Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.

Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment: Comparative Effectiveness Update

Objectives: To update the 2006 systematic review of the comparative benefits and harms of erythropoiesis-stimulating agent (ESA) strategies and non-ESA strategies to manage anemia in patients undergoing chemotherapy and/or radiation for malignancy (excluding myelodysplastic syndrome and acute leukemia), including the impact of alternative thresholds for initiating treatment and optimal duration of therapy. Data sources: Literature searches were updated in electronic databases (n=3), conference proceedings (n=3), and Food and Drug Administration transcripts. Multiple sources (n=13) were searched for potential gray literature. A primary source for current survival evidence was a recently published individual patient data meta-analysis. In that meta-analysis, patient data were obtained from investigators for studies enrolling more than 50 patients per arm. Because those data constitute the most currently available data for this update, as well as the source for on-study (active treatment) mortality data, we limited inclusion in the current report to studies enrolling more than 50 patients per arm to avoid potential differential endpoint ascertainment in smaller studies. Review methods: Title and abstract screening was performed by one or two (to resolve uncertainty) reviewers; potentially included publications were reviewed in full text. Two or three (to resolve disagreements) reviewers assessed trial quality. Results were independently verified and pooled for outcomes of interest. The balance of benefits and harms was examined in a decision model. Results: We evaluated evidence from 5 trials directly comparing darbepoetin with epoetin, 41 trials comparing epoetin with control, and 8 trials comparing darbepoetin with control; 5 trials evaluated early versus late (delay until Hb ≤9 to 11 g/dL) treatment. Trials varied according to duration, tumor types, cancer therapy, trial quality, iron supplementation, baseline hemoglobin, ESA dosing frequency (and therefore amount per dose), and dose escalation. ESAs decreased the risk of transfusion (pooled relative risk [RR], 0.58; 95% confidence interval [CI], 0.53 to 0.64; I2 = 51%; 38 trials) without evidence of meaningful difference between epoetin and darbepoetin. Thromboembolic event rates were higher in ESA-treated patients (pooled RR, 1.51; 95% CI, 1.30 to 1.74; I2 = 0%; 37 trials) without difference between epoetin and darbepoetin. In 14 trials reporting the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale, the most common patient-reported outcome, scores decreased by −0.6 in control arms (95% CI, −6.4 to 5.2; I2 = 0%) and increased by 2.1 in ESA arms (95% CI, −3.9 to 8.1; I2 = 0%). There were fewer thromboembolic and on-study mortality adverse events when ESA treatment was delayed until baseline Hb was less than 10 g/dL, in keeping with current treatment practice, but the difference in effect from early treatment was not significant, and the evidence was limited and insufficient for conclusions. No evidence informed optimal duration of therapy. Mortality was increased during the on-study period (pooled hazard ratio [HR], 1.17; 95% CI, 1.04 to 1.31; I2 = 0%; 37 trials). There was one additional death for every 59 treated patients when the control arm on-study mortality was 10 percent and one additional death for every 588 treated patients when the control-arm on-study mortality was 1 percent. A cohort decision model yielded a consistent result—greater loss of life-years when control arm on-study mortality was higher. There was no discernible increase in mortality with ESA use over the longest available followup (pooled HR, 1.04; 95% CI, 0.99 to 1.10; I2 = 38%; 44 trials), but many trials did not include an overall survival endpoint and potential time-dependent confounding was not considered. Conclusions: Results of this update were consistent with the 2006 review. ESAs reduced the need for transfusions and increased the risk of thromboembolism. FACT-Fatigue scores were better with ESA use but the magnitude was less than the minimal clinically important difference. An increase in mortality accompanied the use of ESAs. An important unanswered question is whether dosing practices and overall ESA exposure might influence harms.

