Tumor-agnostic plasma assay for circulating tumor DNA detects minimal residual disease and predicts outcome in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing. PATIENTS AND METHODS: A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, ß = 0.9). RESULTS: We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011). CONCLUSIONS: Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice.

Evaluation of primary care physicians' competence in selective skin tumour triage after short versus long dermoscopy training: a randomized non-inferiority trial.

BACKGROUND: Although primary care physicians (PCPs) play a key role in skin cancer screening, their skills in detecting malignant tumours is suboptimal. OBJECTIVES: To determine whether a short dermoscopy e-learning course (4 h) in skin tumour diagnosis for PCPs is non-inferior to a long course (12 h) in selective triage of skin lesions. Secondly, to evaluate whether regular refresher training sessions are necessary to maintain the PCPs' skills in the medium term. METHODS: A randomized 2 × 2 factorial non-inferiority trial was conducted online over an 8-month period among 233 PCPs including 126 certified general practitioners, 94 PCPs in training, and 13 occupational physicians, all without prior advanced dermoscopy training. Participants were randomized 1:1:1:1 to receive short training and mandatory refreshers (n = 58), short training and optional refreshers (n = 59), long training and mandatory refreshers (n = 58), or long training and optional refreshers (n = 58). PCPs' skills were evaluated before training (T0), immediately after training (T1) to test the non-inferiority, and after 5 months (T2) to evaluate the impact of the refreshers. The primary endpoint was the difference in the change of score after short and long training. The non-inferiority margin was set at -28%. RESULTS: Among the 233 randomized participants, 216 (93%) completed T1 and 197 (84.5%) completed T2. For short versus long training, the primary endpoint was 1.392 (95% CI: 0.138; 2.645) in the per-protocol population (p < 0.001) and 1.016 (95% CI: -0.224; 2.256) in the modified intention-to-treat population (p < 0.001). After training, the type of refresher showed no impact on the score (p = 0.840). However, PCPs who completed all refreshers showed the best mean overall score at T2 (p < 0.001). CONCLUSIONS: These findings confirm that short dermoscopy e-learning is non-inferior in training PCPs to triage skin lesions compared to long training. After training, regular refreshers are important to maintain the PCPs' acquired skills over time.

Medication-related osteonecrosis of the jaw, a risk to reassess in osteoporotic patients.

INTRODUCTION: The use of antiresorptive drugs concerns many medical specialties either in relation to their prescription for osteoporosis or cancer, or in relation to the treatment of their side effects. In the literature, less than 10% of medication-related osteonecrosis of the jaw are related to patients treated for osteoporosis, while 90% are found in patients treated for cancer. Despite the increasing number of osteoporotic patients taking high doses of antiresorptive drugs, only few studies describe this topic. The main aim of this study was to highlight the occurrence of medication-related osteonecrosis of the jaw in osteoporotic patients compared to cancer patients. The second aim was to highlight risk factors in the two groups, to try to understand the high number of osteoporotic patients in our population. MATERIALS AND METHODS: A retrospective study was conducted between December 2004 and March 2021 to identify all cases of medication-related osteonecrosis of the jaw in our department with emphasis on the osteoporotic population. Demographic, systemic and local risk factors were collected as well as the type, dose and duration of the anti-resorptive drugs treatment. Evolution and follow-up were also recorded. RESULTS: One hundred sixty five patients presented with medication-related osteonecrosis of the jaw, of whom 67 (40,6%) were osteoporotic. Seventeen (25,4%) patients were males and 50 females (74,6%). Risk factors were tobacco consumption (28,4%), anemia (20,9%), alcohol consumption (19,4%). Use of corticoids or anticoagulant/antithrombotic therapy was related in 20,9% and 16,4%, respectively. The mean age at MRONJ diagnosis was 74,4 (50-98). The mean follow up time was 23,7 months (1-110). CONCLUSION: Unlike the literature where medication-related osteonecrosis of the jaw in osteoporotic patients represents less than 10%, the rate in our series was much higher and represents 40% of the patients. This highlights the importance of a complete dental examination before and during antiresorptive drugs treatment, even in the case of osteoporotic patients.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer: a 13 years-retrospective monocentric study.

