TXA and the lack of a major difference in the mechanism of action, coagulation, and fibrinolytic profile between topical TXA and a single dose of IV TXA, it may be a simpler protocol for institutions to adopt the use of a single dose of IV TXA when safety is a concern. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.