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A review of 75 original articles from clinical cancer research in Norway is presented. Articles published in 1993 and with at least one Norwegian author were included in the review. Sixty papers were observational, whereas 15 were experimental. Of the observational studies 44 were retrospective. Most of the papers concerned prognostic factors. Prior hypotheses were explicitly defined in 16 papers only, and less than half of the articles described inclusion and exclusion criteria. Sample size calculations were performed in four papers only. The choice of statistical method was considered to be suitable in 22 of the 58 articles presenting statistical inferences. Problems related to multiple significance testing were rarely addressed, although the median number of p-values reported was as high as 8. Confidence intervals for main findings were presented in 14 papers. For proper planning of studies, as well as for analysis and interpretation of study results, statistical advice is indeed required. [ABSTRACT FROM AUTHOR]

Performing a reliable assessment of chronic pruritus remains a challenge. Electronic diaries are often used, but many of the scales have not been validated. ItchApp© was developed for Android smartphones in order to address this lack. A total of 40 subjects with chronic pruritus completed questionnaires both on paper and with ItchApp© (verbal rating scale, numerical rating scale, dynamic pruritus score) in order to validate the software application. Strong correlations were found for test–retest reliability (intraclass correlation coefficient: 0.865-0.977) and convergent validity (Spearman's r: 0.442-0.924). A feasibility questionnaire for ItchApp© revealed a high level of user friendliness and compliance. This was confirmed in a randomized controlled trial with 68 subjects, for which the clinically important difference in the numerical rating scale values for ItchApp© was calculated (2.61 points). In summary, ItchApp© is a recently developed eDiary that can provide experts with a reliable evaluation of patients with chronic pruritus. It will be made available for future clinical trials. [ABSTRACT FROM AUTHOR]

To investigate how urological studies using composite endpoints as the primary outcome were cited. In this quality analysis of citations, three randomized clinical trials each investigating oncological and non-oncological urology were selected for citation analysis based on pre-defined criteria. In total, 531 papers citing the selected studies were reviewed; citations were evaluated based on whether they correctly referred to the composite endpoint and if singleton endpoints were defined and/or discussed. Among the citations, 223/531 (42%) referred to the composite endpoint, of which 217/223 (97.3%) correctly cited the composite endpoint. However, only 91/217 (41.9%) defined and/or discussed the singleton endpoints of the composite endpoint. The lack of a validated instrument for citation analysis was a limitation of this study. Meanwhile, the main strength is the large number of individually analyzed citations. The composite endpoints of urological randomized clinical trials are generally cited without referring to the composite endpoint; when cited, the composite endpoints are described correctly. However, in most cases, without defining or discussing the singleton endpoints. [ABSTRACT FROM AUTHOR]

In the Nordic countries, as in the rest of the world, particle therapy as a radiotherapy modality, is evolving, albeit the hard evidence for the clinical benefit still is scarce. However, a common goal for the Nordic countries is to include a minimum of 80% of the patients treated with particle therapy into clinical trials. In this paper, we summarize the current status of clinical trials involving particle therapy in the Nordic countries, with an overview of both active and coming trials. So far, one is closed for inclusion and data are being analyzed, seven trials are actively recruiting patients and several more trials are underway. No common Nordic trial has yet been designed, nor is in the planning phase, and the authors will discuss the obstacles as well as the opportunities a common Nordic platform may represent. [ABSTRACT FROM AUTHOR]

The article presents summaries of several papers which were presented at the 2010 World Health Organization International Consultation on Prostate Cancer. The papers centered on advances in screening, prevention and therapy for prostate cancer and discussed the future challenges of prostate cancer and its prevention and treatment.

Objective. To evaluate the scientific evidence regarding laser technology for removal of carious tissue. Material and methods. A search for literature on the effect of treatment and on economic aspects of laser technology identified 23 papers. No relevant studies on economic aspects were found. Regarding the effect of treatment, 16 papers were selected for assessment according to established criteria. Results. Cavity preparation and caries excavation by erbium laser were evaluated in three studies of medium quality. The time required to remove carious tissue was evaluated in five studies assessed as being of medium quality for this outcome. In four studies the effect of laser treatment on the dental pulp was included as an outcome but, due to the short follow-up time, the quality was assessed as low. Two studies that included the longevity of the restoration as an outcome were also assessed as being of low quality because the follow-up time was inadequate. Patient response was evaluated in three studies, which were assessed as being of medium quality with respect to this outcome. Conclusions. There is limited scientific evidence that laser treatment is as effective as a rotary bur for removing carious tissue. Treatment time is prolonged. There is limited scientific evidence that adults prefer laser treatment. No conclusions can be drawn regarding biological or technical complications, children's perception of laser treatment or the cost-effectiveness of the method. [ABSTRACT FROM AUTHOR]

Chronic pruritus is a common symptom and there is an urgent need to test new anti-pruritic substances in highquality clinical trials. However, no widely accepted standardized and validated method for objectively measuring pruritus is yet available. A special interest group of the International Forum for the Study of Itch has been established to assess scoring methods and questionnaires for use in clinical trials. This paper presents our current recommendations. The set of measures we recommend includes pruritus intensity scales, instruments for assessment of scratch lesions, chronic pruritus course, quality of life and patient benefitsen. [ABSTRACT FROM AUTHOR]

Background. Determining the non-inferiority margin is an essential step in the design and interpretation of non-inferiority trials, and this margin should be preferably justified on clinical and statistical grounds. Methods. After a PubMed search for phase III trials in advanced breast cancer (BC) or non-small cell lung cancer (NSCLC) published between January 1998 and December 2009 in 11 leading journals, non-inferiority trials were selected by manual search of the full papers. Results. Twenty-four of 195 trials had a primary non-inferiority hypothesis. When the two six-year study periods were compared, there were time trends within BC and NSCLC, with most non-inferiority trials in BC reported in the first six-year period, and vice-versa for NSCLC. The median sample size was larger for non-inferiority than superiority trials (p < 0.01). The choice of a non-inferiority margin was reportedly justified in only five cases. Non-inferiority trials were more likely than superiority trials to yield positive results (p < 0.001), as were trials in breast cancer (p = 0.02). Conclusions. Non-inferiority margins for cancer trials appear to be chosen mostly on historical grounds. Since nearly three-quarters of non-inferiority trials achieve their primary objective, the extent to which the choice of margins has influence on trial results remains to be determined. [ABSTRACT FROM AUTHOR]

Objective: Concerns over adverse effects of mercury released from dental amalgam sometimes lead patients to request removal of their amalgam restorations. Several studies report improvement of subjective health after removal of amalgam restorations, but the mechanisms are unclear. The aim of this paper is to present data on long term changes in intensity of health complaints after amalgam removal in a group of patients with health complaints self-attributed to dental amalgam. Data from the five years follow-up in a clinical trial are presented and related to potential determinants of change.Materials and Methods: Patients previously referred to a specialty unit for health complaints attributed to amalgam restorations were included in the study. The 20 participants who were allocated to the treatment group had all amalgam restorations removed and replaced with other dental restorative materials. Intensity of health complaints was calculated from questionnaire data and personality variables were measured by MMPI-2.Results: At the follow-up five years after the amalgam removal was completed, intensity of general health complaints was significantly reduced (p=.001), but the symptom load was still high. The reduction was significantly correlated with concentration of mercury in urine at pre-treatment. There were no significant correlations with personality variables.Conclusions: Removal of amalgam restorations was followed by a long term reduction of general health complaints, which was associated with mercury concentration in urine before amalgam removal. Additional studies are needed to confirm the potential mechanisms for the observed reduction. [ABSTRACT FROM AUTHOR]