Background and study aim: Over the last 20 years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has progressively become a therapeutic option for peritoneal carcinomatosis thanks to its favourable oncologic results. The aim of this study is to analyse the overall survival and recurrence-free survival, after complete CRS and closed abdomen technique HIPEC for peritoneal carcinomatosis from colorectal cancer. Patients and methods: This retrospective study collected the data from all patients who underwent a CRS with HIPEC for colorectal cancer at "Cliniques universitaires Saint Luc" from October 2007 to December 2020. Ninety-nine patients were included. Results: The median follow-up was 34 months. Post-operative mortality and Clavien-Dindo grade III/IV morbidity rates were 2.0% and 28.3%. The overall 2-year and 5-year survival rates were 80.1% and 54.4%. Using the multivariate analysis, age at surgery, liver metastases and PCI score >13 showed a statistically significant negative impact on overall survival. The 2-year and 5-year recurrence-free survival rates were 33.9% and 22%. Using the multivariate analysis, it was found that liver metastases, the extent of carcinomatosis with PCI>7 have a statistically significant negative impact on recurrence-free survival. Conclusions: Despite a high recurrence rate, CRS followed by HIPEC to treat peritoneal carcinomatosis from colorectal origin offer encouraging oncologic results with a satisfying survival rate. When PCI>13, CRS and HIPEC does not seem to offer any survival benefit and to efficiently limit recurrence, our data are in favor of a maximum PCI of 7.

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

INTRODUCTION: Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people. OBJECTIVE: The aim of this study was to assess the detectability of MEs with a STOPP/START-based in-hospital medication review in older people with polypharmacy and multimorbidity prior to a potentially preventable DRA. METHODS: Hospitalised older patients (n = 963) with polypharmacy and multimorbidity from the intervention arm of the OPERAM trial received a STOPP/START-based in-hospital medication review by a pharmacotherapy team. Readmissions within 1 year after the in-hospital medication review were adjudicated for drug-relatedness. A retrospective assessment was performed to determine whether MEs identified at the first DRA were detectable during the in-hospital medication review. RESULTS: In total, 84 of 963 OPERAM intervention patients (8.7%) were readmitted with a potentially preventable DRA, of which 72 patients (n = 77 MEs) were eligible for analysis. About half (48%, n = 37/77) of the MEs were not present during the in-hospital medication review and therefore were not detectable at that time. The pharmacotherapy team recommended a change in medication regimen in 50% (n = 20/40) of present MEs, which corresponds to 26% (n = 20/77) of the total identified MEs at readmission. However, these recommendations were not implemented. CONCLUSION: MEs identified at readmission were not addressed by a prior single in-hospital medication review because either these MEs occurred after the medication review (~50%), or no recommendation was given during the medication review (~25%), or the recommendation was not implemented (~25%). Future research should focus on optimisation of the timing and frequency of medication review and the implementation of proposed medication recommendations. REGISTRATION: ClinicalTrials.gov identifier: NCT02986425. December 8, 2016. FUNDING: European Union HORIZON 2020, Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss National Science Foundation (SNSF).

Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer.

