Perceived barriers and solutions by generalist physicians to work towards timely young-onset dementia diagnosis.

Objectives: Timely diagnosis of young-onset dementia (YOD) is an important prerequisite to initiate appropriate support. However, YOD diagnosis is often late. We aimed to explore the perspectives of referring general practitioners and occupational physicians, to better understand their barriers to YOD diagnosis and reveal potential solutions to facilitate timely diagnosis.Methods: We conducted 16 semi-structured qualitative interviews with general practitioners and occupational physicians in the Netherlands. Inductive thematic analysis was applied to the transcripts with a team including researchers from various (clinical) backgrounds.Results: Thematic analysis revealed three themes related to: (1) disease characteristics that hinder YOD recognition, being the low incidence and the fact that they mimic other prevalent conditions like burn-out and depression; (2) physicians' attitudes that delay YOD diagnosis, as fear of mis-diagnosis and therapeutic nihilism; and (3) proposed solutions to navigate the challenging YOD diagnostic trajectory including monitoring people with depression and burn-out to consider YOD when recovery stagnates, and more effective interprofessional collaboration.Conclusion: In this study, referring physicians confirmed barriers known to YOD diagnosis and suggested potential solutions to improve YOD diagnosis. Future prospective studies in people with a primary diagnosis of depression or burn-out may show whether these interventions are potentially effective.

The bumpy ride to a medical PhD degree: a qualitative study on factors influencing motivation.

INTRODUCTION: In parallel with a tremendous increase in medical PhD enrolments, concerns have risen about PhD candidates' poor well-being, increasing attrition rates for PhD programmes, and, eventually, a decline in clinician-scientists. According to the Self-Determination Theory, autonomous motivation is strongly linked to positive aspects of well-being and other positive outcomes such as study completion and success. In this way, motivation has a pivotal role in successful completion of medical doctoral programmes. In this study we explored factors affecting motivation during the PhD journey and aimed to contribute to engaging doctoral education environments, and, eventually, a sustainable clinician-scientist workforce. METHODS: This constructivist qualitative interview study was conducted among ten medical PhD candidates in the final phase of their PhD. We used timeline assisted interviews to identify meaningful experiences throughout their PhD journey. Thematic analyses as an iterative process resulted in overarching themes. RESULTS: We identified six themes influencing autonomous and controlled motivation along the challenging PhD journey: (1) Initial motivation to start a PhD matters; (2) Autonomy as a matter of the right dose at the right time; (3) PhD as proof of competence and/or learning trajectory?; (4) It takes two to tango; (5) Peers can make or break your PhD; (6) Strategies to stay or get back on track. CONCLUSION: This study revealed factors that contribute positively and/or negatively to autonomous and controlled motivation. Some factors impacted motivation differently depending on the PhD phase and individual strategies. Additionally, some factors could coincide and change from positive to negative and vice versa, showing that a successful journey cannot simply be reduced to an absence of negative experiences.

Perspectives of patients with colorectal cancer liver metastases on e-consultation in transmural care: a qualitative study : Is privacy really an issue?

BACKGROUND: Comprehensive cancer networks have been established to deliver high-quality care for patients with cancer. Logistic challenges are faced, when patients need to be referred for specialized treatments. Despite strengthened privacy legislations, digital platforms are increasingly used to consult specialists from dedicated liver centers or refer patients with colorectal cancer liver metastases (CRLM) for local treatment strategies. This qualitative study aimed to explore the perspectives of patients with CRLM regarding e-consultation of transmural specialists. METHODS: A focus group study was conducted. Patients referred from regional hospitals to an academic liver center for treatment of CRLM were asked to participate. Focus group discussions were audio-recorded and transcribed verbatim. A thematic content analysis of data was conducted, comprising open, axial, and selective coding of the transcripts. The consolidated criteria for reporting qualitative research (COREQ) were used. RESULTS: Two focus groups were held, involving 11 patients and 8 relatives. Three major themes were identified with regard to e-consultation in transmural care: 'data management', 'expertise', and 'information and coordination'. Confidence in the expertise of physicians appeared most important during the course of treatment, as patients experienced uncertainty after diagnosis of cancer. Despite the privacy risks, use of digital communication platforms to contact experts in the field were strongly endorsed to improve eligibility for potentially curative treatment. Moreover, e-consultation of specialists may reduce waiting times, due to effective coordination of care. CONCLUSION: Initiatives to improve medical data transfer between care providers were encouraged to achieve effective coordination of oncological care. The potential hazard of privacy violation associated with digital data exchange is accepted by patients and their relatives, provided that use of digital data improves patient's own health care, research or education.