Background and purpose — Custom triflange acetabular components (CTACs) are suggested as good solutions for large acetabular defects in revision total hip arthroplasty. However, high complication rates have been reported and most studies are of limited quality. This prospective study evaluates the performance of a CTAC in patients with large acetabular defects including pelvic discontinuity. Patients and methods — Prospectively collected data of 49 consecutive patients (50 hips), who underwent an acetabular revision with a CTAC were analyzed. Follow-up (FU) was 2 years. The median age of the patients was 68 years (41–89) and 41 were women. Primary outcomes were re-revision of the CTAC and differences between the modified Oxford Hip Score (mOHS) preoperatively and at 2-year follow-up. Secondary outcomes included several patient-reported outcomes (PROMs), radiological results, complications, and a comparison between hips with and without pelvic discontinuity (PD). Results — 1 patient (1 hip) was lost to the 2-year FU. No CTAC needed re-revision. The preoperative and 2-year FU mOHS were available in 40 hips and improved statistically significantly. All of the other secondary outcomes improved over time. 5 hips (of 45 with radiological 2-year FU) had loosening of screws. 8 hips had complications, including 3 persistent wound leakage, 3 pelvic fractures, and 1 dislocation. The mOHS and complication rate were similar in hips with and without PD. Interpretation — Reconstruction of large acetabular defects with and without PD with this CTAC showed good improvement in patient-reported daily functioning, high patient-reported satisfaction, few complications, and no re-revisions at 2-year FU. [ABSTRACT FROM AUTHOR]

Compared to non-smokers, smokers have reduced effects of cancer treatment, and increased risk of treatment-related toxicity. Quitting smoking can improve treatment effects and reduce side effects. This study reports on the potential impact of a smoking cessation program on smoking cessation rates among patients in cancer treatment. Cancer patients 18 years and older who smoked, with survival prognosis ≥12 months, not suffering dementia or other mental illness, and who were referred to cancer treatment at six Norwegian hospitals were invited to participate. The study took place from 2017 to 2020 and used a pre-test-posttest non-equivalent control group design. The intervention group received structured smoking cessation guidance based on Motivational Interviewing combined with cost-free nicotine replacement products, while the control group received standard smoking cessation treatment. Self-reported smoking status were registered at baseline and at 6 months' follow up. 76% of patients smoked at baseline and 44% at follow-up in the intervention group, correspondingly 72% and 49% in the control group. In an analysis of differences in within-person change, the reduction in the intervention group was 13 percentage points larger (95% CI = (0.25, −0.005), p = 0.041). Adjusting for gender, age, education, labour market participation and partnership status did not attenuate the estimated effect (18 percentage point difference, 95% CI = (−0.346, −0.016), p = 0.032). Demographic factors and dropout rate differed somewhat between the groups with a higher dropout rate in the intervention group, 54% vs. 51%, respectively). Offering a structured smoking cessation program based on Motivational Interviewing and cost-free nicotine replacement products to cancer patients can increase cessation rates in comparison to standard smoking cessation care. [ABSTRACT FROM AUTHOR]

Using real-world (RW) data from registries to mimic or substitute a comparator arm of clinical trials is increasingly investigated. The feasibility of using data sources for this purpose depends on the source's completeness of the wide spectrum of a disease characteristics and relevant endpoints, which could allow for proper matching of important variables. This is a Norwegian study using data from three population-based registries, the Cancer Registry (CRN), the National Patient Registry (NPR), and the Norwegian Prescribed Drug Registry (LMR). We assessed if the registries contained the information necessary for selecting a RW cohort of patients with characteristics that mimicked the inclusion and exclusion criteria from the control arm of the phase 3 trial (KeyNote-407) on patients with stage IV, squamous NSCLC. We did this both on an aggregated - and individual data level. We also described the survival in the RW-cohorts and compared it with the survival in the control arm of the KN-407 trial. Using aggregated data from the CRN allowed us to find the patients based on some clinically relevant inclusion criteria, but only to a limited extent could we apply the exclusion criteria of KN-407. When we used individual data from the CRN, NPR and the LMR we could create a patient cohort that shared more criteria corresponding to the eligibility criteria from KN-407, including exclusion criteria. Compared to the 11.3 months (CI 95% 9.5, 14.8) median survival in the control arm of KN-407, both RW-cohorts had a shorter median survival, 7.07 months (CI 95% 6.7, 9.5) (individual) and 8.0 months (CI 95% 5.8, 10.5) (aggregated). Even if we demonstrated that the registries contain clinically relevant information necessary to mimic the eligibility criteria of a selected RCT, the survival is shorter for RW patients compared to their control arm counterpart in the RCT. [ABSTRACT FROM AUTHOR]

BackgroundColorectal cancer (CRC) is a disease of the older population. The current demographic ageing leads to more elderly patients and is expected to further increase the number of patients with CRC. The objective of the present paper is to outline incidence, mortality and prevalence from 1980 to 2012 and survival data from 1968 to 2012 in Danish CRC patients focusing on the impact of ageing. Material and methodsData were derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data are delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. This study focuses on the elderly population categorized in six age groups. ResultsThe incidence of CRC has increased over the past three decades. Incidence rate has increased in patients with colon cancer, but showed a decreasing trend in the oldest patients with rectal and anal cancer. Mortality has diminished in younger patients with colon cancer, but increased with increasing age. However, mortality did not increase proportionally to incidence. In rectal and anal cancer mortality has decreased, except among the oldest patients. This correlates to a decreasing incidence rate. Prevalence is widely increasing mainly because of increased incidence and longer survival, which is reflected in the increasing one- and five-year age-specific relative survival after a diagnosis of colon, rectal and anal cancer. ConclusionThe incidence of CRC is increasing, especially in older citizens, and mortality increases with older age. There is limited knowledge on how to optimize treatment in older CRC patients and future focus must be how to select and tailor the treatment for older CRC patients. [ABSTRACT FROM PUBLISHER]

