OXA-48-Producing Uropathogenic Escherichia coli Sequence Type 127, the Netherlands, 2015-2022.

During 2015-2022, a genetic cluster of OXA-48-producing uropathogenic Escherichia coli sequence type 127 spread throughout the Netherlands. The 20 isolates we investigated originated mainly from urine, belonged to Clermont phylotype B2, and carried 18 genes encoding putative uropathogenicity factors. The isolates were susceptible to first-choice antimicrobial drugs for urinary tract infections.

Evaluation of 18 commercial serological assays for the detection of antibodies against SARS-CoV-2 in paired serum samples.

A variety of serological tests have been developed to detect the presence of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the performance of 18 commercially available SARS-CoV-2 antibody assays. Early (6-8 days after the start of symptoms) and late sera (>14 days) from ICU patients (n=10 and n=16, respectively) and healthcare workers (n=5 and n=9, respectively) were included. Additionally, 22 sera were included to detect potential cross-reactivity. Test characteristics were determined for the 18 assays. In >14 days samples, the Vircell IgG and Wantai Ig ELISAs had superior sensitivity compared to the other ELISAs (96%). Furthermore, the Roche Ig, the Epitope Diagnostics IgM, Wantai IgM, Euroimmun IgG, and IgA all showed a specificity of 100%. The POCTs of Boson Biotech and ACRO Biotech showed the highest sensitivities: 100% and 96% (83.5-99.8), respectively. The POCT of Orient Gene Biotech, VOMED Diagnostics, and Coris-Bioconcept showed highest specificities (100%). For the IgM and IgA assays, the Euroimmun IgA test showed the highest sensitivity in early samples: 46.7% (23.5-70.9) to 53.3% (29.1-76.5). In general, all tests performed better in patients with severe symptoms (ICU patients). We conclude that the Wantai Ig and Vircell IgG ELISAs may be suitable for diagnostic purposes. The IgM/IgA tests performed poorer than their IgG/Ig counterparts but may have a role in diagnoses of SARS-CoV-2 in a population in which the background seroprevalence of IgG high, and IgM and/or IgA may distinguish between acute or past infection.

Calcium intake, levels and supplementation and effect modification by genetic variation of calcium homeostasis on the risk of colorectal cancer: the Rotterdam study.

OBJECTIVES: Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were inconclusive. In this study, we evaluated whether calcium intake from diet and supplements, as well as the calcium levels itself, were associated with the CRC risk in middle-aged and older individuals. Also, we evaluated whether these associations were modified by genetic variation of calcium homeostasis. DESIGN: This study was embedded in the Rotterdam study, a prospective cohort study among adults aged 55 years and older without CRC at baseline, from the Ommoord district of Rotterdam, The Netherlands (N = 10 941). Effect modification by a predefined polygenetic risk score (PRS) from seven loci known to be associated with calcium concentrations, was evaluated. RESULTS: The incidence rate of CRC in the study population was 2.9 per 1000 person-years. Relative to the recommended dietary calcium intake, only higher than the recommended dietary calcium intake (≥1485 mg/day) was associated with a reduced risk of CRC [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.44-1.00]. No significant associations were found for calcium supplementation and only in the subgroup analysis, albumin-adjusted calcium levels were associated with an increased risk of CRC (HR = 1.11; 95% CI, 1.00-1.23). PRS showed effect modification in the association between calcium intake and CRC (P for interaction = 0.08). After stratification of PRS into low, intermediate and high, we found a lower CRC risk for low-weighted PRS per increase in calcium intake. CONCLUSION: There is no consistent association between calcium indices on CRC. However, the association between calcium intake and CRC may be modified by genetic variation associated with serum calcium concentrations that deserves further replication in other studies with different population.

The systemic immune-inflammation index is associated with an increased risk of incident cancer-A population-based cohort study.