Positive health during the COVID-19 pandemic: a survey among community-dwelling older individuals in the Netherlands.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) reached the Netherlands in February 2020. To minimize the spread of the virus, the Dutch government announced an "intelligent lockdown". Older individuals were urged to socially isolate completely, because they are at risk of a severe disease course. Although isolation reduces the medical impact of the virus, the non-medical impact should also be considered. AIM: To investigate the impact of COVID-19 pandemic and associated restrictive measures on the six dimensions of Positive Health in community-dwelling older individuals living in the Netherlands, and to identify differences within subgroups. METHODS: In May/June 2020, community-dwelling older individuals aged ≥ 65 years completed an online survey based on Huber's model of Positive Health. Positive Health was measured regarding the appreciation of the six dimensions (categorized as poor/satisfactory/excellent) and a comparison with a year before (categorized as decreased/unchanged/increased) using frequencies (%) and a chi-square test. RESULTS: 834 older individuals participated (51% women, 38% aged ≥ 76 years, 35% living alone, 16% self-rated poor health). Most respondents assessed their bodily functions, mental well-being and daily functioning as satisfactory, their meaningfulness and quality of life (QoL) as excellent, and their social participation as poor. 12% of the respondents reported a deterioration of 4-6 dimensions and 73% in 1-3 dimensions, compared to the past year. Deterioration was most frequently experienced in the dimension social participation (73%), the dimension mental well-being was most frequently improved (37%) and quality of life was in 71% rated as unchanged. Women more often observed a deterioration of 4-6 dimensions than men (15% vs. 8%, p = 0.001), and individuals with self-rated poor health more often than individuals with self-rated good health (22% vs. 10%, p < 0.001). Older individuals living alone experienced more frequently a decrease in meaningfulness compared to older individuals living together. CONCLUSION: The COVID-19 pandemic and associated restrictive measures had a substantial impact on all six dimensions of Positive Health in community-dwelling older individuals, especially in women, respondents living alone and respondents with self-rated poor general health.

Predicting return to work among patients with colorectal cancer.

BACKGROUND: The increase in prevalence of colorectal cancer among young patients coupled with an older retirement age in developed countries means that more patients are being diagnosed with colorectal cancer while still at work. The aim of this study was to develop prediction models for return to work by 1 and 2 years after the start of sick leave. METHODS: This was a retrospective registry-based cohort study of data from a nationwide occupational health service in the Netherlands. Only employed patients with colonic or rectal cancer treated with curative intent were included. Two predictor variable models were developed using multivariable logistic regression with backward selection. Calibration, discrimination and explained variance were used to assess model performance, and internal validation by bootstrapping was performed. RESULTS: Median time to return to work for 317 included patients was 423 (95 per cent c.i. 379 to 467) days. Two-thirds of patients had returned to work by 2 years after the start of the sick leave. Presence of metastases, adjuvant treatment, stoma, emotional distress and postoperative complications were predictors of not returning to work in the 1-year model. In the 2-year model, presence of metastases, emotional distress, postoperative complications, company size and the trajectory of the return-to-work process were predictors. CONCLUSION: Almost 70 per cent of patients with colorectal cancer in this population returned to work within 2 years after the start of sick leave. The models can be used to guide patients early in colorectal cancer treatment about the likelihood of returning to work, and to identify and modify barriers that could facilitate this.