A systematic review of published data was conducted with the aim of assessing effects of xylitol and erythritol consumption on levels of mutans streptococci (MS) and the oral microbiota. Electronic and hand searches were performed to find clinical microbiological studies concerning the consumption of xylitol and erythritol chewing gum or candies, and published between 2000 and 2019. Prospective randomized controlled clinical trials conducted in healthy subjects were included in the review. The initial search identified 561 xylitol and 83 erythritol studies. After applying inclusion and exclusion criteria, 21 xylitol studies and one erythritol study were reviewed. The review identified nine xylitol studies with a fair or high quality, four conducted in children and five in adults, all demonstrating a decrease in MS levels in association with habitual consumption of xylitol. The three microbiota studies employing multispecies probe approaches revealed no effects for xylitol on the microbiota. The only erythritol study fulfilling the inclusion criteria showed no consistent effects on MS levels. Xylitol consumption is likely to decrease MS counts but it may not change the overall microbiota. Xylitol shows thus properties of an oral prebiotic. More studies are needed to demonstrate the effects of erythritol on MS. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effectiveness of an upper removable appliance in the treatment of an anterior crossbite in term of quality of life, effectiveness, treatment time, long term stability and cost minimization.Design: Systematic reviewData source: A search strategy was implemented using both manual hand search and electronic databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, ScienceDirect, Scopus and Ebsco.Study eligibility criteria: Randomized controlled clinical trialsParticipants: Children in the early or late mixed dentition with an anterior crossbite affecting one or more incisors, and no underlying skeletal class III pattern.Interventions: Upper removable appliance compared with other orthodontic appliances.Study appraisal and synthesis: All potential articles were checked against the inclusion criteria independently, and in duplicate by two investigators. Risk of bias of eligible studies to be included in the final analysis was assessed independently by two authors using Cochrane risk of bias tool.Results: A total of 524 articles were identified in both manual and electronic searches as well as by checking the reference lists of the final articles to be included in the study. Only 7 reports of 3 RCTs met the inclusion criteria and thus were included in the final analysis. All but one of the 3 RCTs were judged to be of very low quality. No statistical methods were employed to combine the studies due to the heterogeneity of the studies.Conclusion: A fixed appliance was more cost-effective than a removable appliance in the correction of an anterior crossbite with a functional shift. There was no significant difference in terms of quality of life, pain intensity or long-term stability between the two appliances. On the other hand, both a removable appliance and cemented bite-pads were equally effective in the correction of an anterior dental crossbite without having any side effect. [ABSTRACT FROM AUTHOR]

Chronic pruritus is a frequent global condition. The pathophysiology, underlying aetiology, clinical manifestation, associated burden and response to therapy of chronic pruritus varies from patient to patient, making clinical research and management of this condition challenging. There are still several unmet needs, such as the need to standardize translational research protocols, diagnostic and therapeutic procedures and to enhance the knowledge of the humanistic and economic burden associated with chronic pruritus. Basic and clinical research is of the utmost importance to target these matters. Clinical research has the potential to identify new relevant mechanisms in affected patients, which may lead to identification of novel therapy targets. This article discusses in depth current shortcomings in the daily care of patients with chronic pruritus and the challenges clinical researchers and physicians treating chronic pruritus face in addressing these matters. [ABSTRACT FROM AUTHOR]

Background. In 2009, the European Randomized Study of Screening for Prostate Cancer (ERSPC) was one of two studies to report interim data on the effect of screening for prostate cancer (PC) on the disease specific mortality. Contradictory results caused considerable discussion and misunderstanding in secondary literature. Methods. This document is based on a non systematic review of recent evidence for and against screening for PC, specifically considering three recently published randomized screening trials [1 - 3]. Results. The ERSPC data are based on a core age group of 162 387 men, aged 55-69 years, who were identified through population registries in seven European countries. Men were randomized between a screening group that received screening at an average of once every four years and a control group. After a median follow-up of nine years, a reduction in the rate of death from PC by 20% was shown which increased to 31% after adjusting for non-compliance and contamination. Overdetection and subsequent overtreatment (with a number needed to treat (NNT) of 48) are considered to be the major down sides of screening. The recently published 14-year results have shown that these down sides strongly depend on the duration of follow-up. In response to the outcomes of the ERSPC, several points of discussion have been brought up by various authors concerning the usefulness of screening considering benefits, harms and costs, the methodology of the ERSPC and the interpretation of its outcomes. Important issues to address regarding PC screening are addressed. Conclusions . This paper sheds a light on the controversial points of the ERSPC as well as on the priority issues of PC screening. On July 2, 2010 the Swedish section of ERSPC (Göteborg screening trial) published their results with a median follow-up of 14 years. With longer follow-up the data confirm the trend seen in improvement of PC mortality and suggest much more favorable future outcomes also with respect to the NNT to prevent one PC death. [ABSTRACT FROM AUTHOR]

The aim of this paper was systematically to evaluate the caries-preventive effect of professional fluoride varnish treatments. A search of the literature for articles published between 1966 and August 2003 was carried out in electronic databases, reference lists of articles, and selected textbooks in accordance with the strategy of the Swedish Council on Technology Assessment in Health Care. Out of 302 identified papers, 24 randomized and controlled clinical trials comparing fluoride varnish with placebo, no active treatment or other fluoride preventive regimens of at least 2 years' study duration were included. The trials that met the inclusion criteria were assessed independently and systematically by at least two reviewers and scored from A to C according to predetermined criteria for methodology and performance. The main outcome measure was the preventive fraction expressed as a percentage. The results displayed limited evidence (evidence level 3) for the caries preventive effect of topical applications of fluoride varnishes in permanent teeth. The average prevented fraction was 30% (0-69%) when compared with untreated controls. Inconclusive evidence (evidence level 4) was found for fluoride varnish treatment in the primary dentition and in adults. This systematic review reinforces the need for future clinical research of high quality, incorporating modern concepts of clinical performance and evaluation to assess dental caries control using professional fluoride varnish. [ABSTRACT FROM AUTHOR]

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on chemotherapy in the treatment of gastric cancer is based on 153 scientific papers including one meta-analysis, 18 reviews, 60 randomised studies and 57 prospective studies. The trials consist of 12 367 patients. The conclusions reached can be summarized into the following points: •A meta-analysis of 21 randomised adjuvant studies revealed a statistically significant survival benefit. The Odds Ratio (OR) is 0.84 (95% confidence interval, 95% CI, 0.74-0.96). However, by analysing Western world and Asian studies separately, a statistically significant difference can be noticed; the Western world studies showed an OR of 0.96 (95% CI 0.83-1.12) and the Asian an OR of 0.58 (95% CI 0.44-0.76). The cause of this difference is not apparent. There is not sufficient evidence to recommend adjuvant chemotherapy as routine treatment in the Western world. •Preoperative chemotherapy given to patients with non-resectable tumours or locally advanced potentially resectable tumours has achieved resectability rates of 40-100% and potentially curative resections in 37-80%. One out of two randomised studies showed a significant survival benefit, but reported data are not convincing. Experimental data in favour of preoperative therapy has not yet been confirmed in randomised clinical studies. Therapy is only justified in controlled clinical trials. •Published studies on the use of intraperitoneal chemotherapy are few and not conclusive regarding the efficiency and safety. This method of drug administration is, accordingly, justified only in controlled clinical trials. •In advanced gastric cancer, phase II studies have indicated better response rates using drug combinations than using single drug regimens, differences that have not, however, been convincingly demonstrated in randomised studies. No firm conclusions can be drawn regarding the superiority for any of the studied drug combinations with respect to response or survival gain. •A statistically significant survival benefit has been shown in trials comparing drug combinations with a best supportive care arm in the treatment of advanced gastric cancer. However, the number of included patients is small. The median survival benefit in advanced disease is in the range of three to nine months. •The use of chemotherapy in advanced gastric cancer is justified in selected patients, e.g. in younger patients in good performance status, low tumour burden and no other serious medical condition after adequate information of potential gains and risks. •The influence of chemotherapy on quality of life in advanced gastric cancer has been reported in only a few studies. It appears that about 50% of the patients have a clinically relevant relief of tumour-related symptoms and thereby improved quality of life. In one study, quality-adjusted survival was estimated to a median of six months in the treated patients compared with two months in the controls. •The quality of the literature addressing chemotherapy for gastric cancer is frequently poor with few properly designed randomised trials. In a number of randomised multi-centre adjuvant studies the inclusions rates are remarkably low, which reduces the scientific value of the studies. [ABSTRACT FROM AUTHOR]