Several studies found that the systemic immune-inflammation index (SII) is a prognostic factor for mortality in patients with solid tumors. It is unknown whether an increased SII in generally healthy individuals reflects a risk for developing cancer. Our objective was to investigate the association between the SII and incident cancers in a prospective cohort study. Data were obtained from the Rotterdam Study; a population-based study of individuals aged ≥45 years, between 2002 and 2013. The SII at baseline was calculated from absolute blood counts. The association between the SII and the risk of any solid incident cancer during follow-up was assessed using Cox proportional hazard models. Individuals with a prior cancer diagnosis were excluded. Data of 8,024 individuals were included in the analyses. The mean age at baseline was 65.6 years (SD 10.5 years) and the majority were women. During a maximum follow-up period of 10.7 years, 733 individuals were diagnosed with cancer. A higher SII at baseline was associated with a 30% higher risk of developing a solid cancer (HR of 1.30 [95% CI; 1.11-1.53]), after adjustment for age, sex, socioeconomic status, smoking, BMI and type 2 diabetes. The absolute cumulative 10-year cancer risk increased from 9.7% in the lowest quartile of SII to 14.7% in the highest quartile (p-value = 0.009). The risk of developing cancer was persistent over time and increased for individuals with the longest follow-up. In conclusion, a high SII is a strong and independent risk indicator for developing a solid cancer.

Trends of prescribing antimicrobial drugs for urinary tract infections in primary care in the Netherlands: a population-based cohort study.

OBJECTIVE: Urinary tract infections (UTIs) are an important reason to consult a general practitioner (GP). Here, we describe antimicrobial drug prescribing patterns for UTIs by GPs in relation to the Dutch primary care guidelines. METHODS: We conducted a population-based cohort study in the Dutch Integrated Primary Care Information (IPCI)database, which encompasses approximately 2.5 million patients. All patients aged ≥12 years with at least 1 year of follow-up from 1996 to 2014 were extracted from the database. The number of prescriptions and choice of drug type were investigated over time and in different age categories. The choice of antimicrobial drug classes for UTIs and the duration of nitrofurantoin use in women were compared with the Dutch primary care guidelines of 1989, 1999, 2005 and 2013. RESULTS: The source population comprised 1 755 085 patients who received 2 019 335 antimicrobial drug prescriptions; 401 655 (35.1%) prescriptions were for UTIs (45.2% in women and 12.6% in men). The proportion of prescriptions for UTIs within all prescriptions with an indication code increased from 5.2% in 1996 to 14% in 2014 in men and from 28% in 1996 to 50% in 2014 in women. In men, UTIs were most frequently treated with fluoroquinolones during the entire study period, whereas fluoroquinolones were only advised as first choice in the latest guideline of 2013. In women, UTIs were increasingly (p<0.05) treated with nitrofuran derivatives with a statistically significant difference after implementation of the guideline of 2005. Compliance to the advised duration of nitrofurantoin prescriptions in women has increased since the guideline of 2005. CONCLUSIONS: Antimicrobial drug prescribing for UTIs seemed to have increased over time. Prescribing in line with the UTI guidelines increased with regard to choice and duration of antimicrobial drugs. We showed that databases like IPCI, in which prescription and indication are monitored, can be valuable antibiotic stewardship tools.

Animal foods and postmenopausal breast cancer risk: a prospective cohort study.