ANTECEDENTES: El aumento de la prevalencia del cáncer colorrectal (colorectal cancer, CCR) en pacientes jóvenes, junto con una edad de jubilación más avanzada en los países desarrollados, significa un mayor número de pacientes en edad laboral diagnosticados de CCR. El objetivo de este estudio fue desarrollar modelos de predicción del regreso al trabajo uno y dos años después del inicio de la baja por enfermedad para el tratamiento de CCR. MÉTODOS: Se trata de un estudio de cohortes retrospectivo basado en el registro de datos nacionales de salud laboral en los Países Bajos. Solo se incluyeron pacientes con cáncer de colon o recto tratados con intención curativa. Se desarrollaron dos modelos de variables de predicción utilizando regresión logística multivariante con selección de variables hacia atrás. Para evaluar el rendimiento del modelo se utilizaron la calibración, la discriminación y la varianza explicada y se realizó la validación interna mediante bootstrap. RESULTADOS: La mediana de tiempo de regreso al trabajo de 317 pacientes incluidos fue de 423 días (i.c. del 95%: 378,6-467,4). Dos tercios de los pacientes habían regresado al trabajo dos años después del inicio del período de baja por enfermedad. La presencia de metástasis, el tratamiento adyuvante, el estoma, la angustia emocional y las complicaciones postoperatorias fueron factores predictivos de no volver a trabajar en el modelo de un año. En el modelo de dos años, la presencia de metástasis, la angustia emocional, las complicaciones postoperatorias, el tamaño de la empresa y la trayectoria del proceso de retorno al trabajo fueron factores predictores del regreso laboral. CONCLUSIÓN: Casi el 70% de los pacientes con CCR en esta población volvieron a trabajar dentro de los dos años posteriores al inicio del periodo de baja por enfermedad. Los modelos se pueden usar para guiar a los pacientes con CCR al inicio de su tratamiento sobre su probabilidad de regresar al trabajo, así como para identificar y modificar las barreras que podrían facilitarlo.

Longitudinal bone microarchitectural changes are best detected using image registration.

Longitudinal studies of bone using high-resolution medical imaging may result in non-physiological measurements of longitudinal changes. In this study, we determined that three-dimensional image processing techniques best capture realistic longitudinal changes in bone density and should therefore be used with high-resolution imaging when studying bone changes over time. INTRODUCTION: The purpose of this study was to determine which longitudinal analysis technique (no registration (NR), slice-match (SM) registration, or three-dimensional registration (3DR)) produced the most realistic longitudinal changes in a 3-year study of bone density and structure using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: We assessed HR-pQCT scans of the distal radius and tibia for men and women (N = 40) aged 55-70 years at baseline and 6, 12, 24, and 36 months. To evaluate which longitudinal analysis technique (NR, SM, or 3DR) best captured physiologically reasonable 3-year changes, we calculated the standard deviation of the absolute rate of change in each bone parameter. The data were compared between longitudinal analysis techniques using repeated measures ANOVA and post hoc analysis. RESULTS: As expected, both SM and 3DR better captured physiological longitudinal changes than NR. At the tibia, there were no differences between SM and 3DR; however, at the radius where precision was lower, 3DR produced better results for total bone mineral density. CONCLUSIONS: At least SM or 3DR should be implemented in longitudinal studies using HR-pQCT. 3DR is preferable, particularly at the radius, to ensure that physiological changes in bone density are observed.

Active sculpting of colloidal crystals.

The development of colloidal particles that can become self-propelled when exposed to a source of light of a given frequency represents one of the most exciting new developments in the field of active matter. In this paper, we perform numerical simulations to explore several properties of crystalline colloidal aggregates in the presence of such external light fields. We show how permanent gaps of tunable size can be carved into these crystals as a result of a solid-gas transition that occurs above a threshold light intensity. We compare this phenomenon to that occurring in a parent system obtained by replacing self-propulsion with an effective temperature and discuss the main differences between the two setups. Finally, we show how moving the light field across a solid-fluid boundary allows us to transfer or transport the fluid component into or across the solid one. We discuss the dynamics of this process and set limits associated with its performance.

Cancer survivors' needs during various treatment phases after multimodal treatment for colon cancer - is there a role for eHealth?