Treatment with tumor necrosis factor inhibitors in axial spondyloarthritis: comparison between private rheumatology practices and academic centers in a large observational cohort

OBJECTIVE To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers. METHODS We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort. RESULTS All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0). CONCLUSION With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

German Total Ankle Replacement Register of the German Foot and Ankle Society (D. A. F.) - presentation of design and reliability of the data as well as first results

INTRODUCTION Even though arthroplasty of the ankle joint is considered to be an established procedure, only about 1,300 endoprostheses are implanted in Germany annually. Arthrodeses of the ankle joint are performed almost three times more often. This may be due to the availability of the procedure - more than twice as many providers perform arthrodesis - as well as the postulated high frequency of revision procedures of arthroplasties in the literature. In those publications, however, there is often no clear differentiation between revision surgery with exchange of components, subsequent interventions due to complications and subsequent surgery not associated with complications. The German Orthopaedic Foot and Ankle Association's (D. A. F.) registry for total ankle replacement collects data pertaining to perioperative complications as well as cause, nature and extent of the subsequent interventions, and postoperative patient satisfaction. MATERIAL AND METHODS The D. A. F.'s total ankle replacement register is a nation-wide, voluntary registry. After giving written informed consent, the patients can be added to the database by participating providers. Data are collected during hospital stay for surgical treatment, during routine follow-up inspections and in the context of revision surgery. The information can be submitted in paper-based or online formats. The survey instruments are available as minimum data sets or scientific questionnaires which include patient-reported outcome measures (PROMs). The pseudonymous clinical data are collected and evaluated at the Institute for Evaluative Research in Medicine, University of Bern/Switzerland (IEFM). The patient-related data remain on the register's module server in North Rhine-Westphalia, Germany. The registry's methodology as well as the results of the revisions and patient satisfaction for 115 patients with a two year follow-up period are presented. Statistical analyses are performed with SAS™ (Version 9.4, SAS Institute, Inc., Cary, NC, USA). RESULTS About 2½ years after the register was launched there are 621 datasets on primary implantations, 1,427 on follow-ups and 121 records on re-operation available. 49 % of the patients received their implants due to post-traumatic osteoarthritis, 27 % because of a primary osteoarthritis and 15 % of patients suffered from a rheumatic disease. More than 90 % of the primary interventions proceeded without complications. Subsequent interventions were recorded for 84 patients, which corresponds to a rate of 13.5 % with respect to the primary implantations. It should be noted that these secondary procedures also include two-stage procedures not due to a complication. "True revisions" are interventions with exchange of components due to mechanical complications and/or infection and were present in 7.6 % of patients. 415 of the patients commented on their satisfaction with the operative result during the last follow-up: 89.9 % of patients evaluate their outcome as excellent or good, 9.4 % as moderate and only 0.7 % (3 patients) as poor. In these three cases a component loosening or symptomatic USG osteoarthritis was present. Two-year follow-up data using the American Orthopedic Foot and Ankle Society Ankle and Hindfoot Scale (AOFAS-AHS) are already available for 115 patients. The median AOFAS-AHS score increased from 33 points preoperatively to more than 80 points three to six months postoperatively. This increase remained nearly constant over the entire two-year follow-up period. CONCLUSION Covering less than 10 % of the approximately 240 providers in Germany and approximately 12 % of the annually implanted total ankle-replacements, the D. A. F.-register is still far from being seen as a national registry. Nevertheless, geographical coverage and inclusion of "high-" (more than 100 total ankle replacements a year) and "low-volume surgeons" (less than 5 total ankle replacements a year) make the register representative for Germany. The registry data show that the number of subsequent interventions and in particular the "true revision" procedures are markedly lower than the 20 % often postulated in the literature. In addition, a high level of patient satisfaction over the short and medium term is recorded. From the perspective of the authors, these results indicate that total ankle arthroplasty - given a correct indication and appropriate selection of patients - is not inferior to an ankle arthrodesis concerning patients' satisfaction and function. First valid survival rates can be expected about 10 years after the register's start.