The role of diet on breast cancer risk is not well elucidated but animal food sources may play a role through, for example, the pathway of the insulin-like growth factor 1 system or cholesterol metabolism. The aim of this study was to evaluate the association between animal foods and the risk of postmenopausal breast cancer. This study was embedded in the Rotterdam Study, a population-based prospective cohort study of subjects aged 55 years and over (61 % female). Dietary intake of different animal foods was assessed at baseline using a validated FFQ and adjusted for energy intake using the residual method. We performed Cox proportional hazards modelling to analyse the association between the intake of the different food sources and breast cancer risk after adjustment for socio-demographic, lifestyle and metabolic factors. During a median follow-up of 17 years, we identified 199 cases of breast cancer (6·2 %) among 3209 women. After adjustment for multiple confounders, no consistent association was found between the intake of red meat intake, poultry, fish or dairy products and breast cancer risk. However, we found that egg intake was significantly associated with a higher risk of breast cancer (hazard ratioQ4 v. Q1: 1·83; 95 % CI 1·20, 2·79; Ptrend=0·01). In conclusion, this study found that dietary egg intake but no other animal foods was associated with a higher risk of postmenopausal breast cancer. Further research on the potential mechanisms underlying this association is warranted.

Fracture incidence and secular trends between 1989 and 2013 in a population based cohort: The Rotterdam Study.

Fracture incidence needs to be evaluated over time to assess the impact of the enlarging population burden of fractures (due to increase in lifespan) and the efficacy of fracture prevention strategies. Therefore, we aimed to evaluate the association of femoral neck bone mineral density (FN-BMD) measured using dual-energy X-ray absorptiometry (DXA) at baseline with fracture risk over a long follow-up time period. Incident non-vertebral fractures were assessed in 14,613 individuals participating in the Rotterdam Study with up to 20 years of follow-up. During a mean follow-up of 10.7 ±â€¯6.2 years, 2971 (20.3%) participants had at least one incident non-vertebral fracture. The risk for any non-vertebral fracture was 1.37 (95% Confidence Interval (CI): 1.25-1.49) and 1.42 (95%CI: 1.35-1.50) for men and women, respectively. The majority (79% in men and 75% in women) of all fractures occurred among participants a normal or osteopenic T-score. The incidence rates per 1000 person-years for the most common fractures were 5.3 [95%CI: 5.0-5.7] for hip, 4.9 [95%CI: 4.6-5.3] for wrist and 2.3 [95%CI: 2.0-2.5] for humerus. To examine the predictive ability of BMD through follow-up time we determined fracture hazard ratios (HR) per standard deviation decrease in femoral neck BMD across five year bins. No differences were observed, with a HR of 2.5 (95%CI: 2.0-3.1) after the first 5 years, and of 1.9 (95%CI: 1.1-3.3) after 20 years. To assess secular trends in fracture incidence at all skeletal sites we compared participants at an age of 70-80 years across two time periods: 1989-2001 (n = 2481, 60% women) and 2001-2013 (n = 2936, 58% women) and found no statistically significant difference (p < 0.05) between fracture incidence rates (i.e., incidence of non-vertebral fractures of 26.4 per 1000 PY [95%CI: 24.4-28.5]) between 1989 and 2001, and of 25.4 per 1000 PY [95%CI: 23.0-28.0] between 2001 and 2013. In conclusion, BMD is still predictive of future fracture over a long period of time. While no secular changes in fractures rates seem to be observed after a decade, the majority of fractures still occur above the osteoporosis threshold, emphasizing the need to improve the screening of osteopenic patients.

Risk factors for resistance to ciprofloxacin in community-acquired urinary tract infections due to Escherichia coli in an elderly population.