BACKGROUND: More colon cancer patients are expected to fully recover after treatment due to earlier detection of cancer and improvements in general health- and cancer care. The objective of this study was to gather participants' experiences with full recovery in the different treatment phases of multimodal treatment and to identify their needs during these phases. The second aim was to propose and evaluate possible solutions for unmet needs by the introduction of eHealth. METHODS: A qualitative study based on two focus group discussions with 22 participants was performed. The validated Supportive Care Needs Survey and the Cancer Treatment Survey were used to form the topic list. The verbatim transcripts were analyzed with Atlas.ti. 7th version comprising open, axial and selective coding. The guidelines of the consolidated criteria for reporting qualitative research (COREQ) were used. RESULTS: Experiences with the treatment for colon cancer were in general positive. Most important unmet needs were 'receiving information about the total duration of side effects', 'receiving information about the minimum amount of chemo needed to overall survival' and 'receiving a longer aftercare period (with additional attention for psychological guidance)'. More provision of information online, a chat function with the oncological nurse specialist via a website, and access to scientific articles regarding the optimal dose of chemotherapy were often mentioned as worthwhile additions to the current health care for colon cancer. CONCLUSIONS: Many of the unmet needs of colon cancer survivors occur during the adjuvant treatment phase and thereafter. To further optimize recovery and cancer care, it is necessary to have more focus on these unmet needs. More attention for identifying patients' problems and side-effects during chemotherapy; and identifying patients' supportive care needs after finishing chemotherapy are necessary. For some of these needs, eHealth in the form of blended care will be a possible solution.

Behavior and Evolution of Young ONset Dementia part 2 (BEYOND-II) study: an intervention study aimed at improvement in the management of neuropsychiatric symptoms in institutionalized people with young onset dementia.

ABSTRACTBackground:Both neuropsychiatric symptoms (NPS) and psychotropic drug use (PDU) are common in institutionalized People with Young Onset Dementia (PwYOD) and can produce negative outcomes such as reduced quality of life and high workload. In community-dwelling PwYOD, NPS are found to be associated with unmet care needs. This emphasizes the importance of a care program for the management of NPS in institutionalized PwYOD that also addresses unmet care needs and PDU. The objectives of the Behavior and Evolution of Young ONset Dementia part 2 (BEYOND-II) study are to develop a care program for the management of NPS in institutionalized PwYOD and to evaluate its effectiveness. METHODS: The care program consists of an educational program combined with an intervention to manage NPS with the following five steps: the evaluation of psychotropic drug prescription, detection, analysis (including the detection of unmet needs), treatment and the evaluation of NPS. A stepped wedge design will be used to evaluate its effectiveness. The primary outcomes are agitation and aggression and other NPS. The secondary outcomes are PDU, quality of life, the workload of nursing staff and job satisfaction. Additionally, a process analysis and a cost-consequence analysis will be conducted. CONCLUSIONS: The study protocol of the Beyond-II study describes the development, implementation and evaluation of a care program for the management of NPS in institutionalized PwYOD. This care program provides a structured method for the management of NPS, in which unmet needs and PDU are also addressed.

Endoscopic ultrasound guided versus surgical transrectal drainage of pelvic abscesses.

BACKGROUND: Pelvic abscesses are common but only small case series reporting outcome of either endoscopic ultrasound (EUS) guided or surgical transrectal drainage have been reported. METHODS: We performed a retrospective consecutive cohort study, assessing effectivity and safety of EUS guided or surgical transrectal drainage of previously untreated pelvic abscesses from all causes, diagnosed using CT scan between 09/2010 and 06/2014 in a Dutch teaching hospital. RESULTS: Forty-six patients with comparable demographics, apart from stoma presence (p = .016), were included. The success rate after a single intervention was 83% in the EUS guided compared to 48% in the surgical transrectal drainage group (p = .013). However, the mean duration of drainage was threefold in the EUS group [42 versus 13 days (p = .001)]. The length of stay in hospital was similar for both EUS and surgical group [24 versus 20 days (p = .56)] as was abscess resolution during follow-up [78% versus 74%]. We recorded a total of 12 anastomotic leaks [3 versus 9]. In the occurrence of leakage, only one stoma was finally closed in each group. CONCLUSION: EUS guided and surgical transrectal drainage of pelvic abscesses from any cause are safe, nonetheless EUS guided drainage(if feasible) seems more effective after a single treatment, with high overall cure rates.

