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PurposeStudies on the association between peripheral neuropathy (PN) and patient-reported outcomes have mostly overlooked sleep quality. Therefore, we aimed to assess the association between PN and sleep quality in a population-based sample of colorectal cancer (CRC) patients up two years after diagnosis. MethodsAll newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N=340) completed questionnaires about PN (EORTC QLQ-CIPN20) and sleep (PSQI) before initial treatment (baseline) and one and two years after diagnosis. ResultsPatients who developed sensory PN (n=76) or motor PN (n=79) after treatment more often reported poor sleeping scores (PSQI>5) compared with those who did not develop SPN or MPN at 1-year (SPN: 38% vs. 261%, MPN: 37% vs. 14%) and 2-year follow-up (SPN: 38 vs. 23%, MPN: 37% vs. 18%) (all pConclusionsBoth SPN and MPN were significantly associated with the course of sleep quality among CRC patients up to two years after diagnosis. Clinicians should be encouraged to discuss sleep quality with their patients who either report PN or are at risk of developing PN. Implications for survivors: Improving sleep quality among survivors with PN is important, either by reducing PN symptoms, or directly targeting sleep

Objective: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer.Summary of Background Data: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer.Methods: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods.Results: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% (P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P Conclusion: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Purpose Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio. Methods In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions. Results Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables. Conclusion We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.

Economic evaluation of early surgery compared to the endoscopy-first approach in chronic pancreatitis.In patients with painful chronic pancreatitis and a dilated main pancreatic duct, early surgery, as compared with an endoscopy-first approach, leads to more pain reduction with fewer interventions. However, it is unknown if early surgery is more cost-effective than the endoscopy-first approach.The multicenter Dutch ESCAPE trial randomized patients with chronic pancreatitis and a dilated main pancreatic duct between early surgery (surgery within 6 weeks) or the endoscopy-first approach in 30 centers (April 2011 - September 2016). Healthcare utilization was prospectively recorded up to 18 months after randomization. Unit costs of resources were determined, and cost-effectiveness and cost-utility analyses were performed from societal and healthcare perspectives. Primary outcomes were the costs per unit decrease on the Izbicki pain score and per gained quality-adjusted life-year.In total, 88 patients were included in the analysis, with 44 patients randomized to each group. Total costs were lower in the early surgery group but did not reach statistical significance (mean difference €????4,815 (95 per cent bias-corrected and accelerated confidence interval €????13,113 to €3,411; P=0.25). Early surgery had a probability percentage of 88.4% of being more cost-effective than the endoscopy-first approach at a willingness-to-pay threshold of €0 per day per unit decrease on the Izbicki pain score. The probability percentage per additional gained QALY was 75.7% at a willingness-to-pay threshold of €50,000.In patients with painful chronic pancreatitis and a dilated main pancreatic duct, early surgery was more cost-effective than the endoscopy-first approach.

BackgroundCognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.Methods204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.ResultsThree distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.ConclusionsCurrent results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Bladder cancer is mostly present in the form of urothelium carcinoma, causing over 150.000 deaths each year. Its histopathological classification as muscle invasive (MIBC) and non-muscle invasive (NMIBC) is the most prominent aspect, affecting the prognosis and progression of this disease. In this study, we defined the active regulatory landscape of MIBC and NMIBC cell lines using H3K27ac-seq and used an integrative data approach to combine our findings with existing data. Our analysis revealed FRA1 and FLI1 as the two critical transcription factors differentially regulating MIBC regulatory landscape. Importantly, we show that FRA1 and FLI1 regulate the genes involved in epithelial cell migration and cell junction organization. Knock-down of FRA1 and FLI1 in MIBC revealed the downregulation of several EMT-related genes such as MAP4K4 and FLOT1. Further, ChIP-SICAP performed for FRA1 and FLI1 enabled us to infer chromatin binding partners of these two transcription factors and link this information with their target genes, providing a comprehensive regulatory circuit for the genes implicated in invasive ability of the bladder cancer cells. Finally, for the first time we show that knock-down of FRA1 and FRA1-FLI1 double knock-down results in significant reduction of invasion capacity of MIBC cells towards muscle microenvironment using IC-CHIP assays. Our results collectively highlight the role of these two transcription factors in invasive characteristics of bladder cancer in selection and design of targeted options for treatment of MIBC.

Introduction: The Activated Clotting Time (ACT) is commonly used to manage anticoagulation during cardiac surgery. The aim of this study was to compare the older manually operated Hemochron® Response and the automated Hemochron® Signature Elite. Methods: In this observational study the clinically relevant differences of both devices were investigated simultaneously, using duplicate measurements, in 29 patients who underwent a Coronary Artery Bypass Grafting (CABG) or Aortic Valve Replacement (AVR) in order to determine reliability, bias, and to detect which method has the lowest variation. Blood samples were obtained from the arterial line prior to surgery, after administration of 300 IU/kg heparin, 5 minutes after initiation of cardiopulmonary bypass and successively every 30 minutes, and after protamine administration. Results: A total of 202 measurements were performed. Of these 10 measurements were out of range in the Response and 9 in the Elite. About 27 single unstable magnet errors were seen in the Response versus no measurement errors in the Elite. No statistically significant differences between the Response (p = 0.22, Wilcoxon rank) and Elite (p = 0.064) duplicates were observed. The Response values were consistently higher during heparinization than the Elite measurements (p = 0.002, repeated measurements) with an average positive bias of around 56 seconds during heparinization (Bland-Altman). Overall, the coefficient of variation (CoV) increased during heparinization. Conclusion: The Elite was more reliable, but the variation was higher for the Elite than the Response. The observed positive bias in the Response compared to the Elite could affect heparin administration during surgery making the two systems not interchangeable.

Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations. This study uses data from a clinical dataset—560 male subjects (266 individuals with ASD and 294 healthy individuals, CTL, mean age at 17.2 years) from the Autism Brain Imaging Data Exchange database, and data of 391 healthy individuals (207 males, mean age at 12.1 years) from the Pediatric Imaging, Neurocognition and Genetics database. ASD-related cortical alterations (group difference, ASD-CTL, in cortical thickness) and cortical correlates of polygenic risk for ASD were assessed, and then statistically compared with structural connectome-based network measures (such as hubs) using spin permutation tests. Next, we investigated whether polygenic risk for ASD could be predicted by network architecture by building machine-learning based prediction models, and whether the top predictors of the model were identified as disease epicenters of ASD. We observed that ASD-related cortical alterations as well as cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. We also observed that age progression of ASD-related cortical alterations and cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. Further investigation revealed that structural connectomes predicted polygenic risk for ASD (r = 0.30, p