It is common practice to undertake interim analyses of accumulating survival data in a cancer clinical trial while patient entry and/or follow-up is still in progress. The purpose of making an interim analysis is to stop the trial if a convincing treatment difference can be demonstrated. The main problem with repeated significance tests is that the more often one analyses accumulating data, the greater the probability of eventually obtaining a significant result, p<0.05 say, even when there is in reality no treatment difference. To allow for repeated testing one must therefore choose a more stringent nominal significance level as a criterion for stopping the trial. Repeated significance tests are normally applied at equally spaced intervals, and the maximum number of tests is decided in advance. This paper presents and compares the properties of two simple and commonly applied strategies for undertaking interim analyses of accumulating survival data. [ABSTRACT FROM AUTHOR]

The aim of this systematic review was to evaluate the effectiveness of conservative different therapeutic modalities for temporomandibular disorders (TMD) pain. An electronic systematic search was conducted in the MEDLINE (PubMed) database to identify the randomized clinical trials (RCTs) published between 2001 and 2021. The following, simple or multiple conjunctions, search keywords were selected: TMD pain, TMD management or conservative treatment or treatment strategies and TMD pain, therapeutic modalities or interventions and TMD. Studies included must have patients older than 18 years, with painful TMD, which diagnosis was performed by Research Diagnostic Criteria for TMD or Diagnostic Criteria for TMD. Outcome variables were pain relief and post treatment pain intensity reduction. Data were analysed with non-parametric tests and the level of significance was set at p<.05. Out of 1599 articles obtained, 28 RCTs fulfilled all selection criteria and were included. The results of this study show that there was a significant decrease in short-term post-treatment TMD pain with the use of occlusal splint alone or in combination with other therapeutic modalities when compared with the control group. Statistically significant differences were also detected between laser and photobiomodulation group and the control, in short-term treatment TMD-related pain. The primary findings of the present systematic review showed that the occlusal splint alone or combined with other therapeutic intervention presented positive effect on short-term TMD pain reduction. Secondary outcome suggests that laser and photobiomodulation therapy had, also, a significant role in short term pain relief. [ABSTRACT FROM AUTHOR]

The article reports that Clinical Pharmacogenetics Implementation Consortium updated best practice guidelines in 2018 for 5-FU and capecitabine dose optimization. Topics include examines CPIC recommended that the four common DPYD genetic variants known to affect DPD enzyme activity should be incorporated as part of a DPD screening program.

Psychological distress may be present among patients who are considering enrollment in phase 1 cancer trials, as they have advanced cancer and no documented treatment options remain. However, the prevalence of psychological distress has not been previously investigated in larger cohorts. In complex phase 1 cancer trials, it is important to ensure adequate understanding of the study premises, such as the undocumented effects and the risk of adverse events. In a prospective study, patients completed questionnaires at two time points. We investigated psychological distress, measured as stress, anxiety, and depression, among patients at their first visit to the phase 1 unit (N = 229). Further, we investigated the understanding of trial information among patients who were enrolled in a phase 1 cancer trial (N = 57). We enrolled 75% of 307 eligible patients. We found a lower mean score of stress in our population compared to population norms, while the mean scores of anxiety and depression were higher. A total of 9% showed moderate to severe symptoms of anxiety and 11% showed moderate to severe symptoms of depression, which indicates higher levels than cancer patients in general. A total of 46 (81% of enrolled patients) completed questionnaires on trial information and consent. The understanding of the information on phase 1 cancer trials in these patients was slightly lower than the level reported for cancer trials in general. Some aspects relating to purpose, benefit, and additional risks were understood by fewer than half of the patients. Our results suggest that distress is not as prevalent in the population of patients referred to phase 1 cancer trials as in the general cancer population. Although patients' understanding of trial information was reasonable, some aspects of complex phase 1 cancer trials were not easily understood by enrolled patients. [ABSTRACT FROM AUTHOR]

In clinical practice, interruption of treatment may not result in immediate cessation of disease control, and some patients even experience sustained treatment response following treatment interruption. This post hoc analysis of UNCOVER-1 and -2 Phase 3 clinical trials characterized the time to loss of treatment response in patients with psoriasis who responded to ixekizumab through a 12-week treatment period, and who were then re-randomized to placebo for the following 48 weeks. For those with static Physician Global Assessment [sPGA]0/1 and Psoriasis Area and Severity Index [PASI]90 at Week 12, the median time to loss of PASI90 was 16.1 weeks (95% confidence interval 12.7-16.4). For those with PASI100 at Week 12, the median time to loss of PASI100 was 12.1 weeks (95% confidence interval 9.0-13.0). A small subset of patients maintained high levels of disease control through Week 60. This study adds to the growing body of evidence on sustained treatment response following treatment interruption. [ABSTRACT FROM AUTHOR]

Chronic pruritus is a common symptom, associated with several severe medical conditions, great psychological burden, and reduced quality of life. It also poses socio-economic challenges concerning patients' work loss and healthcare costs. In Germany, medical rehabilitation programmes represent an integral part of the medical care of patients with chronic inflammatory skin diseases. However, such programmes play only a rudimentary role in the treatment of other dermatological diseases, such as dermatological oncology, genetic skin diseases, and chronic pruritus. Therefore, a specific antipruritic dermatological rehabilitation programme was developed in cooperation between the Department of Dermatology of the Medical Rehabilitation Center Bad Bentheim and the Center for Chronic Pruritus of the University Hospital of Muenster, Germany. This prospective study compared short-term patient-reported outcomes (n = 121) at the beginning and end of the rehabilitation programme. The majority of subjects had chronic pruritus on primary diseased, inflamed skin. Significant improvements in pruritus intensity (p ≤ 0.001), quality of life (p ≤ 0.001), anxiety symptoms (p ≤ 0.001) and depression (p ≤ 0.001), as well as an overall patientrelevant benefit (Patient Benefit Index 2.6 ± 1.06) and treatment-related patients' satisfaction, were shown. This suggests that implementation of this standardized rehabilitation programme for treatment of patients with chronic pruritus was successful. [ABSTRACT FROM AUTHOR]