Improved estimation of MR relaxation parameters using complex-valued data.

PURPOSE: In MR image analysis, T1 , T2 , and T2* maps are generally calculated using magnitude MR data. Without knowledge of the underlying noise variance, parameter estimates at low signal to noise ratio (SNR) are usually biased. This leads to confounds in studies that compare parameters across SNRs and or across scanners. This article compares several estimation techniques which use real or complex-valued MR data to achieve unbiased estimation of MR relaxation parameters without the need for additional preprocessing. THEORY AND METHODS: Several existing and new techniques to estimate relaxation parameters using complex-valued data were compared with widely used magnitude-based techniques. Their bias, variance and processing times were studied using simulations covering various aspects of parameter variations. Validation on noise-degraded experimental measurements was also performed. RESULTS: Simulations and experiments demonstrated the superior performance of techniques based on complex-valued data, even in comparison with magnitude-based techniques that account for Rician noise characteristics. This was achieved with minor modifications to data modeling and at computational costs either comparable to or higher ( ≈two fold) than magnitude-based estimators. Theoretical analysis shows that estimators based on complex-valued data are statistically efficient. CONCLUSION: The estimation techniques that use complex-valued data provide minimum variance unbiased estimates of parametric maps and markedly outperform commonly used magnitude-based estimators under most conditions. They additionally provide phase maps and field maps, which are unavailable with magnitude-based methods. Magn Reson Med 77:385-397, 2017. © 2016 Wiley Periodicals, Inc.

Post-Colonoscopy Complications: A Systematic Review, Time Trends, and Meta-Analysis of Population-Based Studies.

OBJECTIVES: Many studies around the world addressed the post-colonoscopy complications, but their pooled prevalence and time trends are unknown. We performed a systematic review and meta-analysis of population-based studies to examine the pooled prevalence of post-colonoscopy complications ("perforation", "bleeding", and "mortality"), stratified by colonoscopy indication. Temporal variability in the complication rate was assessed. METHODS: We queried Pubmed, Embase, and the Cochrane library for population-based studies examining post-colonoscopy complications (within 30 days), performed from 2001 to 2015 and published by 1 December 2015. We determined pooled prevalence of perforations, post-colonoscopy bleeding, post-polypectomy bleeding, and mortality. RESULTS: We retrieved 1,074 studies, of which 21 met the inclusion criteria. Overall, pooled prevalences for perforation, post-colonoscopy bleeding, and mortality were 0.5/1,000 (95% confidence interval (CI) 0.4-0.7), 2.6/1,000 (95% CI 1.7-3.7), and 2.9/100,000 (95% CI 1.1-5.5) colonoscopies. Colonoscopy with polypectomy was associated with a perforation rate of 0.8/1,000 (95% CI 0.6-1.0) and a post-polypectomy bleeding rate of 9.8/1,000 (95% CI 7.7-12.1). Complication rate was lower for screening/surveillance than for diagnostic examinations. Time-trend analysis showed that post-colonoscopy bleeding declined from 6.4 to 1.0/1,000 colonoscopies, whereas the perforation and mortality rates remained stable from 2001 to 2015. Overall, considerable heterogeneity was observed in most of the analyses. CONCLUSIONS: Worldwide, the post-colonoscopy complication rate remained stable or even declined over the past 15 years. The findings of this meta-analysis encourage continued efforts to achieve and maintain safety targets in colonoscopy practice.

Temporal trends and variability of colonoscopy performance in a gastroenterology practice.

