Long-term safety of withholding standard prophylaxis in patients with moderate chronic kidney disease.

In the latest ESUR contrast media guidelines, standard prophylaxis is no longer recommended for patients with moderate chronic kidney disease (CKD). In the absence of solid evidence, guideline updates are often based on indirect evidence and expert opinion. Likewise, evidence supporting the withdrawal of standard prophylaxis in moderate CKD patients was scarce and mostly indirect, but did include one randomised controlled trial evaluating guideline-recommended standard prophylactic intravenous hydration against a group receiving no prophylaxis (A MAastricht Contrast-Induced Nephropathy Guideline (AMACING) trial). Since then, benefits of the updated guideline recommendation for patient and hospital burden have been numerated and were shown to be substantial. The current special report provides data on long-term safety from the AMACING randomised controlled trial. KEY POINTS: • In the latest version of ESUR clinical practice guidelines for safe use of contrast media, standard prophylaxis is no longer recommended for patients with moderate chronic kidney disease. • Benefits of this change in recommendations for patient and hospital burden have been numerated. The current report provides data on long-term safety from the AMACING randomised controlled trial. • No disadvantage of withholding prophylaxis could be discerned. Results suggest that, in this population, underlying disease is more relevant for survival and prognosis than contrast administration itself.

Prevalence of nodal involvement in rectal cancer after chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data. METHODS: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219) months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P < 0.001). Cox regression analyses showed ypN+ status to be an independent predictor of recurrence and death. CONCLUSION: Risk of nodal metastases (ypN+) after chemoradiotherapy increases with advancing ypT category and needs to be considered if an organ-preserving strategy is contemplated.

When patients are diagnosed with rectal cancer and the tumour grows beyond the rectal wall there is a high risk that the tumour has spread to nearby lymph nodes. This study showed that this relationship between tumour invasion depth and lymph node involvement is similar after treatment with (chemo)radiotherapy. Patients who have tumour cells remaining in the lymph nodes after (chemo) radiotherapy have a worse prognosis than patients who do not have cancer cells remaining in the lymph nodes. When an organ-preserving treatment is considered as an alternative therapy, this should be kept in mind during patient counselling.

A trial-based cost-effectiveness analysis of topical 5-fluorouracil vs. imiquimod vs. ingenol mebutate vs. methyl aminolaevulinate conventional photodynamic therapy for the treatment of actinic keratosis in the head and neck area performed in the Netherlands.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin condition that might have the ability to progress into squamous cell carcinoma. Due to the high incidence of AK, treatment of this disease significantly impacts healthcare spending. OBJECTIVES: To determine which commonly prescribed field-directed treatment is the most cost-effective, when comparing 5-fluorouracil (5-FU) 5%, imiquimod (IMQ) 5%, ingenol mebutate (IM) 0·015% and methyl aminolaevulinate photodynamic therapy (MAL-PDT) for AK in the head and neck region. METHODS: We performed an economic evaluation from a healthcare perspective. Data were collected alongside a single-blinded, prospective, multicentre randomized controlled trial with 624 participants in the Netherlands. The outcome measure was expressed as the incremental cost-effectiveness ratio, which is the incremental costs per additional patient with ≥ 75% lesion reduction compared with baseline. This trial was registered at ClinicalTrials.gov, number NCT02281682. RESULTS: The trial showed that 5-FU was the most effective field treatment for AK in the head and neck region. Twelve months post-treatment, the total mean costs for 5-FU were significantly lower (€433) than the €728, €775 and €1621 for IMQ, IM and MAL-PDT, respectively. The results showed that 5-FU was a dominant cost-effective treatment (more effective and less expensive) compared with the other treatments, 12 months post-treatment. CONCLUSIONS: Based on these results, we consider 5-FU 5% cream as the first-choice treatment option for multiple AKs in the head and neck area. What's already known about this topic? Due to the increasing incidence of actinic keratosis (AK), the recommended treatment results in a considerable socioeconomic burden for (dermatological) healthcare. Although cost-effectiveness modelling studies have been performed in which different treatments for AK were compared, a prospective clinical trial comparing four frequently prescribed treatments on effectiveness and resource consumption within a time horizon of 12 months has never been conducted. What does this study add? This is the first study examining the cost-effectiveness of 5-fluorouracil 5% cream, imiquimod 5% cream, ingenol mebutate 0·015% gel and methyl aminolaevulinate photodynamic therapy, with data collected in a randomized controlled trial over a time horizon of 12 months. We found that 5-fluorouracil was a dominant cost-effective treatment (more effective and less costly), based on data from the Netherlands. Linked Comment: Steeb et al. Br J Dermatol 2020; 183:612.