Background and purpose — Tourniquet is widely used in orthopedic surgery to reduce intraoperative bleeding and improve visualization. We evaluated the effect of tourniquet application on peri- and postoperative cefuroxime concentrations in subcutaneous tissue, skeletal muscle, calcaneal cancellous bone, and plasma. The primary endpoint was the time for which the free cefuroxime concentration was maintained above the clinical breakpoint minimal inhibitory concentration (T > MIC) for Staphylococcus aureus (4 µg/mL). Patients and methods — 10 patients scheduled for hallux valgus or hallux rigidus surgery were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in subcutaneous tissue, skeletal muscle, and calcaneal cancellous bone. A tourniquet was applied on the thigh of the leg scheduled for surgery (tourniquet duration time [range]: 65 minutes [58–77]). Cefuroxime (1.5 g) was administered intravenously 15 minutes prior to tourniquet inflation, followed by a second dose 6 hours later. Dialysates and venous blood samples were collected for 12 hours. Results — A cefuroxime concentration of 4 µg/mL was reached within 23 minutes in all compartments and patients. For cefuroxime the T > MIC (4 µg/mL) ranged between 4.8 and 5.4 hours across compartments, with similar results for the tourniquet and non-tourniquet leg. Comparable T > MIC and penetration ratios were found for the first and second dosing intervals. Interpretation — Administration of cefuroxime (1.5 g) 15 minutes prior to tourniquet inflation is safe in order to achieve tissue concentrations above 4 µg/mL throughout surgery. A tourniquet application time of approximately 1 hour did not affect the cefuroxime tissue penetration in the following dosing interval. [ABSTRACT FROM AUTHOR]

Objectives. This in vitro study aimed to analyze the effect of TiF4 compared to NaF varnishes and solutions, to protect against dentin erosion associated with abrasion. Materials and methods. Bovine dentin specimens were pre-treated with NaF-Duraphat (2.26% F), NaF/CaF2-Duofluorid (5.63% F), experimental-NaF (2.45% F), experimental-TiF4 (2.45% F) and placebo varnishes; NaF (2.26% F) and TiF4 (2.45% F) solutions. Controls remained untreated. The erosive pH cycling was performed using a soft drink (pH 2.6) 4 × 90 s/day and the toothbrushing-abrasion 2 × 10 s/day, in vitro for 5 days. Between the challenges, the specimens were exposed to artificial saliva. Dentin tissue loss was measured profilometrically (μm). Results. ANOVA/Tukey's test showed that all fluoridated varnishes (Duraphat, 7.5 ± 1.1; Duofluorid, 6.8 ± 1.1; NaF, 7.2 ± 1.9; TiF4, 6.5 ± 1.0) were able to significantly reduce dentin tissue loss (40.7% reduction compared to control) when compared to placebo varnish (11.2 ± 1.3), control (11.8 ± 1.7) and fluoridated (NaF, 9.9 ± 1.8; TiF4, 10.3 ± 2.1) solutions ( p < 0.0001), which in turn did not significantly differ from each other. Conclusion. All fluoridated varnishes, but not the solutions, had a similar performance and a good potential to reduce dentin tissue loss under mild erosive and abrasive conditions in vitro. Risk patients for erosion and abrasion, especially those with exposed dentin, should benefit from this clinical preventive measure. Further research has to confirm this promising result in the clinical situation. [ABSTRACT FROM AUTHOR]

Delamination or fracture of composite veneers can occur as a result of improper design of the fiber-reinforced composite (FRC) framework. This in vitro study tested the repair bond strength of restorative composite to aged FRC. The substrate was multiphase polymer matrix FRC (everStick) aged by boiling for 8 h and storing at 37 degrees C in water for 6 weeks. The aged substrate surfaces were wet-ground flat with 1200-grit silicon carbide paper and subjected randomly to 5 different surface treatments: 1) An adhesion primer (Composite Activator) and resin (CA), 2) Silane (EspeSil) and resin (SIL-MP), 3) Silane, adhesive primer, and resin (Clearfil Repair) (CF), 4) Air particle-abrading (CoJet), silane, and resin (CJ-SIL-MP), 5) Resin (Scotchbond Multipurpose Resin) only as control (MP). Restorative composite resin (Z250) was added to the substrate in 2 mm layer increments and light-cured. Subsequently, every surface treatment group was divided into 2 subgroups of 12 specimens each. The specimens were either 48 h water-stored or thermocycled (6000 x 5-55 degrees C). The shear bond strengths of composite resin to FRC were measured at a crosshead speed of 1.0 mm/min. The data were analyzed by ANOVA for factors 'treatment type' and 'storage condition'; Tukey's post-hoc tests and Weibull analysis were performed. ANOVA showed a significant difference as a function of surface treatment (P<0.05) and storage condition (P<0.05). The CJ-SIL-MP group showed highest bond strength and Weibull modulus after thermocycling. Repair of multiphase polymer matrix FRC may show reliable bond strength when silane treatment is used along with air-particle abrading. [ABSTRACT FROM AUTHOR]

To compare the efficacy and safety of inferior alveolar nerve blocks (IANB) with additional buccal infiltration (standard technique) and of buccal and lingual anaesthetic infiltration (experimental technique) for lower third molar (L3M) extractions. A randomised, double-blind clinical trial involving 129 L3M extractions was conducted. In the IANB group, an IANB was performed using the conventional approach, followed by a buccal injection in the extraction area. In the infiltration group (INF), an infiltration was performed in the buccal and lingual areas of the lower second molar. A 4% articaine solution was employed in all cases. The main outcome variable was anaesthetic efficacy. Other variables like intraoperative and postoperative pain, onset time and adverse events were also recorded. Descriptive and bivariate analyses of the data were made. 120 patients were randomised. The IANB group showed significantly higher anaesthetic efficacy than the INF group (64.4 vs. 45.8%) (odds ratio = 0.47; 95% confidence interval = 0.22–0.97; p = 0.042). No complications were observed. IANB with additional buccal infiltration is more suitable than the experimental technique for achieving adequate analgesia in L3M extractions. Moreover, the standard method is safe and provides a shorter onset time and lower initial postoperative pain levels. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of different local anaesthetic techniques in pain, disruptive behaviour and anxiety in children´s dental treatment.Material and methods: This was a randomised and parallel clinical trial. The sample consisted of 105 children (5-8 years old) that were divided into three groups (n = 35) according to the anaesthetic technique: conventional anaesthesia (CA); vibrational anaesthesia (VBA); computer-controlled local anaesthesia delivery (CCLAD). The outcomes were self-perception of pain (Wong-Baker Faces Pain Rating Scale - WBF; Numerical Rating Scale - NRS); disruptive behaviour (Face, Legg, Activity, Cry, Consolability Scale - FLACC); anxiety (Corah's Dental Anxiety Scale; modified Venham Picture test - VPTm) and physiological parameters (blood pressure - systolic - SBP and diastolic - DBP; heart rate - HR; oxygen saturation - SpO2; respiratory rate - RR). Data were statistically analysed with Kruskall-Wallis test and ANOVA for repeated measures with Tukey post hoc test (α = 0.05).Results: All the patients exhibited the same level of dental anxiety at baseline (Corah's Dental Anxiety Scale). There was no difference in self-perception pain, irrespective the evaluation tool used (WBF - p = .864; VAS - p = .761). No differences were detected in disruptive behaviour (FLACC - p = .318); anxiety (VPTm - p = .274); blood pressure (SBP - p = .239; DBP - p = .512); heart rate (p = .728); oxygen saturation (p = .348) and respiratory rate (p = .238) between anaesthetic techniques.Conclusion: Different anaesthetic dental local techniques do not affect the levels of pain, disruptive behaviour, anxiety and physiological parameters in children aged 5-8 years old. [ABSTRACT FROM AUTHOR]

The term skin fragility disorders describes a group of conditions in which the structural integrity of the skin is compromised and its resistance to external shear forces diminished. Skin fragility can have different causes, ranging from genetic variations to inflammatory or physical phenomena. The genetic skin fragility disorders, collectively called epidermolysis bullosa, serve as a paradigm for the study of causes and mechanisms of skin fragility. Recent biomedical research has revealed substantial genetic heterogeneity of the epidermolysis bullosa group, delivered ample new knowledge on its pathophysiology, and facilitated the design of evidence-based therapeutic strategies. The therapy development process extends from in vitro testing to preclinical validation in animal models, and clinical trials. This article reviews different approaches to curative and symptom-relief therapies, and appraises their status and perspectives for clinical implementation. [ABSTRACT FROM AUTHOR]

The article focuses on the need of questionnaires for itching that should consider both the patient's and the doctor's perspectives as well as the need to gather important medical information. It mentions patient-doctor relationship and indispensable for clinical trials, investigations into quality of life, psychological studies and pathophysiological research. It also mentions itch is associated with pain, burning tingling, tickling, prickling, tightness or stinging.

