Validity of the Rotterdam Elderly Pain Observation Scale for institutionalised cognitively impaired Dutch adults.

BACKGROUND: The Rotterdam Elderly Pain Observation Scale (REPOS) has not yet been validated for institutionalised cognitively impaired adults. To fill this gap of knowledge, we tested psychometric properties of the REPOS when used for pain assessment in this population. METHODS: In this multicentre observational study, residents were filmed during a possibly painful moment and at rest. Healthcare professionals were asked to rate residents' pain by means of a Numeric Rating Scale (NRS)-proxy. Two researchers assessed pain with the REPOS and the Chronic Pain Scale for Non Verbal Adults with Intellectual Disabilities (CPS-NAID) from video-recordings. RESULTS: In total, 168 observations from 84 residents were assessed. Inter-observer reliability between the two researchers was good, with Cohen's kappa 0.72 [95% confidence interval (CI) 0.64 to 0.79]. Correlation between the REPOS and CPS-NAID for a possibly painful moment was 0.73 (95% CI 0.65 to 0.79). Sensitivity (85%) and specificity (61%) for the detection of pain were calculated with REPOS ≥ 3 and NRS ≥ 4 as a reference value. Item response theory analysis shows that the item grimace displayed perfect discrimination between residents with and without pain. CONCLUSION: The REPOS is a reliable and valid instrument to assess pain in cognitively impaired individuals.

Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

PURPOSE: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. METHODS: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF < 50% that declined > 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40-50%) and severe cardiotoxicity (LVEF < 40%). Multivariable Cox and mixed model analyses were performed to identify risk factors associated with cardiotoxicity. Additionally, we explored the reversibility of cardiotoxicity in patients who continued trastuzumab. RESULTS: In total, 429 patients were included. Median follow-up for cardiotoxicity was 15 months (interquartile range 8-31 months). The yearly incidence of non-severe + severe cardiotoxicity in the first and second year was 11.7% and 9.1%, respectively, which decreased thereafter. The yearly incidence of severe cardiotoxicity was low (2.8%) and stable over time. In non-smoking patients with baseline LVEF > 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. CONCLUSIONS: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment.

Prediction of postnatal outcome in fetuses with congenital lung malformation: 2-year follow-up study.

OBJECTIVES: To identify, in fetuses with a congenital lung malformation (CLM), prenatal predictors of the need for postnatal respiratory support and the need for surgery by calculating the CLM volume ratio (CVR), and to evaluate the concordance between the prenatal appearance and the postnatal type of CLM. METHODS: This was an analysis of prenatal, perinatal and postnatal data from fetuses diagnosed with a CLM at the Erasmus University Medical Center - Sophia Children's Hospital in Rotterdam, The Netherlands, between January 2007 and December 2016. For all included fetuses, CVR was measured retrospectively on stored ultrasound images obtained at 18 + 1 to 24 + 6 weeks (US1), 25 + 0 to 29 + 6 weeks (US2) and/or 30 + 0 to 35 + 6 weeks' gestation (US3). Postnatal diagnosis of CLM was based on computed tomography or histology. Primary outcomes were the need for respiratory support within 24 h and surgery within 2 years after birth. RESULTS: Of the 80 fetuses with a CLM included in this study, 14 (18%) required respiratory support on the first postnatal day, and 17 (21%) required surgery within 2 years. Only the CVR at US2 was predictive of the need for respiratory support, with a cut-off value of 0.39. Four of 16 (25%) fetuses which showed full regression of the CLM prenatally required respiratory support within 24 h after birth. The CVR at US1, US2 and US3 was predictive of surgery within 2 years. Overall, the prenatal appearance of the CLM showed low concordance with the postnatal type. Prenatally suspected microcystic congenital pulmonary airway malformation (CPAM) was shown on computed tomography after birth to be congenital lobar overinflation in 15/35 (43%) cases. Respiratory support within 24 h after birth and surgical resection within 28 days after birth were needed in all cases of macrocystic CPAM. CONCLUSIONS: CVR can predict the need for respiratory support within 24 h after birth and for surgery within 2 years. Regression of a CLM prenatally does not rule out respiratory problems after birth. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

A new diagnostic work-up for defining anemia etiologies: a cohort study in patients ≥ 50 years in general practices.