BACKGROUND: Trastuzumab emtansine (T-DM1) is indicated as second-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. We wished to determine if the line of treatment in which T-DM1 is administered has an impact on progression-free survival (PFS) and in particular, if prior treatment with capecitabine/lapatinib or pertuzumab modifies PFS of further treatment with T-DM1. PATIENTS AND METHODS: We performed a multicenter retrospective study in 3 Belgian institutions. We evaluated PFS with T-DM1 in patients treated for HER2 positive metastatic or locally advanced unresectable breast cancer between January 1, 2009 and December 31, 2016. RESULTS: We included 51 patients. The median PFS was 9.01 months. The line of treatment in which T-DM1 (1st line, 2nd line, 3rd line or 4+ lines) was administered had no influence on PFS (hazard ratio 0.979, CI95: 0.835-1.143). There was no significant difference in PFS whether or not patients had received prior treatment with capecitabine/lapatinib (9.17 vs 5.56 months, p-value 0.875). But, patients who received pertuzumab before T-DM1 tended to exhibit a shorter PFS (3.55 months for T-DM1 after pertuzumab vs 9.50 months for T-DM1 without pretreatment with pertuzumab), even if this difference was not statistically significant (p-value 0.144). CONCLUSION: Unlike with conventional chemotherapy, the line of treatment in which T-DM1 is administered does not influence PFS in our cohort of patients with advanced HER2-positive breast cancer.

Optimizing Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older Adults (OPERAM): cluster randomised controlled trial.

OBJECTIVE: To examine the effect of optimising drug treatment on drug related hospital admissions in older adults with multimorbidity and polypharmacy admitted to hospital. DESIGN: Cluster randomised controlled trial. SETTING: 110 clusters of inpatient wards within university based hospitals in four European countries (Switzerland, Netherlands, Belgium, and Republic of Ireland) defined by attending hospital doctors. PARTICIPANTS: 2008 older adults (≥70 years) with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 drugs used long term). INTERVENTION: Clinical staff clusters were randomised to usual care or a structured pharmacotherapy optimisation intervention performed at the individual level jointly by a doctor and a pharmacist, with the support of a clinical decision software system deploying the screening tool of older person's prescriptions and screening tool to alert to the right treatment (STOPP/START) criteria to identify potentially inappropriate prescribing. MAIN OUTCOME MEASURE: Primary outcome was first drug related hospital admission within 12 months. RESULTS: 2008 older adults (median nine drugs) were randomised and enrolled in 54 intervention clusters (963 participants) and 56 control clusters (1045 participants) receiving usual care. In the intervention arm, 86.1% of participants (n=789) had inappropriate prescribing, with a mean of 2.75 (SD 2.24) STOPP/START recommendations for each participant. 62.2% (n=491) had ≥1 recommendation successfully implemented at two months, predominantly discontinuation of potentially inappropriate drugs. In the intervention group, 211 participants (21.9%) experienced a first drug related hospital admission compared with 234 (22.4%) in the control group. In the intention-to-treat analysis censored for death as competing event (n=375, 18.7%), the hazard ratio for first drug related hospital admission was 0.95 (95% confidence interval 0.77 to 1.17). In the per protocol analysis, the hazard ratio for a drug related hospital admission was 0.91 (0.69 to 1.19). The hazard ratio for first fall was 0.96 (0.79 to 1.15; 237 v 263 first falls) and for death was 0.90 (0.71 to 1.13; 172 v 203 deaths). CONCLUSIONS: Inappropriate prescribing was common in older adults with multimorbidity and polypharmacy admitted to hospital and was reduced through an intervention to optimise pharmacotherapy, but without effect on drug related hospital admissions. Additional efforts are needed to identify pharmacotherapy optimisation interventions that reduce inappropriate prescribing and improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02986425.

Safety of systemic anti-cancer treatment in oncology patients with non-severe COVID-19: a cohort study.