Impact on clinical practice of updated guidelines on iodinated contrast material: CINART.

OBJECTIVE: Guidelines on safe use of iodinated contrast material recommend intravenous prophylactic hydration to prevent post-contrast adverse (renal) effects. Recently, guidelines have been updated and standard prophylaxis is no longer recommended for the majority of patients. The current study aims to evaluate the consequences for clinical practice of the updated guidelines in terms of complications, hospitalisations, and costs. METHODS: The Contrast-Induced Nephropathy After Reduction of the prophylaxis Threshold (CINART) project is a retrospective observational study. All elective procedures with intravascular iodinated contrast administration at Maastricht University Medical Centre (UMC+) in patients aged > 18 years, formerly eligible for prophylaxis (eGFR 30-44 ml/min/1.73 m2 or eGFR 45-59 ml/min/1.73 m2 in combination with diabetes or > 1 predefined risk factor), and currently eligible for prophylaxis (eGFR < 30 ml/min/1.73 m2) were included. Data were used to calculate relative reductions in complications, hospitalisations, and costs associated with standard prophylactic intravenous hydration. CINART is registered with Clinicaltrials.gov: NCT03227835. RESULTS: Between July 1, 2017, and July 1, 2018, 1992 elective procedures with intravascular iodinated contrast in patients formerly and currently eligible for prophylaxis were identified: 1808 in patients formerly eligible for prophylaxis and 184 in patients currently eligible for prophylaxis. At Maastricht UMC+, guideline updates led to large relative reductions in numbers of complications of prophylaxis (e.g. symptomatic heart failure; - 89%), extra hospitalisations (- 93%), and costs (- 91%). CONCLUSION: Guideline updates have had a demonstrable impact on daily clinical practice benefiting patient, hospital, and health care budgets. Clinical practice varies between institutions and countries; therefore, a local estimation model is provided with which local impact on costs, hospitalisations, and complications can be calculated. KEY POINTS: • Clinical practice guidelines recommend prophylactic intravenous hydration to prevent post-contrast adverse outcomes such as contrast-induced acute kidney injury. • Clinical practice guidelines have recently been updated, and standard prophylaxis is no longer recommended for the majority of patients. • The guideline updates have a large impact on daily clinical practice: relative reductions at Maastricht UMC+ were - 89% prophylaxis complications, - 93% hospitalisations, and - 91% costs, and similar reductions are expected for Dutch and adherent European medical centres.

The diagnostic accuracy of 1.5 T versus 3 T non-echo-planar diffusion-weighted imaging in the detection of residual or recurrent cholesteatoma in the middle ear and mastoid.

PURPOSE AND BACKGROUND: This study retrospectively compares diagnostic performance of 1.5 T versus 3 T non-echo planar diffusion weighted imaging with or without additional T1 and T2 sequences in the detection of residual and/or recurrent cholesteatoma. METHODS: Patients with clinically suspected recurrent cholesteatoma or postoperative routine survey MR who subsequently underwent surgical procedure were retrospectively included (135 patients, 164 operated ears) from a large database. Patients underwent 1.5 T (128 ears) or 3 T MRI (36 ears), with non-echo planar DWI, T1 and T2 acquisitions. Two radiologists independently reassessed the images. Definitive surgical diagnosis was used as gold standard. Sensitivity, specificity and diagnostic odds ratio were evaluated. RESULTS: According to surgical diagnosis a cholesteatoma was present in 124 of 164 ears, corresponding with a prevalence of 75%. Sensitivity and specificity were lower for 3 T compared to 1.5 T, irrespective of whether additional T1 and T2-weighted sequences were used or not. Diagnostic odds ratios were higher for 1.5 T (34 and 12 for reader 1 and 2, respectively) compared to 3 T (3 and 4 for reader 1 and 2, respectively). Adding T1 and T2 sequences lowers sensitivity but increases specificity. CONCLUSION: Non-epi DWI for the detection of residual/recurrent cholesteatoma is preferably performed on 1.5 T scanners over 3 T. The use of additional sequences regarding detection of cholesteatoma is debatable as it lowers sensitivity but increases specificity. However, these sequences may also be of use in diagnosing complications and planning surgical procedures in some hospitals.

Evaluation of single-view contrast-enhanced mammography as novel reading strategy: a non-inferiority feasibility study.