BACKGROUND: To study etiologies of anemia using an extensive laboratory analysis in general practices. METHOD: An extensive laboratory analysis was performed in blood of newly diagnosed anemia patients aged ≥50 years from the general population in the city of Dordrecht area, the Netherlands. Eight laboratory-orientated etiologies of anemia were defined. Patients were assigned one or more of these etiologies on the basis of their test results. RESULTS: Blood of 4152 patients (median age 75 years; 49% male) was analyzed. The anemia etiology was unclear in 20%; a single etiology was established in 59%; and multiple etiologies in 22% of the patients. The most common etiologies were anemia of chronic disease (ACD) (54.5%), iron deficiency anemia (IDA) (19.1%) and renal anemia (13.8%). The most common single etiologies were IDA (82%) and ACD (68%), while the multiple etiologies most commonly included folic acid deficiency (94%) and suspected bone marrow disease (88%). Older age was associated with a lower incidence of IDA and a higher incidence of renal anemia. Mild anemia was more often associated with ACD and uncertain anemia, while severe anemia was mainly seen in patients with IDA. CONCLUSION: Extensive laboratory analysis in anemic patients from the general population helped clarify the etiology of anemia and revealed many various combinations of etiologies in a significant proportion of patients. Age, sex and the severity of anemia are predictive of the underlying etiology.

Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study).

OBJECTIVES: Overuse of broad-spectrum antibiotics in emergency departments (EDs) results in antibiotic resistance. We determined whether procalcitonin (PCT) -guided therapy can be used to reduce antibiotic regimens in EDs by investigating efficacy, safety and accuracy. METHODS: This was a non-inferiority multicentre randomized clinical trial, performed in two Dutch hospitals. Adult patients with fever ≥38.2°C (100.8°F) in triage were randomized between standard diagnostic workup (control group) and PCT-guided therapy, defined as standard workup with the addition of one single PCT measurement. The treatment algorithm encouraged withholding antibiotic regimens with PCT <0.5 µg/L, and starting antibiotic regimens at PCT ≥0.5 µg/L. Exclusion criteria were immunocompromised conditions, pregnancy, moribund patients, patients <72 h after surgery or requiring primary surgical intervention. Primary outcomes were efficacy, defined as number of prescribed antibiotic regimens; safety, defined as combined safety end point consisting of 30 days mortality, intensive-care unit admission, ED return visit within 2 weeks; accuracy, defined as sensitivity, specificity and area-under-the-curve (AUC) of PCT for bacterial infections. Non-inferiority margin for safety outcome was 7.5%. RESULTS: Between August 2014 and January 2017, 551 individuals were included. In the PCT-guided group (n = 275) 200 (73%) patients were prescribed antibiotic regimens, in the control group (n = 276) 212 (77%) patients were prescribed antibiotics (p 0.28). There was no significant difference in combined safety end point between the PCT-guided group, 29 (11%), and control group, 46 (16%) (p 0.16), with a non-inferiority margin of 0.46% (n = 526). AUC for confirmed bacterial infections for PCT was 0.681 (95% CI 0.633-0.730), and for CRP was 0.619 (95% CI 0.569-0.669). CONCLUSIONS: PCT-guided therapy was non-inferior in terms of safety, but did not reduce prescription of antibiotic regimens in an ED population with fever. In this heterogeneous population, the accuracy of PCT in diagnosing bacterial infections was poor. TRIAL REGISTRATION IN NETHERLANDS TRIAL REGISTER: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4949.

Unexpected mechanisms of resistance in Dutch Pseudomonas aeruginosa isolates collected during 14 years of surveillance.