OBJECTIVE: To analyze the relationship between negative lymph node (LNneg) size as a possible surrogate marker of the host antitumor immune response and overall survival (OS) in esophageal cancer (EC) patients.BACKGROUND: Lymph node (LN) status is a well-established prognostic factor in EC patients. An increased number of LNnegs is related to better survival in EC. Follicular hyperplasia in LNneg is associated with better survival in cancer-bearing mice and might explain increased LN size.METHODS: The long axis of 304 LNnegs was measured in hematoxylin-eosin stained sections from resection specimens of 367 OE02 trial patients (188 treated with surgery alone (S), 179 with neoadjuvant chemotherapy plus surgery (C+S)) as a surrogate of LN size. The relationship between LNneg size, LNneg microarchitecture, clinicopathological variables, and OS was analyzed.RESULTS: Large LNneg size was related to lower pN category (P = 0.01) and lower frequency of lymphatic invasion (P = 0.02) in S patients only. Irrespective of treatment, (y)pN0 patients with large LNneg had the best OS. (y)pN1 patients had the poorest OS irrespective of LNneg size (P < 0.001). Large LNneg contained less lymphocytes (P = 0.02) and had a higher germinal centers/lymphocyte ratio (P = 0.05).CONCLUSIONS: This is the first study to investigate LNneg size in EC patients randomized to neoadjuvant chemotherapy followed by surgery or surgery alone. Our pilot study suggests that LNneg size is a surrogate marker of the host antitumor immune response and a potentially clinically useful new prognostic biomarker for (y)pN0 EC patients. Future studies need to confirm our results and explore underlying biological mechanisms.

Objective: To assess facial esthetics and quality of life (QoL) as measure of success or failure after maxillomandibular advancement (MMA) surgery for obstructive sleep apnea (OSA). Methods: Visual analog scales (VAS) on facial esthetics and QoL survey, including EQ-5D3L, Epworth Sleepiness Scale (ESS), and Functional Outcome of Sleep Questionnaire (FOSQ) were collected. Outcomes were analyzed for surgical-success/failure after MMA. Results: Forty-one patients returned completed surveys (response: 66%). Mean VAS on facial esthetics was 57 ± 22 mm preoperative and 51 ± 24 mm postoperative (p = 0.217). When MMA was considered a surgical-failure, VAS was significantly more negative (40 ± 22 mm; p = 0.026). EQ-5D-3L showed an overall mean score of 73.2 ± 15.7, ESS was 6.3 ± 5.4, and FOSQ was 16.0 ± 3.3. Conclusion: No significant alteration of facial esthetics were reported after MMA; however, lower QoL was associated with surgical-failure; whereas, in surgical-success, QoL were higher.

In the above published article there was an editing error in Table 1. The corrected table is shown below. The publishers apologise for this error.

Background Digital interventions for anxiety disorders are a promising solution to address barriers to evidence-based treatment access. Precise and powerful estimates of digital intervention effectiveness for anxiety disorders are necessary for further adoption in practice. The present systematic review and meta-analysis examined the effectiveness of digital interventions across all anxiety disorders and specific to each disorder v. wait-list and care-as-usual controls. Methods A systematic search of bibliographic databases identified 15 030 abstracts from inception to 1 January 2020. Forty-seven randomized controlled trials (53 comparisons; 4958 participants) contributed to the meta-analysis. Subgroup analyses were conducted by an anxiety disorder, risk of bias, treatment support, recruitment, location and treatment adherence. Results A large, pooled effect size of g = 0.80 [95% Confidence Interval: 0.68–0.93] was found in favor of digital interventions. Moderate to large pooled effect sizes favoring digital interventions were found for generalized anxiety disorder (g = 0.62), mixed anxiety samples (g = 0.68), panic disorder with or without agoraphobia (g = 1.08) and social anxiety disorder (g = 0.76) subgroups. No subgroups were significantly different or related to the pooled effect size. Notably, the effects of guided interventions (g = 0.84) and unguided interventions (g = 0.64) were not significantly different. Supplemental analysis comparing digital and face-to-face interventions (9 comparisons; 683 participants) found no significant difference in effect [g = 0.14 favoring digital interventions; Confidence Interval: −0.01 to 0.30]. Conclusion The precise and powerful estimates found further justify the application of digital interventions for anxiety disorders in place of wait-list or usual care.

BackgroundTraditional genotype-phenotype correlations for the succinate dehydrogenase-complex II (SDH) genes linkSDHBvariants to thoracic-abdominal pheochromocytoma-paraganglioma (PPGL) andSDHDvariants to head and neck paraganglioma (HNPGL). However, in a recent study we found strong and specific genotype-phenotype associations forSDHDvariants. In the present study we zoom in on the genotype-phenotype associations ofSDHBgene variants, considering the impact of individual gene variants on disease risk and risk of malignancy.MethodsWe analysed two large independent data sets, including a total of 448 patients with PPGL and HNPGL, and studied the association of missense or truncatingSDHBvariants with tumour incidence, age of onset and malignancy risk using binomial testing and Kaplan-Meier analysis.ResultsCompared with missense variants, truncatingSDHBvariants were significantly and consistently more common in patients with PPGL, by a 20 percentage point margin. Malignancy was also significantly more common in truncating versus missense variant carriers. No overall differences in age of PPGL onset were noted between carriers of the two variant types, although some individual variants may differ in certain cases. Missense variants were marginally over-represented among patients with HNPGL, but the difference was not statistically significant.ConclusionSDHBtruncating variants convey an elevated risk for development of both PPGL and malignancy compared with missense variants. These results further support earlier robust associations between truncating variants and PPGL, and also suggest that the two variant types differ in their impact on complex II function, with PPGL/HNPGL tissues displaying differing sensitivities to changes in complex II function.