Predicting Psychotherapy Dropouts: A Multilevel Approach

The role of therapeutic processes in predicting premature termination of psychotherapy has been a particular focus of recent research. The purpose of this study was to contrast outpatients who completed therapy and those who dropped out with respect to their self-reported in-session experiences of self-esteem, mastery, clarification and the therapeutic alliance. The 296 patients with mixed disorders were treated with an integrative form of cognitive–behavioural therapy without pre-determined time limit (M = 20.2 sessions). Multilevel analyses indicated that patients who did not completetreatment reported, on average, lower levels of self-esteem, mastery and clarification and lower ratings of their therapeutic alliance in treatment in contrast to patients who completed therapy. Patient-reported change in self-esteem experiences over the course of treatment turned out to be the strongest predictor of dropout from psychotherapy or successful completion. When dropout occurred before the average treatment length was reached, patients reported fewer clarifying experiences as early as the first session and their ratings of the therapeutic alliance were characterized by an absence of positive development. Both of these aspects seem to be involved in patients' decisions to leave treatment early. The findings underscore the importance of the therapeutic process in understanding the mechanisms behind treatment dropout. Copyright © 2014 John Wiley & Sons, Ltd.

Detection of the pan neuronal marker PGP9.5 by immuno-histochemistry and quantitative PCR in eutopic endometrium from women with and without endometriosis.

PURPOSE To assess endometrial gene as well as protein expression of neuroendocrine and supposedly endometriosis-associated product PGP9.5 and pain symptoms in women with endometriosis and controls undergoing laparoscopy, using molecular biological and immuno-histochemical approaches in the same patients. METHODS Biopsy of eutopic endometrium from 29 patients by sharp curettage, and preparation of paraffin blocks. Determination of PGP9.5 gene expression and protein abundance using qPCR and immuno-histochemistry. RESULTS qPCR; The PGP9.5 mRNA expression level between women with (N = 16) and without (N = 13) endometriosis was not different, regardless of pain symptoms or menstrual cycle phase. PGP9.5 expression was higher in women who reported pain compared to those who did not; however, this association was not statistically significant. The expression of PGP9.5 mRNA was higher in women with endometriosis and pain during the proliferative than in the secretory phase (P = 0.03). Furthermore, in the first half of the cycle, the abundance of the PGP9.5 transcript was also significantly higher in endometriosis patients compared to those without (P = 0.03). Immuno-histochemistry; Thirteen of the 16 endometriosis patients showed positive PGP9.5 immuno-reactivity in the endometrium, whereas no such signal was observed in women without endometriosis. The absolute number of nerve fibres per mm(2) in women with endometriosis was similar, regardless of the pain symptoms. CONCLUSIONS PGP9.5 mRNA expression is increased in the proliferative phase of endometriotic women with pain. The presence of nerve fibres was demonstrated by a PGP9.5 protein signal in immuno-histochemistry and restricted to patients with endometriosis. Based on these results, however, there did not appear to be a direct association between the gene expression and protein abundance in women with and without endometriosis or those that experienced pain.

Periodontal regeneration - furcation defects: a consensus report from the AAP Regeneration Workshop

