Anorectal disorders are common in general practice and the incidence of chronic anal fissure is 2.5 cases per 1000 persons in the Netherlands. A chronic anal fissure (CAF) refers to a longitudinal... Show moreAnorectal disorders are common in general practice and the incidence of chronic anal fissure is 2.5 cases per 1000 persons in the Netherlands. A chronic anal fissure (CAF) refers to a longitudinal ulcer or tear in the squamous epithelium, generally located in the posterior midline with symptoms present for longer than 4-6 weeks or recurrent fissures. The classical symptom is pain during defecation, which may persist for hours, and has a significant impact on quality of life.Although some debate exists on the pathogenesis of CAF, it is assumed that pain causes an increased anal sphincter tone leading to ischemia which inhibits fissure healing, generating a vicious circle of pain and constipation.Pelvic floor dysfunction e.g., dyssynergia and/or increased pelvic floor muscle tone may also be an underlying cause and part of the pathophysiology and a reason for unresponsiveness to treatment.A digital rectal examination including examination of the pelvic floor muscles and a comprehensive evaluation of the pelvis and surrounding structures is important to determine the underlying cause of pain and pelvic floor dysfunction.According to current guidelines, the initial conservative management is comprised of fibre intake and/or use of laxatives, toilet behaviour, lifestyle advice, sitz baths, and ointments.In the Pelvic floor Anal Fissure (PAF) study, we demonstrated that pelvic floor physical therapy yields a significant and clinical benefit in the time course and should be advocated as adjuvant conservative treatment in patients with CAF. Show less
AimTreatment for cluster headache is currently based on a trial-and-error approach. The available preventive treatment is unspecific and based on few and small studies not adhering to modern... Show moreAimTreatment for cluster headache is currently based on a trial-and-error approach. The available preventive treatment is unspecific and based on few and small studies not adhering to modern standards. Therefore, the authors collaborated to discuss acute and preventive treatment in cluster headache, addressing the unmet need of safe and tolerable preventive medication from the perspectives of people with cluster headache and society, headache specialist and cardiologist.FindingsThe impact of cluster headache on personal life is substantial. Mean annual direct and indirect costs of cluster headache are more than 11,000 Euros per patient. For acute treatment, the main problems are treatment response, availability, costs and, for triptans, contraindications and the maximum use allowed. Intermediate treatment with steroids and greater occipital nerve blocks are effective but cannot be used continuously. Preventive treatment is sparsely studied and overall limited by relatively low efficacy and side effects. Neurostimulation is a relevant option for treatment-refractory chronic patients. From a cardiologist’s perspective use of verapamil and triptans may be worrisome and regular follow-up is essential when using verapamil and lithium.ConclusionWe find that there is a great and unmet need to pursue novel and targeted preventive modalities to suppress the horrific pain attacks for people with cluster headache. Show less
Krijbolder, D.I.; Khidir, S.J.H.; Helm-van Mil, A.H.M. van der 2023
Objectives While awaiting therapies accomplishing rheumatoid arthritis (RA)-prevention in individuals at-risk, recent evidence supports that a 1-year methotrexate treatment may lead to sustained... Show moreObjectives While awaiting therapies accomplishing rheumatoid arthritis (RA)-prevention in individuals at-risk, recent evidence supports that a 1-year methotrexate treatment may lead to sustained reduction in disease burden and subclinical joint inflammation in patients with clinically suspect arthralgia (CSA). We aimed to study the previously unexplored attitudes of CSA patients and rheumatologists on 1-year DMARD treatment in the arthralgia phase to reduce the disease burden, while not preventing RA.Methods CSA patients who participated in the TREAT EARLIER trial, thus being expert by experience, were informed on the trial results. Thereafter they completed an anonymous questionnaire about their attitudes on treatment in the CSA phase. We used the same approach for Dutch healthcare professionals in rheumatology.Results The majority of trial participants (85%) considered the effects of the 1-year treatment as found in the TREAT EARLIER trial, beneficial in the symptomatic at-risk stage. 79% would recommend a 1-year methotrexate course to others with comparable joint complaints. Two-thirds indicated RA prevention and improving disease burden to be equally important treatment goals in the CSA phase. Most healthcare professionals (88%) were inclined to prescribe 1-year treatment to CSA patients aimed at long-term improvement of symptoms and functioning, while not preventing RA development. 59% believed the profits of a 1-year methotrexate course to outweigh disadvantages, for example, side effects.Conclusions A considerable willingness exists among CSA patients and rheumatologists to start a 1-year treatment resulting in long-term improvement of symptoms and functioning, while not preventing RA. This emphasises the need for more research optimising treatment regimens and disease monitoring in individuals at-risk to facilitate such treatment decisions in the future, while avoiding an intervention, either limited or for a prolonged period, which may have harms that outweigh benefits. Show less
BackgroundChronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition... Show moreBackgroundChronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans.MethodsA primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring.Results36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNF & alpha;), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNF & alpha; and were considered the most effective treatments.ConclusionsFollowing from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNF & alpha; are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline. Show less
Plasma cells are the antibody secretors of the immune system. Continuous antibody secretion over years can provide long-term immune protection but could also be held responsible for long-lasting... Show morePlasma cells are the antibody secretors of the immune system. Continuous antibody secretion over years can provide long-term immune protection but could also be held responsible for long-lasting autoimmunity in case of self-reactive plasma cells. Systemic autoimmune rheumatic diseases (ARD) affect multiple organ systems and are associated with a plethora of different autoantibodies. Two prototypic systemic ARDs are systemic lupus erythematosus (SLE) and Sjögren's disease (SjD). Both diseases are characterized by B-cell hyperactivity and the production of autoantibodies against nuclear antigens. Analogues to other immune cells, different subsets of plasma cells have been described. Plasma cell subsets are often defined dependent on their current state of maturation, that also depend on the precursor B-cell subset from which they derived. But, a universal definition of plasma cell subsets is not available so far. Furthermore, the ability for long-term survival and effector functions may differ, potentially in a disease-specific manner. Characterization of plasma cell subsets and their specificity in individual patients can help to choose a suitable targeting approach for either a broad or more selective plasma cell depletion. Targeting plasma cells in systemic ARDs is currently challenging because of side effects or varying depletion efficacies in the tissue. Recent developments, however, like antigen-specific targeting and CAR-T-cell therapy might open up major benefits for patients beyond current treatment options. Show less
Bruni, C.; Campochiaro, C.; Vries-Bouwstra, J.K. de 2023
Background: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown.Aim: To compare the awareness and... Show moreBackground: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown.Aim: To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019.Methods: Hospital sites and their associated community practices across 12 European countries completed an online survey in 2018-2019, to report on their practices in terms of surveillance, prevention, diagnosis, and treatment of CDI. Responses were collected from 105 hospitals and 39 community general practitioners (GPs).Findings: Hospital sites of 11 countries reported participation in national surveillance schemes compared with six countries for international schemes. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID)-recommended CDI testing meth-odologies were used by 82% (86/105) of hospitals, however countries reporting the highest incidence of CDI used non-recommended tests. Over 75% (80/105) of hospitals were aware of the most recent European CDI treatment guidelines at the time of this survey compared with only 26% (10/39) of surveyed GPs. However, up to 15% (16/105) of hospitals reported using the non-recommended metronidazole for recurrent CDI cases, sites in countries with lower awareness of CDI treatment guidelines. Only 37% (39/105) of hospitals adopted contact isolation precautions in case of suspected CDI.Conclusion: Good awareness of guidelines for the management of CDI was observed across the surveyed European hospital sites. However, low compliance with diagnostic testing guidelines, infection control measures for suspected CDI, and insufficient awareness of treatment guidelines continued to be reported in some countries. 2022 The Author(s). Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Meeuwes, F.O.; Brink, M.; Poel, M.W.M. van der; Kersten, M.J.; Wondergem, M.; Mutsaers, P.G.N.J.; ... ; Nijland, M. 2022