Pseudomonas aeruginosa is one of the most important causes of infection in intensive care units (ICUs). It is intrinsically resistant to many antimicrobials and easily acquires additional resistance genes via horizontal gene transfer of mobile genetic elements. In this study, 1528 P. aeruginosa isolates obtained from a Dutch national surveillance programme between the years 1998-2011 were analysed for the presence of extended-spectrum ß-lactamase (ESBL) genes (blaCTX-M, blaSHV, blaTEM, blaBEL, blaPER, blaVEB and blaOXA-10) and metallo-ß-lactamase (MBL) genes (blaIMP, blaVIM and blaNDM). Of the ceftazidime-resistant isolates, 6.2% tested phenotypically positive for ESBL. Moreover, a Verona integron-encoded MBL (VIM) gene was found in 3.1% of isolates that were phenotypically resistant to imipenem and/or meropenem. Multilocus sequence typing (MLST) of ESBL-positive isolates indicated ST1216, ST111 and ST622, with all blaVIM-positive isolates belonging to the ST111 clone. Although the prevalence of ESBL and MBL phenotypes in this Dutch national surveillance collection of >1500 ICU P. aeruginosa isolates was very low, all VIM-producing isolates belonged to the high risk-associated, international, clonal complex CC111, and most ESBL-producing isolates belonged to clonal complexes known for their successful spread, e.g. CC111 and CC235. These data indicate that high-risk clones of P. aeruginosa were present in the Netherlands between 1998-2011 and probably spread unnoticed throughout Dutch hospitals.

[Humanization of Murine Monoclonal anti-hTNF Antibody: The F10 Story].

Tumor necrosis factor (TNF) is a proinflammatory cytokine implicated in pathogenesis of multiple autoimmune and inflammatory diseases. Anti-TNF therapy has revolutionized the therapeutic paradigms of autoimmune diseases and became one of the most successful examples of the clinical use of monoclonal antibodies. Currently, anti-TNF therapy is used by millions of patients worldwide. At the moment, fully human anti-TNF antibody Adalimumab is the best-selling anti-cytokine drug in the world. Here, we present a story about a highly potent anti-TNF monoclonal antibody initially characterized more than 20 years ago and further developed into chimeric and humanized versions. We present comparative analysis of this antibody with Infliximab and Adalimumab.

Effectiveness of various cleaning and disinfectant products on Clostridium difficile spores of PCR ribotypes 010, 014 and 027.

BACKGROUND: In healthcare facilities, Clostridium difficile infections spread by transmission of bacterial spores. Appropriate sporicidal disinfectants are needed to prevent development of clusters and outbreaks. In this study different cleaning/disinfecting wipes and sprays were tested for their efficacy against spores of distinctive C. difficile PCR ribotypes. METHODS: Four different products were tested; 1) hydrogen peroxide 1.5%; 2) glucoprotamin 1.5%; 3) a mixture of ethanol, propane and N-alkyl amino propyl glycine; and 4) a mixture of didecyldimonium chloride, benzalkonium chloride, polyaminopropyl, biguanide and dimenthicone as active ingredients. Tiles were contaminated with a test solution containing a concentration of 5x106CFU/ml spores of C. difficile strains belonging to PCR ribotypes 010, 014 or 027. The tiles were left to dry for an hour and then wiped or sprayed with one of the sprays or wipes as intended by the manufacturers. When products neutralized after 5 min, microbiological cultures and ATP measures were performed. RESULTS: Irrespective of the disinfection method, the microbial count log10 reduction of C. difficile PCR ribotype 010 was highest, followed by the reduction of C. difficile 014 and C. difficile 027. Overall, the wipes performed better than the sprays with the same active ingredient. On average, although not significantly, a difference in relative light units (RLU) reduction between the wipes and sprays was found. The wipes had a higher RLU log10 reduction, but no significant difference for RLU reduction was observed between the different C. difficile strains (p = 0.16). CONCLUSION: C. difficile spores of PCR ribotypes 014 and 027 strains are more difficult to eradicate than non-toxigenic PCR ribotype 010. In general, impregnated cleaning/disinfection wipes performed better than ready-to-use sprays. Wipes with hydrogen peroxide (1.5%) showed the highest bactericidal activity.

Changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation.

OBJECTIVE: Thyroid hormone concentrations can be disturbed during critical illness. Our aim was to determine changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: We included 21 ECMO-treated neonates. Age-specific s.d. scores (SDS) of free and total thyroxine (FT4; TT4), reverse and total triiodothyronine (rT3; TT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) were determined at six fixed time-points. Data were analyzed using general linear models. RESULTS: At baseline, mean SDS FT4 (-0.78, 95% CI: -1.37 to -0.19), TT4 (-1.97, 95% CI: -2.76 to -1.18), TT3 (-0.88, 95% CI: -1.13 to -0.63), TSH (-2.14, 95% CI: -2.93 to -1.35) and TBG (-3.52, 95% CI: -4.55 to -2.50) were low with high mean SDS rT3 (0.53, 95% CI: 0.28 to 0.78). One hour after start ECMO, TT4, TSH and TBG had further declined; 12 h after start ECMO TT3 had declined (all P<0.05). After this decline, mean SDS TSH increased to the baseline level 12 h after start ECMO (-2.50, 95% CI: -3.22 to -1.79), and was higher than baseline 48 h after start ECMO (-0.56, 95% CI: -1.29 to 0.17). This TSH increase was followed by increases in TT4 and TT3. FT4 remained constant within the normal range during ECMO. CONCLUSIONS: Thyroid hormone concentrations before ECMO were suggestive of non-thyroidal illness syndrome (NTIS). During ECMO, increases in TSH, TT4 and TT3 after an initial decline possibly reflect spontaneous restoration of the hypothalamic-pituitary-thyroid axis. FT4 remained constant within the normal range. This suggests that thyroxine therapy is not required during ECMO.

[A young man with green urine]. / Een man met groene urine na een val van de trap.

A 37-year-old male was admitted to the Intensive Care Unit with severe traumatic brain injury. Propofol, midazolam and sufentanil were administered. Two days after admittance, we observed a green discoloration of the urine. This is a rare and benign side effect of propofol.

Systematic Review and Meta-Analysis of the Impact of Computed Tomography-Assessed Skeletal Muscle Mass on Outcome in Patients Awaiting or Undergoing Liver Transplantation.

Liver transplant outcome has improved considerably as a direct result of optimized surgical and anesthesiological techniques and organ allocation programs. Because there remains a shortage of human organs, strict selection of transplant candidates remains of paramount importance. Recently, computed tomography (CT)-assessed low skeletal muscle mass (i.e. sarcopenia) was identified as a novel prognostic parameter to predict outcome in liver transplant candidates. A systematic review and meta-analysis on the impact of CT-assessed skeletal muscle mass on outcome in liver transplant candidates were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Nineteen studies, including 3803 patients in partly overlapping cohorts, fulfilled the inclusion criteria. The prevalence of sarcopenia ranged from 22.2% to 70%. An independent association between low muscle mass and posttransplantation and waiting list mortality was described in 4 of the 6 and 6 of the 11 studies, respectively. The pooled hazard ratios of sarcopenia were 1.84 (95% confidence interval 1.11-3.05, p = 0.02) and 1.72 (95% confidence interval 0.99-3.00, p = 0.05) for posttransplantation and waiting list mortality, respectively, independent of Model for End-stage Liver Disease score. Less-consistent evidence suggested a higher complication rate, particularly infections, in sarcopenic patients. In conclusion, sarcopenia is an independent predictor for outcome in liver transplantation patients and could be used for risk assessment.

A clinically weighted approach to outcome assessment in radial polydactyly.