Impaired sleep due to nocturnal pruritus is a common symptom in patients with chronic pruritus. How ever, there is no standardized, simplified instrument for assessing sleep-related problems in patients with chronic pruritus. After a literature search, we conducted 50 interviews with patients with chronic pruritus and tested 12 items most frequently used in routine sleep questionnaires. Afterwards, 2 sleep assessment questionnaires (Pittsburgh Sleep Quality Index; Regensburg Insomnia Scale) were selected for use in 88 patients with chronic pruritus with sleep impairment due to pruritus. They were completed twice; once before optimizing their individual pruritus therapy and once again after 4 weeks. During the latter survey, 21 patients reported that pruritus no longer negatively affected their sleep. These patients also achieved a significant improvement in their sleeping behaviour in the Regensburg Insomnia Scale. Therefore, the Regensburg Insomnia Scale appears to be well-suited to assessing sleep impairment in patients with chronic pruritus. [ABSTRACT FROM AUTHOR]

The article offers information about a study which aims to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Information on the collection of data from several hospitals and the analysis of drug survival using Kaplan– Meier survival curves as well as the treatment of secukinumab, which is the first interleukin-17 inhibitor registered for treatment of plaque psoriasis, is presented.

Objective: This review aimed to investigate the feasibility of immediate implant placement in infected extraction sockets.Material and Methods: We performed electronic and manual searches up to March 2017 to obtain data from randomized controlled trials (RCTs) and nonrandomized controlled clinical trials (CCTs). Using a fixed-effects model to assess the difference in survival rate (primary outcome), we evaluated the risk difference for immediate implant placement in infected and non-infected sites. We estimated the weighted mean differences (WMDs) of the change in marginal bone loss (MBL), probing depth (PD), modified bleeding index (mBI), marginal gingival level (MGL) and width of keratinized gingiva (WKG) at baseline and latest follow-up.Results: In total, five studies (0 RCT, five CCTs) were included in the systematic review and three studies were included in the meta-analysis. The risk difference for immediate implant placement in an infected extraction socket compared with that in a non-infected socket was -0.02. WMDs for MBL, PD, mBI, MGL and WKG between the two groups were 0.32, 0.12, 0.07, -0.06, 0.20 and 0.51, respectively. No statistical differences were observed between the two groups, except for the change in WKG.Conclusions: Implants can be placed in infected extraction sockets after thorough socket debridement. For aesthetics, WKG should be considered when performing immediate implant placement in infected sites. [ABSTRACT FROM AUTHOR]

Objective: To determine if the use of orthopaedic appliances in growing patients applied to correct Class II and III malocclusion is related to the development of temporomandibular disorders (TMD).Material and Methods: A systematic review was conducted between 1960 and July 2017, based on electronic databases: PubMed, Cochrane Library, Embase, Medline, Scopus, EBSCOhost, Scielo, Lilacs and Bireme. Controlled clinical trials (CCTs) and randomized controlled trials (RCTs) were identified. The articles were selected and analyzed by two authors independently. The quality of the evidence was determined according to the guidelines of the Cochrane Risk Bias Assessment Tool and the Cochrane Quality Study Guide.Results: Seven articles were included, four CCTs and three RCTs. The studies were grouped according to malocclusion treatment in (a) class II appliances (n = 4) and (b) class III appliances (n = 3). The quality of evidence was low due to the high risk of bias, independent of the association reported. All studies concluded that the use of orthopaedic appliances would not contribute to the development of TMD.Conclusions: The quality of evidence available is insufficient to establish definitive conclusions, since the studies were very heterogeneous and presented a high risk of bias. However, it is suggested that the use of orthopaedic appliances to correct class II and III malocclusion in growing patients would not be considered as a risk factor for the development of TMD. High-quality RCTs are required to draw any definitive conclusions. [ABSTRACT FROM AUTHOR]

Background: Over the past 40 years the Danish Breast Cancer Cooperative Group (DBCG) has made significant contributions to improve outcome and to make treatment of patients with early breast cancer more tolerable through nationwide and international trials evaluating loco-regional and systemic treatments. These trials have been instrumental to establish standards for the treatment of early breast cancer. Methods: The DBCG 82 trials had a global impact by documenting that the significant gain in locoregional recurrence from postmastectomy radiation added to systemic therapy was associated with a reduction in distant recurrence and mortality in high-risk pre- and postmenopausal patients. The DBCG trials comparing breast conserving surgery and radiotherapy with mastectomy and more recently the trial of internal mammary node irradiation also had a major impact of practice. The trials initiated by the DBCG 40 years ago on tamoxifen and cyclophosphamide based chemotherapy became instrumental for the development of adjuvant systemic therapy not only due to their positive results but by sharing these important data with other members of the Early Breast Cancer Trialist’ Collaborative Group (EBCTCG). Trials from the DBCG have also been important for highlighting the relative importance of anthracyclines and taxanes in the adjuvant setting. Furthermore, DBCG has made a major contribution to the development of aromatase inhibitors and targeted adjuvant treatment for human epidermal growth factor receptor 2 positive breast cancers. Results: The substantial impact of these treatment improvements is illustrated by a 46.7% 10-year overall survival of early breast cancer patients treated in 1978–1987 compared to 71.5% for patients treated 2008–2012. Conclusions: The trials conducted and implemented by the DBCG appear to have a major impact on the substantial survival improvements in breast cancer. [ABSTRACT FROM AUTHOR]