BACKGROUND: Colon cancer affects a patient's ability to work. Many patients who have colon cancer are employed at the time of diagnosis.OBJECTIVE: We evaluated work ability during the first 2 years after colon cancer diagnosis.DESIGN: This study is a national prospective study, the Prospective Dutch ColoRectal Cancer cohort, including clinical data and patient-reported outcomes.SETTINGS: Data were collected in 59 medical centers in the Netherlands.PATIENTS: Patients MAIN OUTCOME MEASURES: Work ability was assessed at baseline, 3, 6, 12, 18, and 24 months. The Work Ability Index (range, 0 to 49) was evaluated using linear mixed models. Outcomes were matched to population controls without cancer.RESULTS: Of 390 patients, 84% had paid employment. Work ability of patients with stage I to IV colon cancer was significantly lower at the time of diagnosis than in matched population controls (31 ± 8.2 and 41 ± 5.6). Patients with stage I to III disease receiving surgery only regained Work Ability Index scores comparable to matched population controls at 18 months. Patients receiving adjuvant systemic treatment initially demonstrated a decrease in work ability with improvements from 6 months onward and normalization at 24 months. Patients with stage IV disease did not demonstrate improvements in work ability outcomes over time. Work ability scores were negatively influenced by the administration of systemic treatment and ≥1 comorbidities.LIMITATIONS: Only patients with patient-reported outcomes and work at baseline were included in this analysis. Also, questionnaire response rates decreased over time.CONCLUSIONS: Work ability in patients with colon cancer is decreased for a prolonged time. Recovery depends on disease stage, type of treatment, and comorbidities. Patients with stage I to III disease treated with curative surgery alone were the first to regain work ability, followed by patients who receive adjuvant chemotherapy. Patients with stage IV disease did not regain work ability. See Video Abstract at http://links.lww.com/DCR/B759 .CAPACIDAD LABORAL EN PACIENTES CON CNCER DE COLON EN ESTADIO IIV RESULTADOS PROSPECTIVOS DE CNCER COLORECTAL EN UNA COHORTE HOLANDESA: ANTECEDENTES:El cáncer de colon afecta la capacidad de trabajo en un paciente. Muchos pacientes con cáncer de colon están empleados en el momento del diagnóstico.OBJETIVO:Evaluamos la capacidad laboral durante los dos primeros años posteriores al diagnóstico de cáncer de colon.DISEÑO:Es un estudio prospectivo nacional, la cohorte de cáncer colorrectal holandés, incluye datos clínicos y resultados informados por los pacientes.ENTORNO CLINICO:Se recopilaron datos de 59 centros médicos en los Países Bajos.PACIENTES:Se seleccionaron pacientes < 67 años, con cáncer de colon en estadio I-IV, que completaron los cuestionarios de índice de capacidad para el trabajo.PRINCIPALES MEDIDAS DE VALORACIÓN:La capacidad para el trabajo se evaluó al inicio, a los 3, 6, 12, 18 y 24 meses. El índice de capacidad para el trabajo (que va de 0 a 49) se evaluó mediante modelos lineales mixtos. Los resultados fueron comparados con el grupo control sin cáncer.RESULTADOS:De 390 pacientes, el 84% tenía un empleo remunerado. La capacidad de trabajo de los pacientes en estadio I-IV fue significativamente menor en el momento del diagnóstico en comparación con el grupo control (31 ± 8,2 y 41 ± 5,6, respectivamente). Los pacientes con enfermedad en estadio I-III que recibieron cirugía lograron recuperar puntajes del índice de capacidad laboral comparables a los controles a los 18 meses. Los pacientes que recibieron tratamiento sistémico adyuvante inicialmente demostraron una disminución en la capacidad de trabajo con mejoras a partir de los 6 meses en adelante y una normalización a los 24 meses. Los pacientes en estadio IV no demostraron mejoras en los resultados de la capacidad laboral a lo largo del tiempo. Las puntuaciones de capacidad para el trabajo se vieron influidas negativamente por la administración del tratamiento sistémico y la existencia de ≥1 comorbilidades.LIMITACIONES:En este análisis solo se incluyeron los pacientes con resultados y trabajo desde el inicio del estudio. Además, las tasas de respuesta al cuestionario disminuyeron con el tiempo.CONCLUSIONES:La capacidad de trabajo en pacientes con cáncer de colon se reduce durante un tiempo prolongado. La recuperación depende del estadio de la enfermedad, el tipo de tratamiento y la comorbilidad. Los pacientes con enfermedad en estadio I-III tratados con cirugía curativa exclusivamente, son los primeros en recuperar la capacidad para trabajar, seguidos de los pacientes que reciben quimioterapia adyuvante. Los pacientes con enfermedad en estadio IV no recuperan la capacidad para trabajar. Consulte Video Resumen en http://links.lww.com/DCR/B759 . (Traducción- Dr. Ingrid Melo ).

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

OBJECTIVE: Since Wnt signaling plays an important role in both tooth agenesis and altered intestine homeostasis, the aim was to compare gastrointestinal symptoms in patients with isolated oligodontia caused by a Wnt pathway gene mutation and controls.METHODS: A case-control study was designed to compare self-reported gastrointestinal symptoms among patients with isolated oligodontia, caused by a Wnt signaling gene mutation, and fully dentate controls. The Gastrointestinal Symptom Rating Scale (GSRS) was used to assess gastrointestinal symptoms. Prevalence and severity of gastrointestinal symptoms among patients and age- and gender-matched controls was evaluated.RESULTS: Twenty patients with isolated oligodontia and a pathogenic variant in the wnt pathway genes WNT10A, LRP6 or PAX9 participated. The prevalence of gastrointestinal symptoms was higher in the oligodontia patients compared to their controls (Χ2 (1) = 87.33, p = .008). Mean GSRS total scores (p = .011) and domain scores for 'abdominal pain' (p = .022), 'reflux' (p = .003) and constipation (p = .030) were higher for these oligodontia patients compared to their controls.CONCLUSION: Gastrointestinal symptoms are more prevalent and more severe in patients with isolated oligodontia and a deficiency in a Wnt pathway related gene, when compared to controls without tooth agenesis.

BACKGROUND: A watch & wait strategy for patients with rectal cancer with a clinical complete response after neoadjuvant chemoradiotherapy is a valuable alternative for rectal resection. However, there are patients who will have residual tumor or regrowth during watch & wait.OBJECTIVE: The aim was to investigate safety and costs for patients who underwent delayed surgery after neoadjuvant chemoradiotherapy.DESIGN: This is a retrospective cohort study with prospectively collected data.SETTINGS: The study was conducted at a large teaching hospital.PATIENTS: Between Jan 2015 - May 2020, 622 new rectal cancer patients were seen of which 200 received neoadjuvant chemoradiotherapy. Ninety-four patients were included of which 65 patients underwent immediate surgery and 29 patients required delayed surgery after an initial watch & wait approach.MAIN OUTCOME MEASURES: This included 30-day postoperative morbidity rate, hospital costs and two-year overall and disease-free survival.RESULTS: There was no difference in length of stay (9 vs 8, p = 0.83), readmissions (27.6% vs 10.0%, p = 0.10), surgical re-interventions (15.0% vs 3.4%, p = 0.16) and stoma free rate (52.6% vs 31.0%, p = 0.09) between immediate and delayed surgery groups. Hospital costs were similar in the delayed group (€11913 vs €13769, p = 0.89). Two-year overall survival (93% vs 100%, p = 0.23) and disease-free survival (78% vs 81%, p = 0.47) rates were comparable.LIMITATIONS: Small sample size, follow-up time and retrospective design.CONCLUSION: Delayed surgery for regrowth in a watch & wait program or for persistent residual disease after a repeated assessment is not associated with an increased risk of postoperative morbidity or a significant rise in costs compared to immediate total mesorectal excision. There also appears to be no evident compromise in oncological outcome. Repeated response assessment in patients with a near complete clinical response after neoadjuvant chemoradiotherapy is a useful approach to identify more patients who can benefit from a watch & wait strategy. See Video Abstract at http://links.lww.com/DCR/B836 .

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems., European Child & Adolescent Psychiatry, 32 (8), ISSN:1435-165X, ISSN:1018-8827

Introduction: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. Methods: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Results: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p = 0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Conclusion: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.