BACKGROUND: The viral pandemic coronavirus disease 2019 (COVID-19) has disrupted cancer patient management around the world. Most reported data relate to incidence, risk factors, and outcome of severe COVID-19. The safety of systemic anti-cancer therapy in oncology patients with non-severe COVID-19 is an important matter in daily practice. METHODS: ONCOSARS-1 was a single-center, academic observational study. Adult patients with solid tumors treated in the oncology day unit with systemic anti-cancer therapy during the initial phase of the COVID-19 pandemic in Belgium were prospectively included. All patients (n = 363) underwent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serological testing after the first peak of the pandemic in Belgium. Additionally, 141 of these patients also had a SARS-CoV-2 RT-PCR test during the pandemic. The main objective was to retrospectively determine the safety of systemic cancer treatment, measured by the rate of adverse events according to the Common Terminology Criteria for Adverse Events, in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative patients. RESULTS: Twenty-two (6%) of the 363 eligible patients were positive for SARS-CoV-2 by RT-PCR and/or serology. Of these, three required transient oxygen supplementation, but none required admission to the intensive care unit. Hematotoxicity was the only adverse event more frequently observed in SARS-CoV-2 -positive patients than in SARS-CoV-2-negative patients: 73% vs 35% (P < 0.001). This association remained significant (odds ratio (OR) 4.1, P = 0.009) even after adjusting for performance status and type of systemic treatment. Hematological adverse events led to more treatment delays for the SARS-CoV-2-positive group: 55% vs 20% (P < 0.001). Median duration of treatment interruption was similar between the two groups: 14 and 11 days, respectively. Febrile neutropenia, infections unrelated to COVID-19, and bleeding events occurred at a low rate in the SARS-CoV-2-positive patients. CONCLUSION: Systemic anti-cancer therapy appeared safe in ambulatory oncology patients treated during the COVID-19 pandemic. There were, however, more treatment delays in the SARS-CoV-2-positive population, mainly due to a higher rate of hematological adverse events.

Dental prevention of maxillo-mandibular osteoradionecrosis: A ten-year retrospective study.

INTRODUCTION: Osteoradionecrosis (ORN) remains a frequent complication of radiotherapy in head and neck cancer. As ORN management is often complex, it is essential to focus on its prevention, mainly by dental prophylaxis. The objectives of this study were to evaluate a dental preventive approach based on ORN data and to highlight individual risk factors statistically associated with time-to-ORN. MATERIALS AND METHODS: A retrospective study (January 2004-December 2013) included 415 patients with head and neck cancer who received radiotherapy in their treatment with at least 50 Grays on maxillo-mandibular bones. Pre-radiotherapy dental assessment (clinical and radiological) and prevention (with standardised extraction protocol) were performed. RESULTS: The ORN rate was 7.5%, with a dental origin in 35.5% of cases, mainly represented by dental infection in exclusive mandibular locations. More than 90% of patients were partially or completely dentate, and more than 70% had poor oral hygiene. Dental extractions were performed in 67.9% of patients before radiotherapy and in 42.9% after radiotherapy. Statistically significant risk factors associated with time-to-ORN were addictions (tobacco and alcohol), diabetes, oropharyngeal tumour location, combination of surgery followed by radiotherapy and post-radiotherapy dental extractions. DISCUSSION AND CONCLUSION: Considering that ORN implies severe disabilities and complex management, the rate of 7.5% is unacceptable. A better dental prevention could reduce this rate by one-third. Dental extractions could be systematic in high-dose irradiation mandibular areas in patients presenting with poor oral hygiene and/or statistically significant risk factors for the occurrence of ORN. Moreover, favourable oral condition after radiotherapy should be maintained.

Prescribing medicines to older people-How to consider the impact of ageing on human organ and body functions.

Ageing is associated with several changes in human organs, which result in altered medication pharmacokinetics and pharmacodynamics. Ageing is also associated with changes in human body functions, such as impaired vision, hearing, swallowing, motor and cognitive functions, which can affect the adequate intake and administration of drugs. As a consequence, older people, and especially patients older than 75 years, are the main users of many drugs and they frequently use 5 drugs or more long-term (i.e. polypharmacy). All this increases the complexity of adequate drug intake, administration and adherence. However, there is a lack of evidence on the considerations that should be taken into account to ensure appropriate drug prescribing to older people. This review article summarizes the most clinically relevant changes in human organ and body functions and the consequential changes in pharmacokinetics and pharmacodynamics in older people, along with possible dosing consequences or alternatives for drugs frequently prescribed to this patient population. Recommendations are given on how ageing could be considered in clinical drug development, drug authorization and appropriate prescribing.