Background and Objective: To date, various drugs as host modulating agents had been suggested as adjunctive treatment modality in the therapy of chronic periodontal disease. In this study, the anti-inflammatory effect of subgingivally delivered nanostructured doxycycline gel (nDOX) was evaluated and compared to conventional doxycycline gel (DOX) used as adjunct to scaling and root planning (SRP) in the treatment of moderate chronic periodontitis to reduce probing pocket depth.Material and Methods: Nanostructured doxycycline gel (nDOX) was prepared using spray-drying technique with chitosan (CH) as a matrix polymer, followed by dispersion in polyvinyl alcohol (PVA). The deepest periodontal pocket in 45 patients suffering from moderate chronic periodontitis was selected. The patients were divided into three groups following scaling and root planning (SRP); group I: SRP + nDOX, group II: SRP + DOX and group III: SRP + placeboCH. Plaque Index (PI), Gingival Index (GI), pocket depth (PD) and clinical attachment level(CAL), as well as ginigival crevicular fluid levels of (GCF) IL-6 and TNF-α were assessed at baseline, 1 and 3 months following local drug application.Results: Group I showed significant reduction in probing depth and attachment gain compared with group II and III at one and three months period. The inflammatory mediators levels were significantly reduced in all treatment groups at one-month period. Except for group I, the reduced values were observed at three-month period.Conclusion: The results suggest that treatment with nDOX gel as an adjunct to SRP had anti-inflammatory effect by improving both clinical parameters and inflammatory markers up to three months period. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this pilot study was to compare the effectiveness of two different methods of debridement on maintaining and improving peri-implant soft tissue health over a period of 12 months.Materials and Methods: Twenty adult patients (25 implants) were enrolled in a randomized, single-blinded, parallel group clinical trial. All implants included showed no signs of pathologic bone loss. Patients were scheduled to be reviewed every 3 months over a 12 months period. Nine patients (15 implants) were randomly allocated to a test group and treated with a low abrasive air polishing powder (Air-Flow® Perio, EMS) (AFP) and another nine (10 implants) to a control group and treated with titanium curettes (TC). Peri-implant crevicular fluid samples were analyzed to quantitatively measure the concentration of six interleukins (IL-6, IL-8, IL-1β, TNF, IL-10 and IL-12). A multilevel analysis was used to test the comparison between the two treatments. The same analysis was used to study the relationship between clinical parameters and cytokines while controlling for confounding factors.Results: There was no significant difference in bleeding on probing (BOP) between the two treatment methods (p = .35). Both debridement techniques resulted in a similar reduction of BOP (40.04% and 39.93%). IL-6 was the only cytokine of the six investigated that demonstrated a correlation with a clinical parameter (BOP) (p = .05).Conclusions: Both treatment methods were proven to be effective in reducing peri-implant inflammation and preventing further disease progression. Some cytokines may act as markers for peri-implant disease as the present study showed a significant relationship between IL-6 and BOP. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the intensity and duration of postoperative pain after the removal of root canal filling material in retreatment procedures of upper incisor teeth with chronic apical periodontitis, using different techniques.Materials and Methods: One hundred and thirty-five patients requiring retreatment of upper incisor teeth with chronic apical periodontitis were included in the study. The patients were assigned to three groups of 45 patients, according to the method used to remove old canal filling material. In group 1, canal filling material was removed using hand files. In group 2, the canal filling material was removed with ProTaper universal retreatment (PTUR) instruments. In group 3, Reciproc instruments were used to remove canal filling material. Teeth were then medicated with calcium hydroxide and sealed using temporary filling material. The presence of postoperative pain was assessed after 6, 12, 24, 48 and 72 h, 7 days, and finally after 10 days.Results: In all time intervals, except for 72 h, 7 days and 10 days, group 1 participants reported more intense postoperative pain than those in groups 2 and 3 (p = 0.02). In all time intervals, there was no difference in the pain scores between groups 2 and 3 (p = 0.08). In all groups, the intensity of postoperative pain decreased over time. The required time to remove canal filling material was less for the Reciproc group compared to the hand and ProTaper retreatment groups (p = 0.032).Conclusions: Hand files caused greater postoperative pain after non-surgical endodontic retreatment (NSER) of upper incisor teeth with chronic apical periodontitis compared to the ProTaper retreatment and Reciproc files. [ABSTRACT FROM AUTHOR]

It is unclear which quality of life instruments have thus far been used in eczema trials. Therefore, we aimed to identify these instruments. We searched the Global Resource of Eczema Trials (GREAT) database for reports of randomized controlled trials. Information on patientreported outcomes, particularly quality of life, was extracted from eligible studies. Two-hundred and eightyseven full texts reporting on 303 trials and 72 abstracts were included. Of the 303 studies, 63 (20.8%) assessed quality of life and used 18 named and 4 unnamed instruments. The Dermatology Life Quality Index (DLQI), the Children's Dermatology Life Quality Index (CDLQI), the Infants' Dermatitis Quality of Life Index (IDQOL), and the Dermatitis Family Impact (DFI) were the most common measures in adults, children, infants, and caregivers, respectively. In conclusion, only about one fifth of eczema trials include a quality of life measure as outcome. Many different instruments are used, limiting the possibilities of comparing and synthesising individual trials' findings. [ABSTRACT FROM AUTHOR]

Objective: Polypeptide growth factors of platelet rich fibrin (PRF) have the potential to regenerate periodontal tissues. Osteoinductive property of demineralized freeze-dried bone allograft (DFDBA) has been successfully utilized in periodontal regeneration. The aim of the present randomized, split mouth, clinical trial was to determine the additive effects of PRF with a DFDBA in the treatment of human intrabony periodontal defects.Materials and Methods: Sixty interproximal infrabony defects in 30 healthy, non-smoker patients diagnosed with chronic periodontitis were randomly assigned to PRF/DFDBA group or the DFDBA/saline. Clinical [pocket depth (PD), clinical attachment level (CAL) and gingival recession (REC)] and radiographic (bone fill, defect resolution and alveolar crest resorption) measurements were made at baseline and at a 12-month evaluation.Results: Compared with baseline, 12-month results indicated that both treatment modalities resulted in significant changes in all clinical and radiographic parameters. However, the PRP/DFDBA group exhibited statistically significantly greater changes compared with the DFDBA/saline group in PD (4.15 ± 0.84 vs 3.60 ± 0.51 mm), CAL (3.73 ± 0.74 vs 2.61 ± 0.68 mm), REC (0.47 ± 0.56 vs 1.00 ± 0.61 mm), bone fill (3.50 ± 0.67 vs 2.49 ± 0.64 mm) and defect resolution (3.73 ± 0.63 vs 2.75 ± 0.57 mm).Conclusion: Observations indicate that a combination of PRF and DFDBA is more effective than DFDBA with saline for the treatment of infrabony periodontal defects. [ABSTRACT FROM AUTHOR]

Background.Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. Material and methods.Patients with resectable colon cancer fulfilling the following criteria were offered inclusion; Histopathological verification of adenocarcinoma, T3 tumor on CT scan with extramural tumor invasion > 5 mm or T4 tumor, age ≥ 18 years, PS ≤ 2, adequate hematology, and informed consent. Patients with KRAS, BRAF or PIK3CA mutation or unknown mutational status received three cycles of capecitabine 2000 mg/m2days 1-14 q3w and oxaliplatin 130 mg iv day 1 q3w. Wild-type patients received the same chemotherapy supplemented with panitumumab 9 mg/kg iv q3w. After the operation, patients fulfilling the international criteria for adjuvant chemotherapy, i.e. high-risk stage II and III patients, received five cycles of the same chemotherapy without panitumumab. Patients not fulfilling the criteria were offered follow-up only. The primary endpoint was the fraction of patients not fulfilling the criteria for adjuvant chemotherapy (converted patients). Secondary endpoints were recurrence rate, disease-free survival (DFS), and toxicity. Results.The study included 77 patients. The conversion rate was 42% in the wild-type group compared to 51% in patients with a mutation. The cumulative recurrence rate in converted versus unconverted patients was 6% versus 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). Conclusion.Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted. [ABSTRACT FROM PUBLISHER]