Hypoxic insults initiate a cascade of biochemical events that result in irreversible neuronal damage. Magnesium sulfate agent has a possible neuroprotective effect as it can work at different stages of hypoxic brain injury. Objectives: Magnesium sulfate is used in the neonatal management of HIE as an adjunct medication to reduce Hypoxic Neuronal injury. In this Vitro study, we aimed to examine the efficacy of using magnesium sulfate in human cells to reduce oxygen consumption. We used in-vitro method utilizing foreskin as human cell surrogate. Method: Foreskin specimens from healthy newborns were collected immediately after circumcision and processed within 1 h for measuring the cellular rate of O2 consumption. Samples were placed in the oxygen phosphorescence analyzer and allowed to run for approximately 1 h. Injection then added magnesium sulfate at different doses into the vial. We analyze the O2 consumption in the samples at different levels of Magnesium Sulfate; the results were plotted using Kaleida Graph TM software. Results: The rate of respiration reduced with increasing the dose of MgSo4. The Cumulative analysis of cellular respiration rate was before and after an addition of MgSO4 . Collectively yielding a (k) value of 0.08 μM O2 /min µM O2 min-1 mg- and 0.04 M O2 /min µM O2 min-1 mg- respectively with a significant P-value of

Background Protection against Plasmodium falciparum is observed in a population deficient in glucose-6-phosphate dehydrogenase (G6PD), particularly in African and Mediterranean regions. However, such protection remains unknown among G6PD-deficient individuals in Southeast Asia. Methods In this study, we assessed the invasion and maturation of P falciparum K1 in a culture of erythrocytes isolated from Thai subjects carrying Viangchan (871G > A) and Mahidol (487G > A). Results We found that the parasites lost their ability to invade hemizygous and homozygous G6PD-deficient erythrocytes of Viangchan and Mahidol variants in the second and third cycles of intraerythrocytic development. It is interesting to note that P falciparum parasites selectively grew in erythrocytes from hemi- and homozygous genotypes with normal G6PD activity. Moreover, externalization of phosphatidylserine upon P falciparum infection was significantly increased only in Viangchan hemizygous variant cells. Conclusions This study is the first to show that blockage of invasion in long-term culture and potentially enhanced removal of parasitized erythrocytes were observed for the first time in erythrocytes from Viangchan and Mahidol G6PD-deficient individuals.

This research opinion paper advocates for a new system of treating viral infections and diseases, it lays more emphasis on the current virus called Covid -19 virus (Corona Virus), it is a new innovation different from the known methods of treating viral infections and diseases. Some of the known methods include use of vaccines, anti -viral medication, monoclonal, serology. Most recently, stem cells have proved to be very effective in solving complex medical diseases such as leukemia, cancer and a host of other medical diseases that pose difficult challenges to the medical field. This method could be used to cure covid-19 permanently and then simulated to solve and cure other viral infections such as HIV and AIDS, Ebola, Hanta Virus and a host of other diseases like Malaria, Chicken-Pox, Small Pox, Measles etc. It is worthy to note that viruses are always evolving by way of mutation and are developing intelligent and strategic ways to beat or avoid being detected by the immune system, this can be seen in HIV and AIDS virus which attacks CD4 cells and even goes as far as engaging and fighting to wear down the T-Cells. Also, Covid -19 tries to proofread the cells to counter anti-viral drugs such as Ribavirin. Although Remdesivir anti-viral medication which has proven to work on some covid-19 patients, cannot be proofread by the corona virus. More insight about this "Autologous stem cells trapping mechanism" is discussed under conceptual framework of this research paper and attention should also be given to the suggestions and recommendations as they hold potential methods to permanently stop the actions of viruses in invading the human cells.

Introduction In the current scenario, in which evidence-based medicine is almost obligatory, therapeutic approaches are increasingly being restricted to measures that are proven to bring benefits to the patient. Transfusion therapy follows the same concept. Even though it can be an essential support procedure in some situations, it must be carefully used, exclusively in situations in which the literature assures scientific support for its usage. Transfusion exposes patients to risks and complications, so it is necessary that we, as doctors, continue working to reduce possible mistakes involving the practice of this type of therapy. Objective To analyze if the red blood cell requests are properly made, analyzing the indication written on them (by the doctor, comparing them to the references in the actual literature. Method In this research, we have analyzed and reviewed the requests for red blood cell concentrates between August and September of 2018 received at the Hematology and Hemotherapy Center studied to find the most common mistakes made by requesters/doctors. Results A total of 397 of the 754 analyzed requests were evaluated as inadequate. Therefore, 1 out of every 2 transfusions performed did not have their requests properly completed in the city of Cascavel, Parana. Conclusions The number of inappropriate requests was high during the studied period, especially when compared to studies available in the literature. The number of inadequacies suggests that the blood component requests and the subsequent evaluation by the transfusion agency needs to be better addressed in clinical practice.

Background Early-life severe respiratory syncytial virus (RSV) infection has been associated with subsequent risk of asthma and recurrent wheeze. However, changes in the association over time and the interaction effect of the age at first RSV infection are less well understood. We aimed to assess the time-varying association between RSV and subsequent asthma and wheeze admission and explore how the association was affected by the age at RSV infection. Methods We retrospectively followed up a cohort of 23 365 children for a median of 6.9 years using Scottish health databases. Children who were born between 2001 and 2013 and had RSV-associated respiratory tract infection (RTI) admissions under 2 years were in the exposed group; those with unintentional accident admissions under 2 years comprised the control group. The Cox proportional-hazards model was used to report adjusted hazard ratios (HRs) of RSV admissions on subsequent asthma and wheeze admissions. We did subgroup analyses by follow-up years. We also explored how this association was affected by the age at first RSV admission. Results The association was strongest in the first 2 years of follow-up and decreased over time. The association persisted for 6 years in children whose first RSV-RTI admission occurred at 6–23 months of age, with an adjusted HR of 3.9 (95% confidence interval [CI], 3.1–4.9) for the first 2 years, 2.3 (95% CI, 1.6–3.2) for 2 to Conclusions We found a more persistent association for subsequent asthma and wheeze in children whose first severe RSV infection occurred at 6–23 months compared to those whose first severe RSV infection occurred at 0–6 months. This provides new evidence for further assessment of the association and RSV intervention programs.

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease. Age-related processes such as senescence, inflammaging, autophagy and mitochondrial dysfunction are interconnected biological processes that diminish the regenerative capacity of the aged heart and lung and have been shown to play a crucial role in cardiac fibrosis and idiopathic pulmonary fibrosis. This review focuses on these four processes of aging in relation to their role in fibrosis. It has long been established that the heart and lung are linked both functionally and anatomically when it comes to health and disease, with an ever-expanding aging population, the incidence of fibrotic disease and therefore the number of fibrosis-related deaths will continue to rise. There are currently no feasible therapies to treat the effects of chronic fibrosis therefore highlighting the importance of exploring the processes of aging and its role in inducing and exacerbating fibrosis of each organ. The focus of this review may help to highlight potential avenues of therapeutic exploration.