BACKGROUND AND STUDY AIM: Quality measures for colonoscopy are operator dependent and vary. It is unclear whether quality measures change over time. In this study, time-dependent variation in colonoscopy performance was examined in a gastroenterology practice. PATIENTS AND METHODS: Colonoscopy and histopathology records that were collected at three hospitals (one university and two non-university hospitals) over three time periods (2007, 2010, and 2013) were reviewed. Data from colonoscopists performing at least 100 procedures per year were analyzed. Inter-colonoscopist variation in performance (i. e. adjusted cecal intubation rate [aCIR], adenoma detection rate [ADR], advanced ADR, mean adenomas per procedure [MAP], proximal ADR, nonpolypoid ADR, and serrated polyp detection rate) were examined using coefficients of variation. Logistic regression analyses were also performed, adjusting for covariates. RESULTS: A total of 23 colonoscopists performing 6400 procedures were included. Overall, the mean aCIR, ADR, MAP, and proximal ADR improved significantly over time, from 91.9 %, 22.5 %, 0.37, and 10.2 % in 2007 to 95.3 %, 25.8 %, 0.45, and 13.4 %, respectively, in 2013 (P < 0.05). The inter-colonoscopist variation in ADR decreased from 37 % in 2007 to 15 % in 2013 (P < 0.05). In the non-university hospitals, mean values for quality measures increased significantly over time, whereas they remained stable in the university hospital. CONCLUSIONS: Variability in performance among colonoscopists decreased significantly within the gastroenterology clinical practice. Core quality measures improved over time, mainly through improvement of the lower performers. Measurement of inter-colonoscopist variation in performance helps to identify factors that stimulate or hinder performance, and forms the basis for interventions. TRIAL REGISTRATION: http://www.trialregister.nl.

Safety and efficacy of a fully covered large-diameter self-expanding metal stent for the treatment of upper gastrointestinal perforations, anastomotic leaks, and fistula.

Upper gastrointestinal perforations, fistula, and anastomotic leaks are severe conditions with high mortality. Temporary endoscopic placement of fully covered self-expanding metal stent (fSEMS) has emerged as treatment option. Stent migration is a major drawback of currently used stents. Migration is often attributed to a relatively too small stent diameter as esophageal stents were initially intended for the treatment of strictures. This study aimed to investigate the safety and efficacy of a large-diameter fSEMS for treatment of these conditions. Data were retrospectively collected from patients who received this stent in the Netherlands between March 2011 and August 2013. Clinical success was defined as sufficient leak closure after stent removal as confirmed by endoscopy or X-ray with oral contrast without surgical intervention or placement of another type of stent. Adverse events were graded according a standardized grading system. Stent placement was performed in 34 patients for the following indications: perforation (n = 6), anastomotic leak (n = 26), and fistula (n = 2). Technical success rate was 97% (33/34). Clinical success rate was 44% (15/34) after one stent and 50% (17/34) after an additional stent. There were no severe adverse events and stent-related mortality. The overall adverse event rate was 50% (all graded 'moderate'). There were 14 (41%) stent migrations (complete n = 8, partial n = 6). Other adverse events were bleeding (n = 2) and aspiration pneumonia (n = 1). Reinterventions for failure of the large-diameter fSEMS were placement of another type of fSEMS (n = 4), surgical repair (n = 3), or esophagectomy (n = 1). Eleven patients (32%) died in-hospital because of persisting intrathoracic sepsis (n = 10) or preexistent bowel ischemia (n = 1). This study suggests that temporary placement of a large-diameter fSEMS for the treatment of upper gastrointestinal perforations, fistula, and anastomotic leaks is safe in terms of severe adverse events and stent-related mortality. The larger diameter does not seem to prevent stent migration.

Simultaneous R2*, R2, and R2' quantification by combining S0 estimation of the free induction decay with a single spin echo: A single acquisition method for R2 insensitive quantification of holmium-166-loaded microspheres.

PURPOSE: To present a new method, S0 estimation of the free induction decay combined with a single spin echo measurement (SOFIDSE), that enables simultaneous measurements of R2*, R2, and R2' in order to quantify the local concentration of holmium microspheres (Ho-MS) for radioembolization. THEORY AND METHODS: SOFIDSE estimates R2* and the signal magnitude at time point 0, S0, from a multigradient echo readout of the free induction decay and subsequently estimates R2 using S0 and a single spin echo, from which R2' is deducted. The method was evaluated by comparing SOFIDSE R2 values with values obtained from shifted spin echo (SSE) measurements on a phantom setup containing Ho-MS and from dual spin echo measurements on a healthy volunteer. RESULTS: On average, SOFIDSE showed a small overestimation of R2 values compared with SSE independent of the microsphere concentration. R2' values determined by subtraction of either SOFIDSE R2 or SSE R2 from R2* showed excellent agreement (correlation coefficient = 1; P = 9 · 10(-11)). The Ho-MS-induced R2' values obtained by SOFIDSE were insensitive to the R2 value of the tissue in which they resided. CONCLUSION: SOFIDSE enables quantification of Ho-MS, in media with spatially or temporally varying R2 values, in a single acquisition.