BACKGROUND Treatment of furcation defects is a core component of periodontal therapy. The goal of this consensus report is to critically appraise the evidence and to subsequently present interpretive conclusions regarding the effectiveness of regenerative therapy for the treatment of furcation defects and recommendations for future research in this area. METHODS A systematic review was conducted before the consensus meeting. This review aims to evaluate and present the available evidence regarding the effectiveness of different regenerative approaches for the treatment of furcation defects in specific clinical scenarios compared with conventional surgical therapy. During the meeting, the outcomes of the systematic review, as well as other pertinent sources of evidence, were discussed by a committee of nine members. The consensus group members submitted additional material for consideration by the group in advance and at the time of the meeting. The group agreed on a comprehensive summary of the evidence and also formulated recommendations for the treatment of furcation defects via regenerative therapies and the conduction of future studies. RESULTS Histologic proof of periodontal regeneration after the application of a combined regenerative therapy for the treatment of maxillary facial, mesial, distal, and mandibular facial or lingual Class II furcation defects has been demonstrated in several studies. Evidence of histologic periodontal regeneration in mandibular Class III defects is limited to one case report. Favorable outcomes after regenerative therapy for maxillary Class III furcation defects are limited to clinical case reports. In Class I furcation defects, regenerative therapy may be beneficial in certain clinical scenarios, although generally Class I furcation defects may be treated predictably with non-regenerative therapies. There is a paucity of data regarding quantifiable patient-reported outcomes after surgical treatment of furcation defects. CONCLUSIONS Based on the available evidence, it was concluded that regenerative therapy is a viable option to achieve predictable outcomes for the treatment of furcation defects in certain clinical scenarios. Future research should test the efficacy of novel regenerative approaches that have the potential to enhance the effectiveness of therapy in clinical scenarios associated historically with less predictable outcomes. Additionally, future studies should place emphasis on histologic demonstration of periodontal regeneration in humans and also include validated patient-reported outcomes. CLINICAL RECOMMENDATIONS Based on the prevailing evidence, the following clinical recommendations could be offered. 1) Periodontal regeneration has been established as a viable therapeutic option for the treatment of various furcation defects, among which Class II defects represent a highly predictable scenario. Hence, regenerative periodontal therapy should be considered before resective therapy or extraction; 2) The application of a combined therapeutic approach (i.e., barrier, bone replacement graft with or without biologics) appears to offer an advantage over monotherapeutic algorithms; 3) To achieve predictable regenerative outcomes in the treatment of furcation defects, adverse systemic and local factors should be evaluated and controlled when possible; 4) Stringent postoperative care and subsequent supportive periodontal therapy are essential to achieve sustainable long-term regenerative outcomes.

Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS It is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission. METHODS Between April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score <20 (range, 0-100); histologic remission was defined as a peak count of <20 eosinophils/mm(2) in a high-power field (corresponds to approximately <5 eosinophils/median high-power field); and endoscopic remission as absence of white exudates, moderate or severe rings, strictures, or combination of furrows and edema. We used receiver operating characteristic analysis to determine the best symptom score cutoff values for detection of remission. RESULTS Of the study subjects, 111 were in clinical remission (41.3%), 79 were in endoscopic remission (29.7%), and 75 were in histologic remission (27.9%). When the symptom score was used as a continuous variable, patients in endoscopic, histologic, and combined (endoscopic and histologic remission) remission were detected with area under the curve values of 0.67, 0.60, and 0.67, respectively. A symptom score of 20 identified patients in endoscopic remission with 65.1% accuracy and histologic remission with 62.1% accuracy; a symptom score of 15 identified patients with both types of remission with 67.7% accuracy. CONCLUSIONS In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone. At any given time, physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults with EoE. ClinicalTrials.gov, Number: NCT00939263.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

Standardized pelvic floor exercises improve stress urinary incontinence in women with intrinsic sphincter deficiency.

OBJECTIVES Pelvic floor rehabilitation is the conservative therapy of choice for women with stress urinary incontinence (SUI). The success rate of surgical procedures in SUI patients with intrinsic sphincter deficiency (ISD) is low. The aim of this study was to analyse the effect of a standardized physiotherapy on patients with SUI and normotonic urethra and ISD. METHODS In this study, 64 patients with ISD and 69 patients with normotonic urethra were enrolled. Maximum urethral pressure (MUCP) >20 cm H2 O was considered as normotonic urethral pressure. Before and after physiotherapy MUCP was measured and cough testing was performed. Additionally, patient reported outcome was assessed using the King's Health Questionnaire (KHQ). For statistical analyses Excel 2010 (Microsoft Inc; Redmond, Washington) and SPSS 20 (SPSS Inc; Chicago, Illinois) for Windows were used. Power calculation was based on the primary endpoint incontinence impact and general health. For power calculation, GraphPad Statmate version 2.00 for Windows was used. RESULTS Sixty-four patients with ISD and 69 patients with normotonic urethra were included in the study. In SUI patients with normotonic and hypotonic urethra KHQ-scores regarding the primary endpoins "general health" and "incontinence impact" significantly improved following standardized physiotherapy. In both groups MUCP increased after physiotherapy. In SUI patients with ISD standardized physiotherapy resulted in a decreased incidence of a positive cough test. CONCLUSIONS Standardized physiotherapy should be offered to patients with SUI and ISD. Long-term results are subject to future studies. Neurourol. Urodynam. © 2015 Wiley Periodicals, Inc.