Background Studies show that prenatal maternal anxiety may act as a risk factor for adverse birth outcomes, whilst prenatal social support may rather act as a protective factor. However, studies examining prenatal anxiety symptoms, prenatal perceived support, and neonatal and/or obstetric outcomes are lacking. Objective This study investigated whether, in a community sample, prenatal perceived support: (1) had a protective influence on birth outcomes (gestational age (GA), birthweight (BW), 5-minute Apgar score, and mode of delivery); (2) acted as a protective factor, moderating the relationship between anxiety symptoms and the aforementioned birth outcomes. Method During their third trimester of pregnancy, 182 nulliparous child-bearers completed standardized questionnaires of anxiety (HADS-A) and perceived support (MOS-SSS). Birth outcomes data was extracted from medical records. Results (1) Perceived support did not significantly predict any birth outcomes. However, perceived tangible support - MOS-SSS subscale assessing perceived material/financial aid - significantly positively predicted the 5-minute Apgar score. (2) Perceived support did not significantly moderate the relationship between anxiety symptoms and birth outcomes. However, perceived tangible support significantly moderated the relationship between anxiety symptoms and the 5-minute Apgar score. Conclusion When experienced within non-clinical thresholds, prenatal anxiety symptoms do not increase the risk of adverse neonatal and obstetric outcomes when perceived support is present.

Background Chest radiography (CR) patterns for the diagnosis of COVID-19 have been established. However, they were not ideated comparing CR features with those of other pulmonary diseases. Purpose To create the most accurate COVID-19 pneumonia pattern comparing CR findings of COVID-19 and non-COVID-19 pulmonary diseases and to test the model against the British Society of Thoracic Imaging (BSTI) criteria. Material and Methods CR of COVID-19 and non-COVID-19 pulmonary diseases, admitted to the emergency department, were evaluated. Assessed features were interstitial opacities, ground glass opacities, and/or consolidations and the predominant lung alteration. We also assessed uni-/bilaterality, location (upper/middle/lower), and distribution (peripheral/perihilar), as well as pleural effusion and perihilar vessels blurring. A binary logistic regression was adopted to obtain the most accurate CR COVID-19 pattern, and sensitivity and specificity were computed. The newly defined pattern was compared to BSTI criteria. Results CR of 274 patients were evaluated (146 COVID-19, 128 non-COVID-19). The most accurate COVID-19 pneumonia pattern consisted of four features: bilateral alterations (Expß=2.8, P=0.002), peripheral distribution of the predominant (Expß=2.3, P=0.013), no pleural effusion (Expß=0.4, P=0.009), and perihilar vessels’ contour not blurred (Expß=0.3, P=0.002). The pattern showed 49% sensitivity, 81% specificity, and 64% accuracy, while BSTI criteria showed 51%, 77%, and 63%, respectively. Conclusion Bilaterality, peripheral distribution of the predominant lung alteration, no pleural effusion, and perihilar vessels contour not blurred determine the most accurate COVID-19 pneumonia pattern. Lower field involvement, proposed by BSTI criteria, was not a distinctive finding. The BSTI criteria has lower specificity.

Objective: The study objective was to analyze temporal changes in baseline and procedural characteristics and long-term survival of patients undergoing surgical aortic valve replacement over a 30-year period. Methods: A retrospective analysis of patients undergoing surgical aortic valve replacement between 1987 and 2016 in the Erasmus Medical Center (Rotterdam, The Netherlands) was conducted. Patient baseline and procedural characteristics were analyzed in periods according to the date of surgical aortic valve replacement (period A: 1987-1996; B: 1997-2006; C: 2007-2016). Survival status was determined using the Dutch National Death Registry. Relative survival was obtained by comparing the survival after surgical aortic valve replacement with the survival of the age-, sex-, and year-matched general population. Results: Between 1987 and 2016, 4404 patients underwent SAVR. From period A to C, the mean age increased from 63.9 ± 11.2 years to 66.2 ± 12.3 years (P < .001), and the prevalence of diabetes mellitus, hypertension, hypercholesterolemia, previous myocardial infarction, and previous stroke at baseline increased (P values for trend for all < .001). The prevalence of concomitant procedures increased from 42.4% in period A to 48.3% in period C (P = .004). Bioprosthesis use increased significantly (18.8% in period A vs 67.1% in period C, P < .001). Mean survival after surgical aortic valve replacement was 13.8 years. Relative survival at 20 years in the overall cohort was 60.4% (95% confidence interval, 55.9-65.2) and 73.8% (95% confidence interval, 67.1-81.1) in patients undergoing isolated primary surgical aortic valve replacement. Conclusions: Patient complexity has been continuously increasing over the last 30 years, yet long-term survival after surgical aortic valve replacement remains high compared with the age-, sex-, and year-matched general population.

Purpose Osteosynthetic treatment strategies of PHFs include MIPO or ORIF techniques. The aim of this study was to compare the 1 year outcome following either technique in type B PHFs. Methods This study was designed as a retrospective cohort study of patients treated at one academic Level 1 trauma center. Patients from 2009 to 2019 who required surgical treatment of a type B PHF were eligible to be included in this study. Patients with A- or C-type fractures or patients requiring arthroplasty were excluded. All patients were treated with Proximal Humerus Interlocking System (PHILOS) and stratified according the approach into Group MIPO or Group ORIF. Outcome measures include local complications that occurred during hospitalization, nonunion after 12 months, and range of motion after 1 year follow-up. Results This study included 149 (75.3%) patients in Group ORIF, and 49 (24.7%) in Group MIPO. The fracture morphology and concomitant injuries were comparable amongst these groups. When compared with Group MIPO, Group ORIF had a 2.6 (95% CI 0.6–11.7) higher risk of suffering from local complications. The rate of postoperative nerve lesions was comparable (OR 0.9, 95% CI 0.1–9.7) as was the rate of soft tissue complications (OR 2.0, 95% CI 0.2–17.2). The risk for nonunion was 4.5 times higher (95% 1.1–19.5) in Group ORIF when compared with Group MIPO. Group MIPO had a higher chance of flexion above 90° (OR 8.2, 95% CI 2.5–27.7). Conclusion This study provides indications that patients following surgical treatment of PHFs in MIPO technique might have favourable outcome. Large-scale and high-quality studies are warranted to confirm these results.

Objective: : To develop an international Core Outcome Set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children.Summary Background Data: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS.Methods: The development process consisted of four phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a two-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS.Results: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (eight countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with ten outcomes emerging with consensus. After two young peoples’ focus groups, two additional outcomes were added to the final COS (12): mortality, bowel obstruction, intra-abdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications.Conclusion: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment of simple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

Background/aimsFuchs’ uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS.MethodsThe clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020. A total of 593 patients with FUS and 625 patients with non-FUS from northern China were enrolled for the development of diagnostic criteria for FUS. Three hundred and seventy-seven patients with FUS and 503 patients with non-FUS from southern China were used to validate the criteria. Clinical symptoms and ocular signs were collected from all patients with FUS and patients with non-FUS. Multivariate two-step cluster analysis, logistic regression and decision tree algorithms in combination with the clinical judgement of uveitis experts were used to revise diagnostic criteria for FUS.ResultsThree essential findings including diffuse iris depigmentation, absence of posterior synechiae, mild inflammation in the anterior chamber at presentation and five associated findings including mostly unilateral involvement, cataract, vitreous opacities, absence of acute symptoms and characteristic iris nodules were used in the development of FUS diagnostic criteria. All essential findings were required for the diagnosis of FUS, and the diagnosis was further strengthened by the presence of associated findings.ConclusionRevised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).