Background.Response assessment after stereotactic ablative body radiotherapy (SABR) in lung can be confounded by radiation-induced inflammation, fibrosis and subsequent alteration of tumour motion. The purpose of this prospective pilot study was to evaluate the utility of four-dimensional (4D) FDG-PET/CT for post-SABR tumour and normal lung response assessment in pulmonary oligometastases. Material and methods.Patients enrolled from February 2010 to December 2011 in this prospective ethics approved study had 1–2 pulmonary metastases on staging FDG-PET. Serial contemporaneous 3D and 4D FDG-PET/CT scans were performed at baseline, 14 days and 70 days after a single fraction of 26 Gy SABR. Tumour response was evaluated in 3D and 4D using SUVmax, RECIST and PERCIST criteria. Normal lung radiotoxicity was evaluated using SUVmean within 0–2 Gy, 2–5 Gy, 5–10 Gy, 10–20 Gy and 20 + Gy isodose volumes. Results.In total, 17 patients were enrolled of which seven were ineligible due to interval progression from staging PET to baseline 4D-PET. The mean time between scans was 62 days. At a median follow-up of 16 months, 10 patients with 13 metastases received SABR, with no patient having local progression. The vector of tumour motion was larger in patients with discordant 3D and 4D PET PERCIST response (p < 0.01), with a mean (± SEM) motion of 10.5 mm (± 0.96 mm) versus 6.14 mm (± 0.81 mm) in those patients with concordant 3D and 4D response. Surrounding normal lung FDG uptake at 70 days was strongly correlated to delivered radiation dose (r2= 0.99, p < 0.01), with significant elevations across all dose levels (p ≤ 0.05), except the < 2 Gy volume (p = 0.30). Conclusions.We demonstrate high rates of interval progression between staging PET scans in patients with oligometastases. We found that tumour response on conventional 3D PET is not concordant with 4D PET for tumours with large motion. Normal lung metabolic uptake is strongly dose dependent after SABR, a novel finding that should be further validated. [ABSTRACT FROM AUTHOR]

Background.Presentation of long term results of a phase II multicenter Nordic trial of medically inoperable stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Material and methods.We report the extended outcome, focusing on long-term effects, of a prospective cohort of 57 evaluable patients with peripherally located T1N0M0 (72%) and T2N0M0 (28%) NSCLC, treated with SBRT 15 Gy × 3, prescribed to the 67% isodose line encompassing the PTV. The patients were inoperable due to chronic obstructive pulmonary disease (65%), cardiovascular disease (25%) or other illnesses (3%) or refused surgery (7%). Median Karnofsky score pre-treatment was 80% (70–100%). Late effects were defined as occurring > 36 months. Results.Thirty-eight patients (67%) were relapse free during their entire follow-up. Local control rate at four and five years were 79% (CI 95% 64–95%) and local relapses occurred at 10–76 months post-treatment. Seven local failures were noted, four occurring ≤ 36 months (all T2a-tumors; two isolated and two in combination with out-of-field relapses) and three occurring > 36 months (T1b-tumors n = 3). Thirteen patients had out-of-field failure only as first presentation of recurrence. Overall survival rate and lung cancer-specific survival rate at five years were 30% and 74%, respectively. Toxicity throughout the entire observation period was acceptable without any grade 5 toxicities. Seventeen grade 3–4 toxicities were noted, three presenting > 36 months (rib fracture, dyspnea and ventricle tachycardia). Median follow-up was 41.5 months (3.4–113.0) for the entire cohort and 59.3 months (36.4–113.0) for the 34 patients (60%) with a follow-up of > 36 months. Conclusion.Throughout the observation period local control was excellent and toxicity limited with no increase in late presenting local relapses or late treatment-related morbidity. This further supports SBRT as an efficient local treatment modality even in a medically impaired patient cohort. [ABSTRACT FROM AUTHOR]

Objective. The benefit of full-mouth disinfection (FDIS) over traditional scaling and root planing (SRP) in the treatment of chronic, destructive periodontitis remains equivocal and it is not known whether the use of adjunctive antibiotics may enhance the effect of FDIS. Therefore, the aim of this study was to evaluate the effect of conventional SRP completed over 21 days or 1-day FDIS, with or without systemically delivered adjunctive metronidazole (MET) on the presence of P. gingivalis and T. forsythia after 3 and 12 months. Materials and methods. One hundred and eighty-four patients with moderate-to-severe periodontitis were randomly allocated to one of four treatment groups; (1) FDIS+MET; (2) FDIS+placebo; (3) SRP+MET; (4) SRP+placebo. Prior to treatment, pooled subgingival samples were obtained from the five deepest pockets. The same sites were sampled again 3 and 12 months after treatment. All samples were analyzed for P. gingivalis and T. forsythia by PCR, whereas A. actinomycetemcomitans and other bacteria were identified by culture techniques. Results. At baseline, 47% of the samples were positive for P. gingivalis, while almost all samples were positive for T. forsythia. The occurrence of P. gingivalis and T. forsythia was significantly reduced at 3 and 12 months after treatment in the FDIS+MET group, but not in the other treatment groups. Conclusion. FDIS+MET had a significant effect in patients with P. gingivalis and T. forsythia, resulting in a significant reduction in number of patients where these micro-organisms could be detected at 3 and 12 months post-therapy. [ABSTRACT FROM AUTHOR]

Background. For stage II and III head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy alone, loco-regional recurrence is the main cause of treatment failure. Strategies to improve loco-regional control should not be at the expense of increased late normal tissue toxicity. We investigated dose-intensified hypofractionated intensity-modulated radiotherapy (IMRT) with synchronous cetuximab. Material and methods. In a phase I/II trial, 27 patients with stage III or high risk stage II HNSCC were recruited. They received three dose level simultaneous integrated boost IMRT, 62.5 Gy in 25 daily fractions to planning target volume one over five weeks with synchronous cetuximab. The primary endpoint was acute toxicity. Secondary endpoints included: late toxicity and quality of life; loco-regional control, cause-specific and overall survival. Results. Radiotherapy was completed by 26/27 patients; for one (4%) the final fraction was omitted due to skin toxicity. All cycles of cetuximab were received by 23/27 patients. Grade 3 acute toxicities included: pain (81%), oral mucositis (78%) and dysphagia (41%). There were few grade 3 physician-recorded late toxicities, including: pain (11%), problems with teeth (8%) and weight loss (4%). At 12 months, only one (4%) patient required a feeding tube, inserted prior to treatment due to dysphagia. The maximal/peak rates of patient-reported late toxicities included: severe pain (11%), any dry mouth (89%) and swallowing dysfunction that required a soft/liquid diet (23%). At 12 months, all quality of life and most symptoms mean scores had resolved to baseline or were only a little worse; dry mouth, sticky saliva and dentition scores remained very much worse. At a median follow-up of 47 months, there were five (18.5%) loco-regional recurrences and the overall cause-specific survival was 79% (95% CI 53-92). Conclusions. This regimen is safe with acceptable acute toxicity, low rates of late toxicity and impact on quality of life at 12 months following treatment. Further evaluation is recommended. [ABSTRACT FROM AUTHOR]