Single-incision laparoscopic surgery for locally advanced colorectal cancer : feasibility, short-term and oncologic outcomes.

BACKGROUND AND STUDY AIMS: Data about single-incision laparoscopic surgery (SILS) in locally advanced colorectal cancers are scarce. This study aimed to evaluate perioperative and shortterm oncologic outcomes of SILS in pT3-T4 colorectal cancer. PATIENTS AND METHODS: From 2011 to 2015 data from 249 SILS performed in our Colorectal Unit were entered into a prospective database. Data regarding patients with a pT3-T4 colorectal adenocarcinoma were compared to those with pTis-pT2. Factors influencing conversion were assessed by multivariate analysis. RESULTS: There were 100 consecutive patients (T3-T4 = 70, Tis-T2 = 30). Demographics were similar. Tumor size was significantly larger in the T3-T4 group [3.9cm vs 2cm; p<0.001]. In T3-T4 patients we found a significant higher number of lymph nodes harvested [20 vs 13 ; p<0.001]. Early (<30 days) severe (Clavien-Dindo classification>2) postoperative complication rate was similar between groups (8.6% vs 10% ; p = 0.999), as well as conversion rate (18.6% vs 6.7% ; p = 0.220). Finally, there were no differences in terms of hospital stay and mortality rate. On multivariate analysis, age (OR = 1.06, 95%CI: 1.012-1.113 ; p = 0.015] and stage IV (OR = 5.372, 95%CI: 1.320-21.862, p = 0.019) were independently associated with conversion. CONCLUSIONS: SILS for locally advanced colorectal cancer did not affect the short-term outcomes in this series and oncological clearance remained satisfactory. Age and stage IV disease are independent risk factors for conversion.

The Systematic Tool to Reduce Inappropriate Prescribing (STRIP): Combining implicit and explicit prescribing tools to improve appropriate prescribing.

Inappropriate prescribing is a major health care issue, especially regarding older patients on polypharmacy. Multiple implicit and explicit prescribing tools have been developed to improve prescribing, but these have hardly ever been used in combination. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) combines implicit prescribing tools with the explicit Screening Tool to Alert physicians to the Right Treatment and Screening Tool of Older People's potentially inappropriate Prescriptions criteria and has shared decision-making with the patient as a critical step. This article describes the STRIP and its ability to identify potentially inappropriate prescribing. The STRIP improved general practitioners' and final-year medical students' medication review skills. The Web-application STRIP Assistant was developed to enable health care providers to use the STRIP in daily practice and will be incorporated in clinical decision support systems. It is currently being used in the European Optimizing thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly (OPERAM) project, a multicentre randomized controlled trial involving patients aged 75 years and older using multiple medications for multiple medical conditions. In conclusion, the STRIP helps health care providers to systematically identify potentially inappropriate prescriptions and medication-related problems and to change the patient's medication regimen in accordance with the patient's needs and wishes. This article describes the STRIP and the available evidence so far. The OPERAM study is investigating the effect of STRIP use on clinical and economic outcomes.

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology.

Lymph node ratio and surgical quality are strong prognostic factors of rectal cancer: results from a single referral centre.