Background: Patients with angioimmunoblastic T-cell lymphoma (AITL) are treated with cyclophosphamide, doxorubicin, vincristine and prednisone with or without etoposide (CHO(E)P). In the majority... Show moreBackground: Patients with angioimmunoblastic T-cell lymphoma (AITL) are treated with cyclophosphamide, doxorubicin, vincristine and prednisone with or without etoposide (CHO(E)P). In the majority of cases, Epstein-Barr virus (EBV)-positive B-cells are present in the tumour. There is paucity of research examining the effect of rituximab when added to CHO(E)P. In this nationwide, population-based study, we analysed the impact of rituximab on overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) of patients with AITL. Methods: Patients with AITL diagnosed between 2014 and 2020 treated with >one cycle of CHO(E)P with or without rituximab were identified in the Netherlands Cancer Registry. Sur-vival follow-up was up to 1st February 2022. Baseline characteristics, best response during first-line treatment and survival were collected. PFS was defined as the time from diagnosis to relapse or to all-cause-death. OS was defined as the time from diagnosis to all-cause-death. Multivariable analysis for the risk of mortality was performed using Cox regression. Findings: Out of 335 patients, 146 patients (44%) received R-CHO(E)P. Rituximab was more frequently used in patients with a B-cell infiltrate (71% versus 89%, p < 0.01). The proportion of patients who received autologous stem cell transplantation (ASCT) was similar between CHO(E)P and R-CHO(E)P (27% versus 30%, respectively). The ORR and 2-year PFS for pa-tients who received CHO(E)P and R-CHO(E)P were 71% and 78% (p = 0.01), and 40% and 45% (p = 0.12), respectively. The 5-year OS was 47% and 40% (p = 0.99), respectively. In multi -variable analysis, IPI-score 3-5, no B-cell infiltrate and no ASCT were independent prognostic factors for risk of mortality, whereas the use of rituximab was not. Interpretation: Although the addition of rituximab to CHO(E)P improved ORR for patients with AITL, the PFS and OS did not improve. 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Aims To develop a suite of quality indicators (QIs) for the management of patients with ventricular arrhythmias (VA) and the prevention of sudden cardiac death (SCD). Methods and results The... Show moreAims To develop a suite of quality indicators (QIs) for the management of patients with ventricular arrhythmias (VA) and the prevention of sudden cardiac death (SCD). Methods and results The Working Group comprised experts in heart rhythm management including Task Force members of the 2022 European Society of Cardiology (ESC) Clinical Practice Guidelines for the management of patients with VA and the prevention of SCD, members of the European Heart Rhythm Association, international experts, and a patient representative. We followed the ESC methodology for QI development, which involves (i) the identification of the key domains of care for the management of patients with VA and the prevention of SCD by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. We identified eight domains of care for the management of patients with VA and the prevention of SCD: (i) structural framework, (ii) screening and diagnosis, (iii) risk stratification, (iv) patient education and lifestyle modification, (v) pharmacological treatment, (vi) device therapy, (vii) catheter ablation, and (viii) outcomes, which included 17 main and 4 secondary QIs across these domains. Conclusion Following a standardized methodology, we developed 21 QIs for the management of patients with VA and the prevention of SCD. The implementation of these QIs will improve the care and outcomes of patients with VA and contribute to the prevention of SCD. Show less
Background: A chronic anal fissure is a common, painful condition with great impact on daily life. The exact pathogenesis has not been fully elucidated and treatment varies. A large percentage of... Show moreBackground: A chronic anal fissure is a common, painful condition with great impact on daily life. The exact pathogenesis has not been fully elucidated and treatment varies. A large percentage of patients experience pelvic floor dysfunction (dyssynergia and increased pelvic floor muscle tone). The aim of our study was to investigate the effect of pelvic floor physical therapy in patients with chronic anal fissure. Methods: Between December 2018 and July 2021, at the Proctos Clinic in the Netherlands, patients with chronic anal fissure and pelvic floor dysfunction were randomly assigned to an intervention group, receiving 8 weeks of pelvic floor physical therapy including electromyographic biofeedback or assigned to a control group receiving postponed pelvic floor physical therapy. The primary outcome was muscle tone at rest during electromyographic registration of the pelvic floor before and after pelvic floor physical therapy. Secondary outcomes contained healing of the fissure, pain ratings, improvement of pelvic floor function, and complaint reduction measured with a proctology-specific patient-reported outcome measurement. Endpoints were measured at 8- and 20-week follow-up. Results: One hundred forty patients were included in