BACKGROUND: Historically, impaired glucose metabolism has been associated with early and late complicated clinical outcomes after cardiac surgery; however, such a condition is not specific to subjects with diabetes mellitus and involves a larger patient population.METHODS: Databases were screened (January 2000 to December 2020) to identify eligible articles; studies that evaluated the association between preoperative metabolic status, as assessed by glycosylated hemoglobin levels and clinical outcomes, were considered. The studies were stratified in thresholds by baseline glycosylated hemoglobin level (lower vs higher).RESULTS: Thirty studies, involving 34,650 patients, were included in the review. In a meta-analysis stratified by glycosylated hemoglobin levels, early mortality was numerically reduced in each threshold comparison and yielded the highest reductions when less than 5.5% versus greater than 5.5% glycosylated hemoglobin levels were compared (risk ratio, 0.39; 95% confidence interval, 0.18-0.84; P = .02). Comparing higher glycosylated hemoglobin threshold values yielded comparable results. Late mortality was reduced with lower levels of glycosylated hemoglobin. Low preoperative glycosylated hemoglobin was associated with the lowest risk of sternal wound infections (risk ratio, 0.50; 95% confidence interval, 0.32-0.80; P = .003 and risk ratio, 0.53; 95% confidence interval, 0.39-0.70; P < .0001) for comparisons of less than 7.5% versus greater than 7.5% and less than 7.0% versus greater than 7.0% glycosylated hemoglobin thresholds, respectively. Additionally, levels of glycosylated hemoglobin lower than 7% were associated with reduced hospital stay, lower risk of stroke/transient ischemic attack (risk ratio 0.53; 95% confidence interval, 0.39-0.70; P < .0001), and acute kidney injury (risk ratio, 0.65; 95% confidence interval, 0.54-0.79; P < .0001).CONCLUSIONS: Lower levels of glycosylated hemoglobin in patients undergoing cardiac surgery are associated with a lower risk of early and late mortality, as well as in the incidence of postoperative acute kidney injury, neurologic complications, and wound infection, compared with higher levels.

Background National strategies from North America call for substantive improvements in entry-level pain management education to help reduce the burden of chronic pain. Past work has generated a valuable set of interprofessional pain management competencies to guide the education of future health professionals. However, there has been very limited work that has explored the development of such competencies for individual professions in different regions. Developing profession-specific competencies tailored to the local context is a necessary first step to integrate them within local regulatory systems. Our group is working toward this goal within the context of entry-level physiotherapy (PT) programs across Canada. Aims This study aimed to create a consensus-based competency profile for pain management, specific to the Canadian PT context. Methods A modified Delphi design was used to achieve consensus across Canadian university-based and clinical pain educators. Results Representatives from 14 entry-level PT programs (93% of Canadian programs) and six clinical educators were recruited. After two rounds, a total of 15 competencies reached the predetermined endorsement threshold (75%). Most participants (85%) reported being “very satisfied” with the process. Conclusions This process achieved consensus on a novel pain management competency profile specific to the Canadian PT context. The resulting profile delineates the necessary abilities required by physiotherapists to manage pain upon entry to practice. Participants were very satisfied with the process. This study also contributes to the emerging literature on integrated research in pain management by profiling research methodology that can be used to inform related work in other health professions and regions.

Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P

Item does not contain fulltext To evaluate pectus excavatum, 3-dimensional surface imaging is a promising radiation-free alternative to computed tomography and plain radiographs. Given that 3-dimensional images concern the external surface, the conventional Haller index, and correction index are not applicable as these are based on internal diameters. Therefore, external equivalents have been introduced for 3-dimensional images. However, cut-off values to help determine surgical candidacy using external indices are lacking. A prospective cohort study was conducted. Consecutive patients referred for suspected pectus excavatum received a computed tomography (≥18 years) or plain radiographs (

Aim:This study aims to compare the gating signals of patients with lung cancer recorded during the planning computed tomography scan with the ones recorded during treatment fractions. The results provide insights into how representative the respiratory signals from the planning scan are for radiation dose partitioning.Materials and methods:The amplitude and frequency of the respiratory signals of 29 patients with lung carcinoma were analysed and compared with the amplitude and frequency of those recorded during their planning scans. Moreover, a cross-correlation analysis was performed between the difference between the planning scan and fractions and features from the planning scan.Results:Two patients showed significantly different amplitude and frequency during treatment fractions compared to those from the planning scan. These patients showed low variances in frequency and amplitude during the different fractions. The difference between planning scan and fractions is correlated with the variances within the planning scan.Findings:Respiratory signals can differ between the planning scan and the fractions. In this case, a new planning scan may be beneficial. The respiratory signals from the planning scan may be predictive of whether the planning scan will be representative and usable as a control measure during radiotherapy fractions.

Aims Although soluble interleukin 2 receptor (sIL‐2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL‐2R was associated with clinical outcomes and to clarify the relationship between sIL‐2R levels and disease activity in patients with CS. Methods and results We examined 83 consecutive patients with CS in our hospital who had available serum sIL‐2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all‐cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18F‐fluorideoxyglucose positron emission tomography/computed tomography. During a median follow‐up period of 2.96 (IQR 2.24–4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL‐2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL‐2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63–8.44, P = 0.002), even after adjustment for significant covariates. sIL‐2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27). Conclusions Increased sIL‐2R is associated with worse long‐term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.

BackgroundEvidence is lacking to what extent patients with Whiplash-Associated Disorders (WAD), those with non-traumatic neck pain (NTNP), and pain-free individuals differ regarding type and severity of impairments, disability, and psychological factors.Objective To compare clinical characteristics between patients with WAD, with NTNP, and pain-free individuals in primary care physiotherapy. Additionally, differences between patient groups for both acute and chronic symptoms were assessed.MethodA cross-sectional study was conducted including 168 patients with WAD, 336 matched patients with NTNP, and 336 pain-free individuals. Differences and prevalence rates were calculated for pain intensity, pain distribution, cervical range of motion, neck flexor muscle endurance, self-reported disability, and psychological factors.Results Patients with WAD had higher pain intensity (median 6/10 vs. 5/10 p83%) scored in the normal range. No significant differences between the patient groups were observed (p>.16). Both patient groups scored significantly worse than pain-free individuals on all characteristics. Patients with WAD and NTNP experienced different types of activity limitations and participation restrictions.ConclusionWAD is a more severe condition than NTNP and should be considered a separate subgroup. A different approach in clinical practice and research is required for WAD and NTNP.