UNLABELLED: Currently available outcome assessment systems for radial polydactyly are mainly based on expert opinion. The aim of this study was to develop an outcome assessment system based on clinical data. We performed linear regression analysis on data from a multicentre study of 121 patients with radial polydactyly types II, IV and VII to develop a clinically weighted outcome assessment system. Items were weighted according to their influence on overall functional and aesthetic outcome in the regression analysis. Active flexion, scar appearance and prominence at amputation site were the main items influencing overall functional and aesthetic outcome (ß = 0.393, ß = 0.326 and ß = 0.288, respectively). Palmar abduction, metacarpophalangeal joint deviation and nail appearance influenced overall functional and aesthetic outcome the least (ß = -0.002, ß = -0.104 and ß = 0.070, respectively). Our proposed assessment system for radial polydactyly reflects the way clinicians value individual aspects of outcome as determinants of overall outcome and helps guide future treatment and evaluation of outcome. LEVEL OF EVIDENCE: III.

Different characteristics of high and low transsphincteric fistulae.

AIM: Transsphincteric fistulae are classified as high or low. The aim of this observational study was to determine whether or not they have different characteristics. METHOD: A consecutive series of 300 patients with a transsphincteric fistula of cryptoglandular origin was studied. Two hundred patients with a high transsphincteric fistula underwent transanal advancement flap repair and 100 patients with a low transsphincteric fistula underwent fistulotomy or ligation of the intersphincteric fistula tract at the Division of Colon and Rectal Surgery, Erasmus MC, Rotterdam. Various patient and fistula characteristics were assessed. Data were analysed by means of logistic regression. RESULTS: Low transsphincteric fistulae occurred more frequently in females (43% low transsphincteric fistulae vs 30% high transsphincteric fistulae; P < 0.05). The internal opening of these fistulae was predominantly located anteriorly (76% vs 18% in high transsphincteric fistulae; P < 0.001). Mean age at surgery was lower in patients with a low transsphincteric fistula (42 vs 47 years; P < 0.001). In these patients an associated abscess was observed in 4% compared with 54% of those patients with a high transsphincteric fistula (P < 0.001). In multivariate analysis, the differences between high and low transsphincteric fistulae regarding location of their internal opening and the presence of associated abscesses remained significant (P < 0.001). CONCLUSION: Although not significant in multivariate analysis, low transsphincteric fistulae occur more frequently in younger patients and more often in females. These fistulae are predominantly located anteriorly and are rarely associated with an abscess. This was significant in univariate and multivariate analysis.

Cost-effectiveness of cervical cancer screening: cytology versus human papillomavirus DNA testing.

OBJECTIVE: To determine the most cost-effective screening programme for cervical cancer. DESIGN: Cost-effectiveness analysis from a societal perspective. SETTING: The Netherlands. POPULATION: Dutch women who have not been invited for human papillomavirus (HPV) vaccination. METHODS: We calibrated the microsimulation screening analysis (MISCAN) model to Dutch epidemiological data. We used this model to consider nine screening strategies that use: (i) cytological testing with cytology triage for borderline/mildly abnormal smears; (ii) HPV testing with cytology triage for HPV-positive smears; or (iii) cytological testing with HPV triage for borderline/mildly abnormal smears. For each strategy, we varied the number of screening rounds, the time interval, the age of the first screening, and the type of cytological testing (conventional or liquid-based cytology). MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) gained and costs from a societal perspective. RESULTS: Under the base-case assumptions, primary HPV testing with cytology triage is the most cost-effective strategy. Using cost-effectiveness thresholds of € 20,000 and € 50,000 per QALY gained yields optimal screening programmes with three and seven screening rounds, respectively. The results are sensitive to several uncertain model inputs, most importantly the costs of the HPV test. For women aged 32 years or younger, primary cytology screening is more cost-effective than primary HPV testing. CONCLUSIONS: Increasing the interval between screening rounds and changing the primary test from cytology to HPV testing can improve the effectiveness and decrease the costs of cervical cancer screening in the Netherlands.