BACKGROUND: Guidelines recommend screening of high-risk women using breast magnetic resonance imaging (MRI). Contrast-enhanced mammography (CEM) has matured, providing excellent diagnostic accuracy. To lower total radiation dose, evaluation of single-view (1 V) CEM exams might be considered instead of double-view (2 V) readings as an alternative reading strategy in women who cannot undergo MRI. METHODS: This retrospective non-inferiority feasibility study evaluates whether the use of 1 V results in an acceptable sensitivity for detecting breast cancer (non-inferiority margin, - 10%). CEM images from May 2013 to December 2017 were included. 1 V readings were performed by consensus opinion of three radiologists, followed by 2 V readings being performed after 6 weeks. Cases were considered "malignant" if the final BI-RADS score was ≥ 4, enabling calculation of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Histopathological results or follow-up served as a gold standard. RESULTS: A total of 368 cases were evaluated. Mean follow-up for benign or negative cases was 20.9 months. Sensitivity decreased by 9.6% from 92.9 to 83.3% when only 1 V was used for evaluation (p < 0.001). The lower limit of the 90% confidence interval around the difference in sensitivity between 1 V and 2 V readings was - 15% and lies below the predefined non-inferiority margin of - 10%. Hence, non-inferiority of 1 V to 2 V reading cannot be concluded. AUC for 1 V was significantly lower, 0.861 versus 0.899 for 2 V (p = 0.0174). CONCLUSION: Non-inferiority of 1 V evaluations as an alternative reading strategy to standard 2 V evaluations could not be concluded. 1 V evaluations had lower diagnostic performance compared with 2 V evaluations. KEY POINTS: • To lower radiation exposure used in contrast-enhanced mammography, we studied a hypothetical alternative strategy: single-view readings (1 V) versus (standard) double-view readings (2 V). • Based on our predefined margin of - 10%, non-inferiority of 1 V could not be concluded. • 1 V evaluation is not recommended as an alternative reading strategy to lower CEM-related radiation exposure.

Characteristics of a novel citizen rescue system for out-of-hospital cardiac arrest in the Dutch province of Limburg: relation to incidence and survival.

BACKGROUND: We evaluated the characteristics of a novel text message system notifying citizen rescuers in cases of out-of-hospital circulatory arrest (OHCA) in the Dutch province of Limburg, including their relation to incidence and survival. METHODS AND RESULTS: The study area comprised 2,153 km2 (831 mi2) with 1.12 mio. inhabitants. During the 2­year study period approximately 9,000 volunteers were registered, about 60% male, 59% with no experience in actual resuscitation, and 27.4% healthcare professionals. The system was not activated in 557 of 1,085 (51.3%) OHCAs, frequently because there was no resuscitation setting present yet at the time of the emergency call. Rescuers were notified on 1,076 occasions, with no resuscitation setting being present in 548 of 1,076 (50.9%) notifications. OHCA incidence rates were 67 per 100,000 inhabitants per year, 95 per 100,000 men and 39 per 100,000 women standardised for age with the European Standard Population. The mean number of notifications per volunteer was 1.3 times per year. Higher volunteer density was related to increased survival if at least one volunteer attended the cardiac arrest. If the density exceeded 0.75%, survival increased to 34.8% compared to 20.6% at a density below 0.25%. CONCLUSION: In about half of OHCAs needing resuscitation the system was activated and in approximately half of the notifications resuscitation proved to be justified. Volunteers are notified 1.3 times per year on average. Survival was related to volunteer density, suggesting that further improvement can be achieved by increasing the number of citizen rescuers.

Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer and incidence rates are increasing. Photodynamic therapy (PDT) is a frequently used treatment, especially for superficial BCC (sBCC). Two topical photosensitizing agents are currently used to treat sBCC, namely 5-aminolaevulinic acid (ALA) and its ester, methyl aminolaevulinate (MAL). Previous research showed a high efficacy for ALA-PDT using a twofold fractionated illumination scheme in which two light fractions of 20 J cm-2 and 80 J cm-2 were delivered 4 h and 6 h after ALA application. OBJECTIVES: To evaluate whether twofold ALA-PDT is superior to conventional MAL-PDT for sBCC. METHODS: We performed a single-blind, randomized, multicentre trial in the Netherlands. RESULTS: Overall, 162 patients were randomized either to conventional MAL-PDT or twofold ALA-PDT. After 12 months, a total of six treatment failures occurred following ALA-PDT and 13 treatment failures occurred following MAL-PDT. The 12-month cumulative probability of remaining free from treatment failure was 92·3% [95% confidence interval (CI) (83·7-96·5)] for ALA-PDT and 83·4% (95% CI 73·1-90·0) for MAL-PDT (P = 0·091). CONCLUSIONS: The twofold ALA-PDT scheme resulted in fewer recurrences, although the difference between both treatment groups was not statistically significant. However, ALA-PDT resulted in higher pain scores and more post-treatment side-effects compared with MAL-PDT.