Metachronous colorectal cancers result from missed lesions and non-compliance with surveillance.

BACKGROUND: Several studies examined the rate of colorectal cancer (CRC) developed during colonoscopy surveillance after CRC resection (ie, metachronous CRC [mCRC]), yet the underlying etiology is unclear. OBJECTIVE: To examine the rate and likely etiology of mCRCs. DESIGN: Population-based, multicenter study. Review of clinical and histopathologic records, including data of the national pathology database and The Netherlands Cancer Registry. SETTING: National cancer databases reviewed at 3 hospitals in South-Limburg, The Netherlands. PATIENTS: Total CRC population diagnosed in South-Limburg from January 2001 to December 2010. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: We defined an mCRC as a second primary CRC, diagnosed >6 months after the primary CRC. By using a modified algorithm to ascribe likely etiology, we classified the mCRCs into cancers caused by non-compliance with surveillance recommendations, inadequate examination, incomplete resection of precursor lesions (CRC in same segment as previous advanced adenoma), missed lesions, or newly developed cancers. RESULTS: We included a total of 5157 patients with CRC, of whom 93 (1.8%) had mCRCs, which were diagnosed on an average of 81 months (range 7-356 months) after the initial CRC diagnosis. Of all mCRCs, 43.0% were attributable to non-compliance with surveillance advice, 43.0% to missed lesions, 5.4% to incompletely resected lesions, 5.4% to newly developed cancers, and 3.2% to inadequate examination. Age-adjusted and sex-adjusted logistic regression analyses showed that mCRCs were significantly smaller in size (odds ratio [OR] 0.8; 95% confidence interval [CI], 0.7-0.9) and more often poorly differentiated (OR 1.7; 95% CI, 1.0-2.8) than were solitary CRCs. LIMITATIONS: Retrospective evaluation of clinical data. CONCLUSION: In this study, 1.8% of all patients with CRC developed mCRCs, and the vast majority were attributable to missed lesions or non-compliance with surveillance advice. Our findings underscore the importance of high-quality colonoscopy to maximize the benefit of post-CRC surveillance.

Postcolonoscopy colorectal cancers are preventable: a population-based study.

OBJECTIVE: The quality of colonoscopy is key for ensuring protection against colorectal cancer (CRC). We therefore aimed to elucidate the aetiology of postcolonoscopy CRCs (PCCRCs), and especially to identify preventable factors. METHODS: We conducted a population-based study of all patients diagnosed with CRC in South-Limburg from 2001 to 2010 using colonoscopy and histopathology records and data from the Netherlands Cancer Registry. PCCRCs were defined as cancers diagnosed within 5 years after an index colonoscopy. According to location, CRCs were categorised into proximal or distal from the splenic flexure and, according to macroscopic aspect, into flat or protruded. Aetiological factors for PCCRCs were subdivided into procedure-related (missed lesions, inadequate examination/surveillance, incomplete resection) and biology-related (new cancers). RESULTS: We included a total of 5107 patients with CRC, of whom 147 (2.9% of all patients, mean age 72.8 years, 55.1% men) had PCCRCs diagnosed on average 26 months after an index colonoscopy. Logistic regression analysis, adjusted for age and gender, showed that PCCRCs were significantly more often proximally located (OR 3.92, 95% CI 2.71 to 5.69), smaller in size (OR 0.78, 95% CI 0.70 to 0.87) and more often flat (OR 1.70, 95% CI 1.18 to 2.43) than prevalent CRCs. Of the PCCRCs, 57.8% were attributed to missed lesions, 19.8% to inadequate examination/surveillance and 8.8% to incomplete resection, while 13.6% were newly developed cancers. CONCLUSIONS: In our experience, 86.4% of all PCCRCs could be explained by procedural factors, especially missed lesions. Quality improvements in performance of colonoscopy, with special attention to the detection and resection of proximally located flat precursors, have the potential to prevent PCCRCs.

