High throughput surface plasmon resonance imaging method for clinical detection of presence and strength of binding of IgM, IgG and IgA antibodies against SARS-CoV-2 during CoViD-19 infection

Surface Plasmon Resonance imaging (SPRi) was used to determine the presence and strength of binding of IgG, IgM and IgA against the Receptor Binding Domain (RBD) of SARS-CoV-2 in sera of 102 CoViD-19 and non-CoViD-19 patients. The SPRi assay simultaneously measures the antibody isotype levels and the strength of binding to the RBD of ultimate 384 patient samples in one run. It turns out that during the course of the disease, the IgG levels and strength of binding increased while generally the IgM and IgA levels go down. Recovered patients all show high strength of binding of the IgG type to the RBD protein. The anti-RBD immunoglobulins SPRi assay provides additional insights in the immune status of patients recovering from CoViD-19. This new high throughput method can be applied for the assessment of the quality of the immune reaction of healthy individuals to SARS-CoV-2 and its mutants in vaccination programs.•Surface Plasmon Resonance imaging is an unprecedented technology for high throughput screening of antibody profiling of CoViD19 patients.•Fingerprinting of isotypes IgM, IgG and IgA can be performed for 384 patients in one run.•An affinity maturation effect was shown for patients recovering from CoViD19

Development of refractive errors - what can we learn from inherited retinal dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: _Study population:_ 302 patients with IRD from two ophthalmogenetic centers in the Netherlands. _Reference population:_ population-based Rotterdam Study-III and ERF Study (N=5,550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell related dystrophies were associated with the highest risk of SE high myopia 239.7; OR mild hyperopia 263.2, both P<0.0001; SE -6.86 D [SD 6.38]); followed by cone dominated dystrophies (OR high myopia 19.5, P<0.0001; OR high hyperopia 10.7, P=0.033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P<0.0001; OR high hyperopia 9.7, P=0.001; SE -2.27 D [SD 4.65]); and RPE related dystrophies (OR low myopia 2.7; P=0.001; OR high hyperopia 5.8; P=0.025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia; in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse, and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development

Dutch healthcare reform: did it result in performance improvement of health plans? A comparison of consumer experiences over time

<p>Abstract</p> <p>Background</p> <p>Many countries have introduced elements of managed competition in their healthcare system with the aim to accomplish more efficient and demand-driven health care. Simultaneously, generating and reporting of comparative healthcare information has become an important quality-improvement instrument. We examined whether the introduction of managed competition in the Dutch healthcare system along with public reporting of quality information was associated with performance improvement in health plans.</p> <p>Methods</p> <p>Experiences of consumers with their health plan were measured in four consecutive years (2005-2008) using the CQI^®health plan instrument 'Experiences with Healthcare and Health Insurer'. Data were available of 13,819 respondents (response = 45%) of 30 health plans in 2005, of 8,266 respondents (response = 39%) of 32 health plans in 2006, of 8,088 respondents (response = 34%) of 32 health plans in 2007, and of 7,183 respondents (response = 31%) of 32 health plans in 2008. We performed multilevel regression analyses with three levels: respondent, health plan and year of measurement. Per year and per quality aspect, we estimated health plan means while adjusting for consumers' age, education and self-reported health status. We tested for linear and quadratic time effects using chi-squares.</p> <p>Results</p> <p>The overall performance of health plans increased significantly from 2005 to 2008 on four quality aspects. For three other aspects, we found that the overall performance first declined and then increased from 2006 to 2008, but the performance in 2008 was not better than in 2005. The overall performance of health plans did not improve more often for quality aspects that were identified as important areas of improvement in the first year of measurement. On six out of seven aspects, the performance of health plans that scored below average in 2005 increased more than the performance of health plans that scored average and/or above average in that year.</p> <p>Conclusion</p> <p>We found mixed results concerning the effects of managed competition on the performance of health plans. To determine whether managed competition in the healthcare system leads to quality improvement in health plans, it is important to examine whether and for what reasons health plans initiate improvement efforts.</p

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking

Background: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. Methods: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020–2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Results: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 −3.2%) and 3.3% (0–16.7%) for minor and major LR, and 2.7% (0–7.0%) and 0.6% (0–4.2%) for PD and DP respectively. FTR rates were 5.4% (0–33.3%), 14.2% (0–100%), 7.5% (1.6%–28.5%) and 3.1% (0–14.9%). For major morbidity rate, corresponding rates were 9.8% (0–20.5%), 28.1% (0–47.1%), 36% (15.8%–58.3%) and 22.3% (5.2%–46.1%). For TO, corresponding rates were 73.6% (61.3%–94.4%), 54.1% (35.3–100), 46.8% (25.3%–59.4%) and 63.3% (30.7%–84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. Conclusion: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking

Assessing quality of hepato-pancreato-biliary surgery: nationwide benchmarking

Background: Clinical auditing is a powerful tool to evaluate and improve healthcare. Deviations from the expected quality of care are identified by benchmarking the results of individual hospitals using national averages. This study aimed to evaluate the use of quality indicators for benchmarking hepato-pancreato-biliary (HPB) surgery and when outlier hospitals could be identified. Methods: A population-based study used data from two nationwide Dutch HPB audits (DHBA and DPCA) from 2014 to 2021. Sample size calculations determined the threshold (in percentage points) to identify centres as statistical outliers, based on current volume requirements (annual minimum of 20 resections) on a two-year period (2020–2021), covering mortality rate, failure to rescue (FTR), major morbidity rate and textbook/ideal outcome (TO) for minor liver resection (LR), major LR, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Results: In total, 10 963 and 7365 patients who underwent liver and pancreatic resection respectively were included. Benchmark and corresponding range of mortality rates were 0.6% (0 −3.2%) and 3.3% (0–16.7%) for minor and major LR, and 2.7% (0–7.0%) and 0.6% (0–4.2%) for PD and DP respectively. FTR rates were 5.4% (0–33.3%), 14.2% (0–100%), 7.5% (1.6%–28.5%) and 3.1% (0–14.9%). For major morbidity rate, corresponding rates were 9.8% (0–20.5%), 28.1% (0–47.1%), 36% (15.8%–58.3%) and 22.3% (5.2%–46.1%). For TO, corresponding rates were 73.6% (61.3%–94.4%), 54.1% (35.3–100), 46.8% (25.3%–59.4%) and 63.3% (30.7%–84.6%). Mortality rate thresholds indicating a significant outlier were 8.6% and 15.4% for minor and major LR and 14.2% and 8.6% for PD and DP. For FTR, these thresholds were 17.9%, 31.6%, 22.9% and 15.0%. For major morbidity rate, these thresholds were 26.1%, 49.7%, 57.9% and 52.9% respectively. For TO, lower thresholds were 52.5%, 32.5%, 25.8% and 41.4% respectively. Higher hospital volumes decrease thresholds to detect outliers. Conclusion: Current event rates and minimum volume requirements per hospital are too low to detect any meaningful between hospital differences in mortality rate and FTR. Major morbidity rate and TO are better candidates to use for benchmarking

Proton and photon radiotherapy in stage III NSCLC:Effects on hematological toxicity and adjuvant immune therapy

Background and purpose: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. Materials and methods: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients. Results: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0–4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9–12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16–0.79, P = 0.01). Conclusion: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.</p

Annual outpatient hysteroscopy and endometrial sampling (OHES) in HNPCC/Lynch syndrome (LS)

Background: LS women have a 40-60 % lifetime risk of endometrial cancer (EC). Most international guidelines recommend screening. However, data on efficacy are limited. Purpose: To assess the performance of OHES for EC screening in LS and compare it with transvaginal ultrasound (TVS) alone. Methods: A prospective observational cohort study of LS women attending a tertiary high-risk familial gynaecological cancer clinic was conducted. LS women opting for EC screening underwent annual OHES and TVS. Histopathological specimens were processed using a strict protocol. Data of women screened between October 2007 and March 2010 were analysed from a bespoke database. Histology was used as the gold standard. Diagnostic accuracy of OHES was compared with TVS using specificity, and positive (PLR) and negative (NLR) likelihood ratios. Results: Forty-one LS women underwent 69 screens (41 prevalent, 28 incident). Four (three prevalent, one incident) women were detected to have EC/atypical endometrial hyperplasia (AEH), five had endometrial polyps and two had endometrial hyperplasia (EH) on OHES. TVS detected two of four EC/AEH. OHES had similar specificity of 89.8 % (CI 79.2, 96.2 %), but higher PLR 9.8 (CI 4.6, 21) and lower NLR (zero) compared to TVS: specificity 84.75 %(CI 73, 92.8 %), PLR 3.28 (CI 1.04, 10.35) and NLR 0.59 (CI 0.22, 1.58). No interval cancers occurred over a median follow-up of 22 months. The annual incidence was 3.57 % (CI 0.09, 18.35) for EC, 10.71 % (CI 2.27, 28.23) for polyps and 21.4 % (CI 8.3, 40.1) for any endometrial pathology. Conclusions: Our findings suggest that in LS, annual OHES is acceptable and has high diagnostic accuracy for EC/AEH screening. Larger international studies are needed for confirmation, given the relatively small numbers of LS women at individual centres. It reinforces the current recommendation that endometrial sampling is crucial when screening these women. © 2012 Springer-Verlag

Different patient subgroup, different ranking? Which quality indicators do patients find important when choosing a hospital for hip- or knee arthroplasty?