AIM: Nodal stage is a strong prognostic factor of oncological outcome of rectal cancer. To compensate for the variation in total number of harvested nodes, calculation of the lymph node ratio (LNR) has been advocated. The aim of the study was to compare the impact, on the long-term oncological outcome, of the LNR with other predictive factors, including the quality of total mesorectal excision (TME) and the state of the circumferential resection margin. METHOD: Consecutive patients having elective surgery for nonmetastatic rectal cancer were extracted from a prospectively maintained database. Retrospective uni- and multivariate analyses were performed based on patient-, surgical- and tumour-related factors. The prognostic value of the LNR on overall survival (OS) and on overall recurrence-free survival (ORFS) was assessed and a cut-off value was determined. RESULTS: From 1998 to 2013, out of 456 patients, 357 with nonmetastatic disease were operated on for rectal cancer. Neoadjuvant radiochemotherapy was administered to 66.7% of the patients. The mean number of lymph nodes retrieved was 12.8 ± 8.78 per surgical specimen. A lower lymph node yield was obtained in patients who received neoadjuvant chemoradiotherapy (11.8 vs 14.2; P = 0.014). The 5-year ORFS was 71.8% and the 5-year OS was 80.1%. Multivariate analysis confirmed LNR, the quality of TME and age to be independent prognostic factors of OS. LNR, age and perineural infiltration were independently associated with ORFS. Low- and high-risk patients could be discriminated using an LNR cut-off value of 0.2. CONCLUSION: LNR is an independent prognostic factor of OS and ORFS. In line with the principles of optimal surgical management, the quality of TME and lymph node yield are essential technical requirements.

Adherence with Dosing Guideline in Patients with Impaired Renal Function at Hospital Discharge.

OBJECTIVES: To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge. DESIGN: Retrospective cohort study between January 2007 and July 2011. SETTING: Academic teaching hospital in the Netherlands. SUBJECTS: Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73 m(2) at discharge and prescribed one or more medicines of which the dose is renal function dependent. MAIN OUTCOME MEASURES: The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR<30 and moderate: eGFR 30-50 ml/min/1.73 m(2)). Furthermore, the potential clinical relevance of non-adherence was assessed. RESULTS: 1327 patients were included, mean age 67 years, mean eGFR 38 ml/min/1.73 m(2). Adherence with the guideline was present in 53.9% (n=715) of patients. Reporting the eGFR, which was incorporated since April 2009, resulted in more adherence with the guideline: 50.7% vs. 57.0%, RR 1.12 (95% CI 1.02-1.25). Adherence was less in patients with severe renal impairment (46.0%), compared to patients with moderate renal impairment (58.1%, RR 0.79; 95% CI 0.70-0.89). 71.4% of the cases of non-adherence had the potential to cause moderate to severe harm. CONCLUSION: Required dosage adjustments in case of impaired renal function are often not performed at hospital discharge, which may cause harm to the majority of patients. Reporting the eGFR can be a small and simple first step to improve adherence with dosing guidelines.

Computerized Decision Support Improves Medication Review Effectiveness: An Experiment Evaluating the STRIP Assistant's Usability.

BACKGROUND: Polypharmacy poses threats to patients' health. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) is a drug optimization process for conducting medication reviews in primary care. To effectively and efficiently incorporate this method into daily practice, the STRIP Assistant--a decision support system that aims to assist physicians with the pharmacotherapeutic analysis of patients' medical records--has been developed. It generates context-specific advice based on clinical guidelines. OBJECTIVE: The aim of this study was to validate the STRIP Assistant's usability as a tool for physicians to optimize medical records for polypharmacy patients. METHODS: In an online experiment, 42 physicians were asked to optimize medical records for two comparable polypharmacy patients, one in their usual manner and one using the STRIP Assistant. Changes in effectiveness were measured by comparing respondents' optimized medicine prescriptions with medication prepared by an expert panel of two geriatrician-pharmacologists. Efficiency was operationalized by recording the time the respondents took to optimize the two cases. User satisfaction was measured with the System Usability Scale (SUS). Independent and paired t tests were used for analysis. RESULTS: Medication optimization significantly improved with the STRIP Assistant. Appropriate decisions increased from 58% without the STRIP Assistant to 76% with it (p < 0.0001). Inappropriate decisions decreased from 42% without the STRIP Assistant to 24% with it (p < 0.0001). Participants spent significantly more time optimizing medication with the STRIP Assistant (24 min) than without it (13 min; p < 0.0001). They assigned it a below-average SUS score of 63.25. CONCLUSION: The STRIP Assistant improves the effectiveness of medication reviews for polypharmacy patients.