Purpose To identify possible technological solutions that can contribute to stroke patients' participation at home. Methods In this qualitative case study, data on factors that negatively influenced participation at home were collected via semi-structured interviews with stroke patients (n = 6). Additionally, data on possible technologies to improve this participation were collected via a group interview with experts (n = 4). The domains "cognition, mobility, self-care, and getting along" (International Classification of Functioning, Disability and Health) guided the data collection and interpretation; open, axial and selective coding was part of the analysis. Results Patients reported 21 factors negatively influencing participation at home, including psychological, cognitive, and physical factors. Experts suggested technological solutions regarding these factors to increase participation of stroke patients; digital assistants, apps, and virtual reality were frequently mentioned. To facilitate the use of these technologies, experts indicated the importance of involving patients in their design. They also suggested that rehabilitation specialists and family members could support the uptake and use of technologies. Conclusions Various technologies were identified by experts as having the potential to improve the participation of stroke patients in their homes. Future research may study the influence of these technologies on the actual participation of stroke patients at home.Implications for rehabilitationThe identified technological solutions can support rehabilitation specialists in guiding stroke patients towards technologies that can support a patient's participation at home.Rehabilitation specialists can be champions in introducing, recommending and promoting technologies to stroke patients and their families, as well as in training them to use technologies.Virtual reality as a technology can be part of rehabilitation, not only to train stroke patients in daily life activities but also to increase empathy and understanding in caregivers and carers on stroke impairments.Rehabilitation specialists can recommend technologies integrated in daily life and presented as general consumer goods; stroke patients are more likely to adopt these kind of technologies.

Background Interstitial lung disease (ILD) patients often develop lung cancer. However, previous studies on the incidences of lung cancer in ILD patients focused on specific aetiologies, such as idiopathic pulmonary fibrosis (IPF). The lung cancer incidences in these patients have not been investigated, and thus, we aimed to evaluate them here. Methods ILD patients at our hospital were retrospectively reviewed. The cumulative incidences of lung cancer in patients with various ILDs were estimated with Kaplan-Meier curves and compared between ILD groups using log-rank tests. The association between several variables at initial diagnosis and lung cancer development was assessed with Cox proportional hazards regression analysis to identify predictors. Results In all, 606 ILD patients, including 161 with IPF, 133 with non-IPF idiopathic interstitial pneumonias, 160 with chronic hypersensitivity pneumonitis, 87 with connective tissue disease-related ILDs, 19 with pulmonary sarcoidosis, and 46 with other ILDs, were included. Twenty-eight patients developed lung cancer. The cumulative incidences of lung cancer at 1, 3, and 5 years were: 1.9, 5.7, and 12.3% with IPF, respectively; 0.8, 0.8, and 4.0% in non-IPF idiopathic interstitial pneumonias; 2.0, 4.6, and 11.0% in chronic hypersensitivity pneumonitis; and 1.1, 1.1, and 2.9% in connective tissue disease-related ILDs. IPF patients had a higher incidence of lung cancer than non-IPF idiopathic interstitial pneumonia patients (p = 0.036). A radiological usual interstitial pneumonia pattern, forced vital capacity value, and pack-years were associated with lung cancer development (hazard ratios 2.959, 1.031, 1.011; 95% confidence intervals 1.257–6.963, 1.006–1.057, 1.002–1.020, p = 0.013, 0.017, 0.020, respectively). Conclusions The lung cancer incidence is higher in IPF patients than in non-IPF idiopathic interstitial pneumonia patients and is equally high in patients with chronic hypersensitivity pneumonitis and IPF.

BackgroundRisk factors for COPD in high-income settings are well understood; however, less attention has been paid to contributors of COPD in low-income and middle-income countries (LMICs) such as pulmonary tuberculosis. We sought to study the association between previous tuberculosis disease and COPD by using pooled population-based cross-sectional data in 13 geographically diverse, low-resource settings.MethodsWe pooled six cohorts in 13 different LMIC settings, 6 countries and 3 continents to study the relationship between self-reported previous tuberculosis disease and lung function outcomes including COPD (defined as a postbronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) below the lower limit of normal). Multivariable regressions with random effects were used to examine the association between previous tuberculosis disease and lung function outcomes.ResultsWe analysed data for 12 396 participants (median age 54.0 years, 51.5% male); 332 (2.7%) of the participants had previous tuberculosis disease. Overall prevalence of COPD was 8.8% (range 1.7%–15.5% across sites). COPD was four times more common among those with previous tuberculosis disease (25.7% vs 8.3% without previous tuberculosis disease, p1(−0.70, 95% CI −0.84 to −0.55), FVC (−0.44, 95% CI −0.59 to −0.29) and the FEV1:FVC ratio (−0.63, 95% CI −0.76 to −0.51) when compared with those without previous tuberculosis disease.ConclusionsPrevious tuberculosis disease is a significant and under-recognised risk factor for COPD and poor lung function in LMICs. Better tuberculosis control will also likely reduce the global burden of COPD.

Background Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain atrophy in patients with acute ischemic stroke due to large vessel occlusion. Methods We used data from MR CLEAN, a multicenter trial including patients with acute ischemic stroke due to anterior circulation large vessel occlusion randomized to endovascular treatment plus medical care (intervention) versus medical care alone (control). We segmented total brain volume (TBV) and intracranial volume (ICV) on baseline non-contrast computed tomography (n = 410). Next, we determined the degree of atrophy as the proportion of brain volume in relation to head size (1 − TBV/ICV) × 100%, analyzed as continuous variable and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale expressed as adjusted common odds ratio. Treatment effect modification was tested using an interaction term between brain atrophy (as continuous variable) and treatment allocation. Results We found that brain atrophy significantly modified the effect of endovascular treatment on functional outcome (P for interaction = 0.04). Endovascular treatment led to larger shifts towards better functional outcome in the higher compared to the lower range of atrophy (adjusted common odds ratio, 1.86 [95% CI: 0.97–3.56] in the lowest tertile vs. 1.97 [95% CI: 1.03–3.74] in the middle tertile vs. 3.15 [95% CI: 1.59–6.24] in the highest tertile). Conclusion Benefit of endovascular treatment is larger in the higher compared to the lower range of atrophy, demonstrating that advanced atrophy should not be used as an argument to withhold endovascular treatment.

BackgroundMental pain has been proposed as a global person-centered outcome measure. The aim of this cross-sectional study was to test an essential requisite of such a measure, namely that mental pain incorporates independent contributions from a range of discrete but disparate outcome measures.MethodsTwo hundred migraine patients were assessed concerning migraine disability, psychosomatic syndromes, mental pain, depression, anxiety, and psychosocial dimensions. General linear models were tested to verify which measures would individually make unique contributions to overall mental pain.ResultsThe final model, accounting for 44% of variance, identified that higher mental pain was associated with more severe depressive symptoms, higher migraine disability, lower well-being, and poorer quality of life.ConclusionIn this sample, mental pain was shown to behave as expected of a global outcome measure, since multiple measures of symptomatology and quality of life showed modest but significant bivariate correlations with mental pain and some of these measures individually made unique contributions to overall mental pain.