<p>Abstract</p> <p>Background</p> <p>Patients are increasingly expected to become active, critical consumers in healthcare. They can use comparative healthcare information presented on websites to make informed choices for healthcare providers. However, the use of this information has been limited so far. An obstacle can be that the information is not perceived as relevant by patients. Presenting only the most important quality indicators might improve the usefulness of this information. The aim of this study was to explore which quality indicators different subgroups of patients find important when choosing a hospital for total hip arthroplasty (THA) or total knee arthroplasty (TKA).</p> <p>Methods</p> <p>In this explorative, cross-sectional study, questionnaires were distributed to 265 patients who underwent or had to undergo THA/TKA. Participants were asked to rank the importance of three types of quality indicators: patient experience indicators, clinical performance indicators, and indicators about hospital services. We used random effects regression analyses to assess the relative importance of the indicators in different subgroups of patients.</p> <p>Results</p> <p>110 patients (response rate 41.5%) who underwent or had to undergo THA/TKA participated. Conduct of doctors, the presence of procedures to prevent adverse effects of thrombosis and information about the specialist area of orthopaedists were the most important patient experience indicator, clinical performance indicator and indicator about hospital services, respectively. We found a few differences between patient subgroups in the importance attached to the quality indicators.</p> <p>Conclusions</p> <p>This study provides a first insight into which quality indicators patients find important when choosing a hospital for THA/TKA, and shows that subgroups of patients differ in the value they attach to these indicators. More extended research is needed to establish the indicators that should at least be presented in succinct overviews of comparative healthcare information for patients choosing a hospital for THA/TKA.</p

How do healthcare consumers process and evaluate comparative healthcare information? A qualitative study using cognitive interviews

Background: To date, online public healthcare reports have not been effectively used by consumers. Therefore, we qualitatively examined how healthcare consumers process and evaluate comparative healthcare information on the Internet. Methods: Using semi-structured cognitive interviews, interviewees (n = 20) were asked to think aloud and answer questions, as they were prompted with three Dutch web pages providing comparative healthcare information. Results: We identified twelve themes from consumers' thoughts and evaluations. These themes were categorized under four important areas of interest: (1) a response to the design; (2) a response to the information content; (3) the use of the information, and (4) the purpose of the information. Conclusion: Several barriers to an effective use of comparative healthcare information were identified, such as too much information and the ambiguity of terms presented on websites. Particularly important for future research is the question of how comparative healthcare information can be integrated with alternative information, such as patient reviews on the Internet. Furthermore, the readability of quality of care concepts is an issue that needs further attention, both from websites and communication experts.

Understanding and using comparative healthcare information; the effect of the amount of information and consumer characteristics and skills

<p>Abstract</p> <p>Background</p> <p>Consumers are increasingly exposed to comparative healthcare information (information about the quality of different healthcare providers). Partly because of its complexity, the use of this information has been limited. The objective of this study was to examine how the amount of presented information influences the comprehension and use of comparative healthcare information when important consumer characteristics and skills are taken into account.</p> <p>Methods</p> <p>In this randomized controlled experiment, comparative information on total hip or knee surgery was used as a test case. An online survey was distributed among 800 members of the NIVEL Insurants Panel and 76 hip- or knee surgery patients. Participants were assigned to one of four subgroups, who were shown 3, 7, 11 or 15 quality aspects of three hospitals. We conducted Kruskall-Wallis tests, Chi-square tests and hierarchical multiple linear regression analyses to examine relationships between the amount of information and consumer characteristics and skills (literacy, numeracy, active choice behaviour) on one hand, and outcome measures related to effectively using information (comprehension, perceived usefulness of information, hospital choice, ease of making a choice) on the other hand.</p> <p>Results</p> <p>414 people (47%) participated. Regression analysis showed that the amount of information slightly influenced the comprehension and the perceived usefulness of comparative healthcare information. It did not affect consumers’ hospital choice and ease of making this choice. Consumer characteristics (especially age) and skills (especially literacy) were the most important factors affecting the comprehension of information and the ease of making a hospital choice. For the perceived usefulness of comparative information, active choice behaviour was the most influencing factor.</p> <p>Conclusion</p> <p>The effects of the amount of information were not unambiguous. It remains unclear what the ideal amount of quality information to be presented would be. Reducing the amount of information will probably not automatically result in more effective use of comparative healthcare information by consumers. More important, consumer characteristics and skills appeared to be more influential factors contributing to information comprehension and use. Consequently, we would suggest that more emphasis on improving consumers’ skills is needed to enhance the use of comparative healthcare information.</p