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of "omic" datasets that are at the core of this systems medicine approach.

Treatment discontinuation among breast, colorectal, and prostate cancer patients in Alabama

Introduction. Cancer registries provide information about treatment initiation but not the full course of treatment. In an effort to identify patient reported reasons for discontinuing cancer treatment, patients with prostate, breast, and colorectal cancer were identified from Alabama State Cancer Registry (ASCR) -Alabama Medicare linked database for interview. This study has two specific aims: (1) determine whether the ASCR-Medicare database accurately reflects patients’ treatment experiences in terms of whether they started and completed treatment when compared to patient self-report and (2) determine which patient demographic and health care system factors are related to treatment completion as defined by patient self-report. ^ Methods. The ASCR-Medicare claims dataset supplemented patient interview responses to identify treatment initiation and completion among prostate, breast, and colorectal cancer patients in Alabama from 1999-2003. Kappa statistic was used to test for concordance of treatment initiation and completion between patient self-report and Medicare claims data. Patients who reported not completing treatment were asked questions to ascertain reasons for treatment discontinuation. Logistic regression models were constructed to explore the association of patient and tumor characteristics with discontinuation of radiation and chemotherapy. ^ Results. Overall, there was a fair agreement across all cancer sites about whether one had surgery (Kappa=.382). There was fair agreement between self-report and Medicare claims data for starting radiation treatment (Kappa=.278). For starting chemotherapy there was moderate agreement (Kappa=.414). There was no agreement for completing treatment for radiation and chemotherapy between the self-report and claims data. Patients most often reported doctor’s recommendation (40% for radiation treatment and 21.4% for chemotherapy) and side effects (30% for radiation treatment and 42.8% for chemotherapy) for discontinuing treatment. Females were less likely to complete radiation than males (OR=.24, 95% CI=.11–.50). Stage I patients were more likely to drop radiation treatment than stage III patients (OR=3.34, 95% CI=1.12–9.95). Younger patients were more likely to discontinue chemotherapy than older patients (OR=2.84 95%, CI=1.08–7.69) and breast cancer patients were less likely to discontinue chemotherapy than colorectal patients (OR=.13, 95% CI=.04–.46). ^ Conclusion. This study reveals that patients recall starting treatment more accurately than completing treatment and that there are several demographic and tumor characteristics that influence treatment discontinuation. Providing patients with treatment summaries and survivorship plans can help patients their follow-up care when there are gaps in treatment recall and discontinuation of treatment.^

Avaliação dos efeitos do tratamento periodontal não cirúrgico sobre os sinais e sintomas da síndrome de Sjögren primária