The diagnostic accuracy of bleeding assessment tools for the identification of patients with mild bleeding disorders: A systematic review.

INTRODUCTION: The bleeding assessment tool (BAT) has been developed to standardize and interpret bleeding history for mild bleeding disorders. However, a critical appraisal addressing the quality and results of validation studies is lacking. AIM: We performed a systematic review of diagnostic studies assessing the performance of the BAT in patients referred for evaluation of bleeding symptoms. METHODS: The electronic database PubMed was searched from inception through July 27, 2017. Eligible publications were original studies that assessed and validated the diagnostic accuracy of bleeding questionnaires for identification of adults with mild bleeding disorders. For each study, sensitivity, specificity and diagnostic odds ratio (DOR) were calculated. Quality was assessed using the Quality Assessment of Diagnostic studies-2 tool. To assess the influence of specific study characteristics on DOR, univariate meta-regression analyses were performed. RESULTS: Nine studies were included. Five studies investigating the ISTH-BAT or other bleeding questionnaires had a moderate to low DOR. Four studies investigating Vicenza-based BATs had a high DOR, with high specificity (>90%) and sensitivity of 59%-85%. Study characteristics such as case-control design, retrospective data collection and differences in reference standard were associated with optimistic estimates of diagnostic performance. Three of four studies with a high DOR had these study characteristics. Studies with good methodological quality mainly had a low DOR. CONCLUSION: The main advantage of the BAT is that it offers a complete and structured interview. However, the BAT is of limited diagnostic value to the workup of patients referred for bleeding evaluation in clinical practice.

Correction to: Circumstances and causes of sudden circulatory arrests in the Dutch province of Limburg and the involvement of citizen rescuers.

Correction to:Neth Heart J 2017 https://doi.org/10.1007/s12471-017-1057-1 In the version of the article originally published online, there was an error in the last section of the Discussion. It is stated that 'In 42% of the OHCAs a volunteer alert would have been appropriate, but the alert system ….

Circumstances and causes of sudden circulatory arrests in the Dutch province of Limburg and the involvement of citizen rescuers.

BACKGROUND: Recently we showed that a citizen volunteer system using text message alerts improves survival of out-of-hospital sudden circulatory arrest (OHCA). It is important to characterise the OHCA population encountered by the volunteers regarding circumstances and causes of the arrests. METHODS AND RESULTS: Eligible for this study were 968 OHCAs that occurred between April 2012 and April 2014 in the Dutch province of Limburg. The distribution of causes of OHCA, patient characteristics and resuscitation settings were compared between 492 arrests wherein volunteers were notified and 476 arrests where the dispatcher decided not to do so. In case of notification, the cause of OHCA was known in 345 cases and of cardiac origin (treatable) in 83.2% (287/345). About 41% of the cardiac arrests were caused by acute or chronic coronary artery disease. OHCA occurred within the home environment in about 84%. The OHCA was witnessed in 75% of the cases. In 60.9% of the cases a witness or bystander had already started basic life support. However, in approximately 18% of the OHCAs the volunteer was the first to start basic life support before arrival of the ambulance. In about 75% of the OHCAs the ambulance arrived at 6 minutes or later after time of notification by the dispatch centre. CONCLUSION: The volunteer system is predominantly activated in situations for which it was developed; cases with cardiac aetiology (58%) and cases in the home environment (84%). The majority of patients encountered by the volunteers had 'hearts too good to die', underscoring the benefit of deploying citizen rescuers in programs to improve survival of OHCA.

Reliability of the Patient and Observer Scar Assessment Scale and a 4-point scale in evaluating linear facial surgical scars.