BACKGROUND: Antimicrobial resistance to ciprofloxacin is rising worldwide, especially in bacteria causing urinary tract infections (UTIs). Prudent use of current antibiotic drugs is therefore necessary. OBJECTIVES: We analysed (modifiable) risk factors for ciprofloxacin-resistant Escherichia coli. METHODS: Urinary cultures of UTIs caused by E. coli were collected from participants in the Rotterdam Study, a prospective cohort study in an elderly population, and analysed for susceptibility to ciprofloxacin. Multivariate logistic regression was performed to investigate several possible risk factors for resistance. RESULTS: Ciprofloxacin resistance in 1080 E. coli isolates was 10.2%. Multivariate analysis showed that higher age (OR 1.03; 95% CI 1.00-1.05) and use of two (OR 5.89; 95% CI 3.45-10.03) and three or more (OR 3.38; 95% CI 1.92-5.97) prescriptions of fluoroquinolones were associated with ciprofloxacin resistance, while no association between fluoroquinolone use more than 1 year before culture and ciprofloxacin resistance could be demonstrated. Furthermore, a high intake of pork (OR 3.68; 95% CI 1.36-9.99) and chicken (OR 2.72; 95% CI 1.08-6.85) and concomitant prescription of calcium supplements (OR 2.51; 95% CI 1.20-5.22) and proton pump inhibitors (OR 2.04; 95% CI 1.18-3.51) were associated with ciprofloxacin resistance. CONCLUSIONS: Ciprofloxacin resistance in community-acquired UTI was associated with a high intake of pork and chicken and with concomitant prescription of calcium supplements and proton pump inhibitors. Modification of antibiotic use in animals as well as temporarily stopping the prescription of concomitant calcium and proton pump inhibitors need further evaluation as strategies to prevent ciprofloxacin resistance.

Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression: a longitudinal pilot study.

Electroconvulsive therapy (ECT) is the most potent biological therapy in depression. Animal studies suggest that ECT acts via neuroplasticity effects on limbic structures involved in the pathophysiology of depression but in vivo evidence at the human system level is scarce. Therefore, the aim of the present study was to investigate the effect of ECT on hippocampus and amygdala volume in 15 antidepressant-free patients with treatment refractory depression (seven males, range 42-63 years). ECT treatment was successful as indexed by a significant decrease in depressive symptoms (t14=13.6; p<0.001). Analysis of normalized volumetric data before and after ECT treatment revealed a significant volume increase of both hippocampus and amygdala (minimum p<0.005) with no evidence for a change in global brain volume. Though this change in volume cannot be clearly related to treatment effects, ECT is associated with broader neurotrophic effects other than mere adult neurogenesis in the hippocampus, which has been previously suggested as a core mechanism on the basis of animal data.

The concentration of anticitrullinated protein antibodies in serum and synovial fluid in relation to total immunoglobulin concentrations.

BACKGROUND: Anticitrullinated protein antibodies (ACPA) are one of the best predictors for the development of rheumatoid arthritis. Nonetheless, relatively little information is present on the absolute concentration of ACPA in relation to total immunoglobulin (Ig) concentrations. Such information would be of relevance to compare ACPA levels to other antibody levels. Here, we estimated the relative abundance of ACPA Ig in serum and synovial fluid using a quantitative approach. METHODS: ACPA were purified using HiTrap Streptavidin columns coupled with biotinylated cyclic citrullinated peptide (CCP2). Total Ig and anti-CCP2 isotype reactivities were measured by ELISA. RESULTS: ACPA were successfully isolated as substantial antibody amounts were eluted from sera of ACPA-positive patients and neglectable antibody amounts were eluted from sera of ACPA-negative patients. Up to 1 in 80 IgG-molecules were estimated to be ACPA. Strikingly, IgM-ACPA was most abundant in synovial fluid (with the highest enrichment in the range of one IgM-ACPA for every eight IgM-antibodies). CONCLUSIONS: ACPA-IgG levels are estimated to be within the range of peak levels of protective antibody responses against recall antigens. IgM-ACPA is abundantly present in synovial fluid, suggesting the presence of a continuous ongoing autoimmune response in the synovial compartment.

Electroconvulsive therapy in a terminally ill patient: when every day of improvement counts.

Electroconvulsive therapy (ECT) is seldom used in a palliative setting. Although literature on the application of ECT in terminally ill patients is sparse, ECT may be useful to rapidly improve the quality of life in these patients. We present the case of a 71-year-old man with metastasized pancreas carcinoma complicated by severe depression. After 3 ECT sessions, the communication between the patient and his family in the last moments of his life improved. We conclude that ECT should be considered to treat mood disorders in terminally ill patients when every day of improvement counts.