A síndrome de Sjögren primária (SSp) é uma doença crônica autoimune sistêmica que pode levar à hipossalivação e afetar negativamente o ambiente oral. Os objetivos deste estudo foram detectar a influência da SSp nos níveis de biomarcadores inflamatórios na saliva e no fluido gengival nas amostras de pacientes com periodontite crônica, avaliar o efeito do tratamento periodontal não cirúrgico sobre os valores do índice clínico de avaliação da atividade sistêmica de pacientes com SSp e do índice reportado pelo paciente com SSp. Amostras de fluido gengival, saliva e os parâmetros clínicos periodontais que consistiram de medida da profundidade de sondagem (PS), nível clínico de inserção (NCI), sangramento à sondagem (SS) e índice de placa (IP) foram coletadas no início do estudo e 45 dias após a terapia periodontal não-cirúrgica de pacientes sistemicamente saudáveis com periodontite crônica (PC, n = 7) e pacientes com SSp e periodontite crônica (SP, n = 7). Pacientes periodontalmente saudáveis com SSp (SC, n = 7) e sistemicamente saudáveis (C, n = 7) também foram avaliados no início do estudo. Os grupos C, PC e SC foram pareados em gênero, idade e critério socioeconômico com o grupo SP. Os níveis de interleucina-8 (IL-8), IL-10 e IL-1ß foram avaliados por ensaio multiplex. Os níveis de atividade da doença foram medidos usando o Gold Standard da literatura chamado Índice Eular de atividade da síndrome de Sjögren (ESSDAI). Já para avaliação dos sintomas reportados pelo paciente com SSp foi utilizado o Índice Eular reportado pelo paciente com Sjögren (ESSPRI). Os parâmetros clínicos melhoraram após a terapia periodontal (p <0,05). No entanto, o NCI em pacientes com SSp não melhorou significativamente após a terapia (p> 0,05). Houve um aumento nos níveis de IL-1ß, IL-8 e diminuição dos níveis de IL-10 nas amostras de saliva de pacientes do grupo SC em comparação ao grupo C (p <0,05). Já em relação ao fluido gengival, pacientes do grupo SC tiveram maiores níveis de IL-1ß em comparação com o grupo C (p<0,05). Além disso, o tratamento periodontal não cirúrgico resultou num aumento dos níveis de IL-10 no fluido gengival no grupo SP e grupo PC em relação ao valor basal (p <0,05). O fluxo salivar foi significativamente aumentado após o tratamento periodontal apenas em pacientes do grupo SP (p = 0,039). Além disso, o tratamento periodontal não influenciou o índice ESSDAI (p = 0,35) e levou a uma diminuição significativa no índice ESSPRI (p = 0,03). Os presentes dados demonstraram que a SSp influencia os níveis salivares e de fluido gengival de biomarcadores inflamatórios em favor de um perfil próinflamatório, no entanto, este perfil parece não aumentar susceptibilidade dos indivíduos SSp à destruição periodontal. Além disso, os presentes dados demonstraram que o tratamento periodontal não-cirúrgico tem um impacto positivo sobre o fluxo salivar e sobre o índice ESSPRI de pacientes com SSp. Sugere-se assim que o tratamento periodontal pode melhorar a qualidade de vida de indivíduos com SSp.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

The development of psychological changes following whiplash injury

Psychological distress is a feature of chronic whiplash-associated disorders, but little is known of psychological changes from soon after injury to either recovery or symptom persistence. This study prospectively measured psychological distress (General Health Questionnaire 28 GHQ-28). fear of movement/re-injury (TAMPA Scale of Kinesphobia, TSK), acute post-traumatic stress (Impact of Events Scale, IES) and general health and well being (Short Form 36, SF-36) in 76 whiplash subjects within I month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered (< 8), mild pain and disability (10-28) or moderate/severe pain and disability (> 30). All whiplash groups demonstrated psychological distress (GHQ-28, SF-36) to some extent at 1 month post-injury. Scores of the recovered group and those with persistent mild symptoms returned to levels regarded as normal by 2 months post-injury, parallelling a decrease in reported pain and disability. Scores on both these tests remained above threshold levels in those with ongoing moderate/severe symptoms. The moderate/severe and mild groups showed elevated TSK scores at 1 month post-injury. TSK scores decreased by 2 months in the group with residual mild symptoms and by 6 months in those with persistent moderate/severe symptoms. Elevated IES scores, indicative of a moderate post-traumatic stress reaction, were unique to the group with moderate/severe symptoms. The results of this study demonstrated that all those experiencing whiplash injury display initial psychological distress that decreased in those whose symptoms subside. Whiplash participants who reported persistent moderate/severe symptoms at 6 months continue to be psychologically distressed and are also characterised by a moderate post-traumatic stress reaction. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.