Rationale, aims and objectives: Patient-centered care is considered a vital component of good quality care for breast cancer patients. Nevertheless, the implementation of this valuable concept in clinical practice appears to be difficult. The goal of this study is to bridge the gap between theoretical elaboration of “patient-centered care” and clinical practice. To that purpose, a scoping analysis was performed of the application of the term “patient-centered care in breast cancer treatment” in present-day literature. Method: For data-extraction, a literature search was performed extracting references that were published in 2018 and included the terms “patient-centered care” and “breast cancer”. The articles were systematically traced for answers to the following three questions: “What is patient-centered care?”, “Why perform patient-centered care?”, and “How to realize patient-centered care?”. For the content analysis, these answers were coded and assembled into meaningful clusters until separate themes arose which concur with various interpretations of the term “patient-centered care”. Results: A total of 60 publications were retained for analysis. Traced answers to the three questions “what”, “why”, and “how” varied considerably in recent literature concerning breast cancer treatment. Despite the inconsistent use of the term “patient-centered care,” we did not find any critical consideration about the nature of the concept, regardless of the applied interpretation. Interventions that are supposed to contribute to the heterogeneous concept of patient-centered care as such, seem to be judged desirable, virtually without empirical justification. Conclusions: We propose, contrary to previous efforts to define “patient-centered care” more accurately, to embrace the heterogeneity of the concept and apply “patient-centered care” as an umbrella-term for all healthcare that intends to contribute to the acknowledgement of the person in the patient. For the justification of measures to realize patient-centered care for breast cancer patients, instead of a mere contribution to the abstract concept, we insist on the demonstration of desirable real-world effects.

Background:The Utrecht Scale for Evaluation of Rehabilitation-Participation Restrictions scale (USER-P-R) is a promising patient-reported outcome measure, but has currently not been validated in a hospital-based stroke population. Objective:To examine psychometric properties of the USER-P-R in a hospital-based stroke population 3 months after stroke onset. Methods:Cross-sectional study including 359 individuals with stroke recruited through 6 Dutch hospitals. The USER-P-R, EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5 L), Patient Reported Outcomes Measurement Information System 10-Question Global Health Short Form (PROMIS-10), modified Rankin Scale (mRS) and two items on perceived decrease in health and activities post-stroke were administered in a telephone interview 3 months after stroke. The internal consistency, distribution, floor/ceiling effects, convergent validity and discriminant ability of the USER-P-R were calculated. Results:Of all participants, 96.9% were living at home and 50.9% experienced no or minimal disabilities (mRS 0-1). The USER-P-R showed high internal consistency (alpha = 0.90) and a non-normal left-skewed distribution with a ceiling effect (21.4% maximum scores). A substantial proportion of participants with minimal disabilities (mRS 1) experienced restrictions on USER-P-R items (range 11.9-48.5%). The USER-P-R correlated strongly with the EQ-5D-5 L, PROMIS-10 and mRS. The USER-P-R showed excellent discriminant ability in more severely affected individuals with stroke, whereas its discriminant ability in less affected individuals was moderate. Conclusions:The USER-P-R shows good measurement properties and provides additional patient-reported information, proving its usefulness as an instrument to evaluate participation after 3 months in a hospital-based stroke population.

Study Design: A sex- and age-matched case-control study and a cross-sectional study. Objective: In our previous study, patients with early-onset (Methods: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. Results: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. Conclusions: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.

Objective: Intermetatarsal bursae in the forefeet possess a synovial lining similar to joints and tendon sheaths. Inflammation of these bursae (intermetatarsal bursitis [IMB]) was recently identified as specific for early rheumatoid arthritis (RA). The present study was undertaken to determine if IMB is indeed an RA feature by assessing the following: 1) the association with other local inflammatory measures (synovitis, tenosynovitis, and osteitis), 2) the association with clinical signs, and 3) whether it responds to disease-modifying antirheumatic drug (DMARD) therapy similarly to other local inflammatory measures. Methods: One hundred fifty-seven consecutive early RA patients underwent unilateral contrast-enhanced 1.5T forefoot magnetic resonance imaging (MRI) at diagnosis. MRIs were evaluated for IMB presence and for synovitis, tenosynovitis, and osteitis in line with the RA MRI Scoring (RAMRIS) system (summed as RAMRIS inflammation). MRIs at 4, 12, and 24 months were evaluated for IMB presence and size in patients who had IMB at baseline and received early DMARD therapy. Logistic regression and generalized estimating equations were used. Anti-citrullinated protein antibody (ACPA) stratification was performed. Results: Sixty-nine percent of RA patients had >= 1 IMB. In multivariable analysis on bursa level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis, with odds ratios (OR) of 1.69 (95% confidence interval [95% CI] 1.12, 2.57) and 2.83 (95% CI 1.80, 4.44), respectively, but not osteitis. On the patient level, IMB presence was most strongly associated with tenosynovitis (OR 2.92 [95% CI 1.62, 5.24]). IMB presence was associated with local joint swelling (OR 2.7 [95% CI 1.3, 5.3]) and tenderness (OR 1.7 [95% CI 1.04, 2.9]) independent of RAMRIS inflammation. During treatment, IMB size decreased between 0 and 12 months. This decrease associated with decrease in RAMRIS inflammation, which was driven by synovitis decrease. Within ACPA-positive and ACPA-negative RA, similar results were obtained. Conclusion: IMB particularly accompanies inflammation of the synovial lining of joints and tendon sheaths, showed a similar treatment response after DMARD initiation, and associates with typical clinical signs. These findings suggest that IMB represents a frequently present novel RA feature of juxtaarticular synovial inflammation.

Increased exposure to ultraviolet radiation (UVR) is associated with an increased risk of nonmelanoma skin cancer. Cutaneous surgery can be negatively influenced by UVR, causing delayed wound healing, hyperpigmentation of the scar, and an increased incidence of additional skin cancers. By changing sun protection behavior, these risks can be limited. Therefore, this study evaluates changes in patients' sun protective behavior after Mohs micrographic surgery (MMS). Patients undergoing MMS between December 2017 and November 2019 were included. Patients were asked to complete the FACE-Q Skin Cancer - Sun Protection Behavior checklist before and 3 months and 1 year post-surgery. A total of 125 patients completed the pre-operative and 3-months post-operative checklists, and 89 (71.2%) completed the 1-year post-operative checklist. Reported sun protective behaviors increased post-surgery at all time points (p < 0.001). Patients with a prior history of facial skin cancer demonstrated a larger increase in sun protection behaviors after surgery than patients without a history of facial skin cancer (p = 0.04). Patients with defects located on the ear or scalp demonstrated a lesser increase in sun protection behaviors than patients with defects located in more conspicuous areas as the face (p = 0.02). Our study demonstrates a change in sun protection behavior, with an increase in sun protection behavior over time in patients after MMS. However, more improvement is possible. Targeted counseling can increase sun protection behavior in patients without a history of facial skin cancer and patients with skin cancer located on the ears or scalp.

A 46-year old female patient presented with a left-sided superior temporal quadrantanopia due to a recurrent craniopharyngioma. The location of the recurrence was unusual. Imaging showed an enlarged left optic nerve, suggestive of a recurrent intra-optic craniopharyngioma. It was possible to remove the tumour without compromising the visual functions. In this report, we describe the case in further details.