BACKGROUND: In order to evaluate and improve aesthetic outcome for patients undergoing dermatological surgery, a reliable evaluation tool must be used. The 4-point scale and the Patient and Observer Scar Assessment Scale (POSAS) were both developed for this purpose. OBJECTIVE: To compare the reliability of the POSAS scale with the 4-point scale for facial linear surgical scars and to assess the influence of different scar characteristics on the overall impression. METHODS: Patients visiting the outpatient clinics of the Maastricht University Medical Centre with linear facial scars were included. The 4-point scale and the Observer Scar Assessment Scale (OSAS) were completed by three independent observers. The Patient Scar Assessment Scale (PSAS) was completed by the patient on the day of the visit and 2 weeks later. The intra-class correlation coefficient (ICC) with corresponding 95% confidence intervals (CI) were calculated to assess the reliability of the scales. Linear multivariate regression analyses were performed to evaluate how the score on each aspect affected the overall opinion. RESULTS: Fifty scars in 50 patients were included. The ICC of the 4-point scale was 0.819 (95% CI: 0.708-0.892) for multiple observers and 0.602 (95% CI: 0.447-0.734) for single observer. These were superior to the ICCs of total OSAS scores (0.783 95% CI: 0.547-0.888 for multiple observers and 0.546 95% CI: 0.287-0.726 for single observer). ICCs of individual sub-items on the OSAS scored even lower. The sub-items contributed differently to the overall opinion among the different observers or patient. CONCLUSION: In terms of reliability, the overall opinion and the 4-point scale were superior to the total POSAS score or the sub-items. Observers do not weight individual scar characteristics equally to arrive at an overall opinion, which challenges the assumption that calculating a total POSAS score by summing of the scores on the individual items is a valid approach.

Photodynamic therapy vs. topical imiquimod for treatment of superficial basal cell carcinoma: a subgroup analysis within a noninferiority randomized controlled trial.

BACKGROUND: A recent noninferiority randomized controlled trial (RCT) indicated that imiquimod can be considered as superior to methylaminolevulinate photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell carcinoma (sBCC). Knowledge of treatment effectiveness in subgroups of patients is of great value in clinical practice to select the most effective treatment for an individual patient with sBCC. OBJECTIVES: To explore whether the relative treatment effect of MAL-PDT and imiquimod is consistent across subgroups defined by patient and tumour characteristics. METHODS: Data were derived from a single-blinded, noninferiority, multicentre RCT comparing MAL-PDT, topical imiquimod and fluorouracil (ISRCTN79701845). Treatment success was defined as free of tumour recurrence at 12-month follow-up. Subgroup analyses were performed for subgroups defined by sex, age, tumour location and tumour size. RESULTS: Two hundred and two patients received MAL-PDT and 198 received imiquimod. The superiority of imiquimod vs. MAL-PDT was observed in subgroups of females, sBCC on the trunk and large tumours with risk differences in favour of imiquimod of 18·4% [95% confidence interval (CI) 7·8-29·0%], 21·0% (95% CI 10·9-31·1%) and 18·9% (95% CI 7·1-30·7%), respectively. Higher probability of treatment success for imiquimod vs. MAL-PDT was consistently found in all other subgroups with the exception of sBCC localized on the lower extremities in older patients. In the latter subgroup, the risk difference at the expense of imiquimod was -57·3% (95% CI -81·7% to -32·9%). CONCLUSIONS: Imiquimod remains the first-choice treatment for sBCC in terms of effectiveness. In older patients with sBCC on the lower extremities MAL-PDT might be preferred. Results should be interpreted carefully as subgroup analyses were exploratory and not driven by prior hypotheses.

Evaluation of low-energy contrast-enhanced spectral mammography images by comparing them to full-field digital mammography using EUREF image quality criteria.

OBJECTIVE: Contrast-enhanced spectral mammography (CESM) examination results in a low-energy (LE) and contrast-enhanced image. The LE appears similar to a full-field digital mammogram (FFDM). Our aim was to evaluate LE CESM image quality by comparing it to FFDM using criteria defined by the European Reference Organization for Quality Assured Breast Screening and Diagnostic Services (EUREF). METHODS: A total of 147 cases with both FFDM and LE images were independently scored by two experienced radiologists using these (20) EUREF criteria. Contrast detail measurements were performed using a dedicated phantom. Differences in image quality scores, average glandular dose, and contrast detail measurements between LE and FFDM were tested for statistical significance. RESULTS: No significant differences in image quality scores were observed between LE and FFDM images for 17 out of 20 criteria. LE scored significantly lower on one criterion regarding the sharpness of the pectoral muscle (p < 0.001), and significantly better on two criteria on the visualization of micro-calcifications (p = 0.02 and p = 0.034). Dose and contrast detail measurements did not reveal any physical explanation for these observed differences. CONCLUSIONS: Low-energy CESM images are non-inferior to FFDM images. From this perspective FFDM can be omitted in patients with an indication for CESM. KEY POINTS: • Low-energy CESM images are non-inferior to FFDM images. • Micro-calcifications are significantly more visible on LE CESM than on FFDM. • There is no physical explanation for this improved visibility of micro-calcifications. • There is no need for an extra FFDM when CESM is indicated.