Glioblastoma surgery with and without intraoperative MRI at 3.0T.

BACKGROUND: Gross total or near total resection (GTR/NTR; resection ≥95%) of glioblastoma (GBM) seems correlated with a longer survival. Intraoperative MRI (ioMRI) is one method to evaluate the extent of resection (EOR) in order to improve it during the same anesthesia. We compared GBM resections using a 3.0T ioMRI and then without considering the EOR, safety, survival and discussed the indications for using this expensive modality. METHODS: Between March 2006 and November 2011, 56 GBM resections were performed using an ioMRI, and 38 without (control group). The only criterion in order to have access to the ioMRI was its availability. We compared the variables EOR, Karnofsky Performance Scale scores and survival in both groups. RESULTS: In the ioMRI group, 15 patients (26.8%) underwent an immediate second resection increasing the GTR rate of 10.7% and the GTR/NTR rate of 8.9%. There was a significant difference between the use of an ioMRI and the control group in reaching a larger EOR (P=0.049, Fisher's exact test). The effect of using the ioMRI or not on the overall survival, with EOR as covariate, was not significant (P=0.147, Likelihood ratio test). However, the EOR alone had a significant effect on survival (P=0.049, Wald test), with a shorter survival for the patients with a partial resection (PR) than a GTR/NTR (Hazard ratio=1.6, 95% CI HR: 1.00-2.69), with a median overall survival of 15.26 months (95% CI: 12.34-19.08) for the GTR/NTR subgroup versus 10.26 months (95% CI: 6.64-15.82) for the PR subgroup. Multivariate regression analysis also identified age, sex and adjuvant chemotherapy as factors significantly associated with overall survival. CONCLUSIONS: A 3.0T ioMRI improved the quality of resection by 17.8% and increased the GTR/NTR rate by 8.9% up to 73.2% without additional morbidity. A GTR/NTR improves survival duration by about 50%. Thus, it remains reasonable to increase the EOR to reach GTR/NTR using an intraoperative control. However, ioMRI should be limited to the cases for which a GTR/NTR seems preoperatively possible.

Use of a structured medication history to establish medication use at admission to an old age psychiatric clinic: a prospective observational study.

OBJECTIVE: Medication reconciliation results in fewer adverse drug events. The first step in medication reconciliation is to carry out a structured interview about medication use. It is not known whether such an interview is useful in inpatient old age psychiatry. The object of this study was to determine at admission the number of discrepancies in medication use, comparing the structured history of medication use (SHIM) procedure with the usual procedure for taking the medication history. METHODS: A prospective observational study was conducted. All consecutive patients aged 55 years and older admitted from January until April 2011 to the inpatient old age psychiatric clinic of a large psychiatric teaching hospital in The Hague, the Netherlands, were eligible for inclusion; 50 patients were included. In every patient, the usual procedure (medication history-taking at admission by the treating physician) was compared with the SHIM procedure administered by the researcher. The SHIM procedure consists of a structured interview with the patient about the actual use of medication, incorporating the information from the community pharmacy and the patient's medications brought to the interview. The main outcome was the number of discrepancies in recorded medication use between the SHIM and the usual procedure. RESULTS: In total, 100 discrepancies (median 2 per patient, range 0-8) in medication use were identified; 78 % (n = 39) of the patients had at least one discrepancy. Of the discrepancies, 69 % were drug omissions, and 31 % were drug additions or discrepancies in the frequency or dosage of medications. Eighty-two percent of all discrepancies were potentially clinically relevant. In 24 % of the patients, the discrepancies had clinical consequences. CONCLUSION: The number of discrepancies that were found suggests that the usual procedure for taking the medication history can be improved. The SHIM procedure enables a comprehensive and accurate overview of the medication used by older patients admitted to a psychiatric hospital, and contributes to the prevention of clinically relevant adverse drug events.