A novel classification of colorectal tumors based on microsatellite instability, the CpG island methylator phenotype and chromosomal instability: implications for prognosis.

BACKGROUND: We studied the overlap between the major (epi)genomic events microsatellite instability (MSI), the CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) in colorectal cancer (CRC), and whether specific (epi)genotypes were associated with CRC-related deaths. PATIENTS AND METHODS: Molecular analyses using tumor DNA were successful in 509 CRC cases identified within the Netherlands Cohort Study in the period 1989-1993. Follow-up for the vital status until May 2005 was 100%. RESULTS: MSI (12.6%), CIMP-only (5.3%), CIMP + CIN (13.4%), CIN-only (58.2%) and triple-negative tumors (10.6%) differed significantly regarding tumor localization, differentiation grade, initial adjuvant therapy (AT) use and genetic characteristics (P ≤ 0.03). CIMP-only, CIMP + CIN and triple-negative tumors, compared with CIN-only tumors, were significantly associated with a 3.67, 2.44 and 3.78-fold risk of CRC-related deaths after 2-year follow-up (95% confidence intervals, CIs, 1.70-7.91, 1.35-4.41 and 1.97-7.25, respectively), but not after late follow-up. MSI tumors were borderline significantly associated with a 0.40-fold risk of CRC-related deaths after late follow-up (95% CI 0.15-1.03). CONCLUSION(S): This is the first study to show that specific (epi)genotypes may hold a differential prognostic value that may vary over time. Although no specific treatment data were available, an explanation for the differential findings over time might be that (epi)genotypes modify therapy response.

Center-out radial sampling with off-resonant reconstruction for efficient and accurate localization of punctate and elongated paramagnetic structures.

Accurate localization of interventional devices, for example, needles and brachytherapy seeds, is desired for interventional procedures. MRI is usually considered unsuitable for this purpose, as the induced signal voids and signal pile-ups do not necessarily represent the exact location of the devices. Center-out radial sampling with off-resonance reception (co-RASOR) has been shown to solve this problem by repositioning the signal pile-up into the geometrical center of the interventional devices. However, the multiple acquisitions required for co-RASOR resulted in a low efficiency and unsuitability for near real-time interventional purposes. Herein, we aim to increase the efficiency of co-RASOR by relying on multiple off-resonance reconstructions of a single acquisition rather than on multiple acquisitions. The soundness of this approach is shown by demonstrating the equivalence of acquisition co-RASOR and reconstruction co-RASOR, both theoretically and experimentally. An algorithm is proposed and evaluated to obtain the geometric centers of the devices, while suppressing the background. This procedure is shown to be effective, in vitro as well as ex vivo, and to yield signal intensity increases in the order of 150-400% of the average signal, in the geometric center of a brachytherapy seed and a needle, respectively. The geometric accuracy of the resultant images is confirmed by computed tomography.

Time to diagnosis in young-onset dementia as compared with late-onset dementia.

BACKGROUND: The extent to which specific factors influence diagnostic delays in dementia is unclear. Therefore, the aim of the present study was to compare duration from symptom onset to diagnosis for young-onset dementia (YOD) and late-onset dementia (LOD) and to assess the effect of age at onset, type of dementia, gender, living situation, education and family history of dementia on this duration. METHOD: Data on 235 YOD and 167 LOD patients collected from caregivers from two prospective cohort studies were used. Multiple linear regression analysis was performed. RESULTS: The duration between symptom onset and the diagnosis of YOD exceeded that of LOD by an average of 1.6 years (2.8 v. 4.4 years). Young age and being diagnosed with frontotemporal dementia were related to increases in the time to diagnosis. Subjects with vascular dementia experienced shorter time to diagnosis. CONCLUSIONS: There is a need to raise special awareness of YOD to facilitate a timely diagnosis.