the study, 68 men (48.6%) and 72 women (51.4%) with a mean age of 44.5 +/- 11.1 (range 19-79) years. Mean resting electromyographic values of the pelvic floor in the intervention group significantly improved from pre- to post-treatment (p < 0.001) and relative to controls (mean estimated difference between groups - 1.88 mu V; 95% CI, - 2.49 to - 1.27 (p < 0.001) at first follow-up and remained significant from baseline at 20-week follow-up (p < 0.001). The intervention group performed better compared to the control group on all secondary outcomes, i.e., healing of the fissure (55.7% of the patients vs 21.4% in control, pain ratings (p < 0.001), diminished dyssynergia (p < 0.001), complaint reduction (p < 0.001), and decrease of pelvic floor muscle tone (p < 0.05) at first follow-up. Conclusions: The findings of this study provide strong evidence that pelvic floor physical therapy is effective in patients with chronic anal fissure and pelvic floor dysfunction and supports its recommendation as adjuvant treatment besides regular conservative treatment. Show less
Background Chronic anal fissure (CAF) is a common, bothersome condition frequently accompanied by pelvic floor complaints. Despite current guidelines, optimal management is challenging. The aim of... Show moreBackground Chronic anal fissure (CAF) is a common, bothersome condition frequently accompanied by pelvic floor complaints. Despite current guidelines, optimal management is challenging. The aim of this study is to evaluate current management of CAF among gastrointestinal surgeons in the Netherlands. Methods Dutch gastrointestinal surgeons and residents were sent a survey invitation by email, which was available online between June 2021 and September 2021. The questionnaire consisted of 21 questions concerning work experience, physical examination, diagnostic and surgical techniques, and follow-up. Results Overall, 106 (33%) respondents completed the survey. Most respondents (59%) had at least 10 years of experience in treating CAF. Only 23% always addressed pelvic floor complaints. Fifty-one percent performed digital rectal examination and 22% always, or almost always, examined the pelvic floor muscles. Most respondents started treatment with fibers and/or laxatives and ointment (96%). Diltiazem was in 90% the preferred ointment. Twenty-two percent referred patients for pelvic floor physical therapy. Botulinum toxin was in 54% performed under general or spinal anesthesia or sedation. The surgical procedure of choice was fissurectomy (71%) followed by lateral internal sphincterotomy (27%). Fissurectomy was in 51% always combined with botulinum toxin. Fifty-seven percent of the respondents preferred a physical follow-up appointment. Conclusion Guideline recommendations are largely followed in the Netherlands, starting with conservative measures followed by surgical procedures. Surgeons do not consistently assess pelvic floor complaints, nor do they routinely examine the pelvic floor muscles. Awareness of pelvic floor dysfunctions is important to refer patients for pelvic floor physical therapy. Show less
Purpose: The best treatment of humeral shaft fractures in adults is still under debate. This study aimed to compare functional and clinical outcome of operative versus nonoperative treatment in... Show morePurpose: The best treatment of humeral shaft fractures in adults is still under debate. This study aimed to compare functional and clinical outcome of operative versus nonoperative treatment in adult patients with a humeral shaft fracture. We hypothesized that operative treatment would result in earlier functional recovery. Methods: From October 23, 2012 to October 03, 2018, adults with a humeral shaft fracture AO type 12A or 12B were enrolled in a prospective cohort study in 29 hospitals. Patients were treated operatively or nonoperatively. Outcome measures were the Disabilities of the Arm, Shoulder, and Hand score (DASH; primary outcome), Constant-Murley score, pain (Visual Analog Score, VAS), health-related quality of life (Short Form-36 (SF-36) and EuroQoL-5D-3L (EQ-5D)), activity resumption (Numeric Rating Scale, NRS), range of motion (ROM) of the shoulder and elbow joint, radiologic healing, and complications. Patients were followed for one year. Repeated measure analysis was done with correction for age, gender, and fracture type. Results: Of the 390 included patients, 245 underwent osteosynthesis and 145 were primarily treated nonoperatively. Patients in the operative group were younger (median 53 versus 62 years; p < 0.001) and less frequently female (54.3% versus 64.8%; p = 0.044). Superior results in favor of the operative group were noted until six months follow-up for the DASH, Constant-Murley, abduction, anteflexion, and external rotation of the shoulder, and flexion and extension of the elbow. The EQ-US, and pronation and supination showed superior results for the operative group until six weeks follow-up. Malalignment occurred only in the nonoperative group (N = 14; 9.7%). In 19 patients with implant-related complications (N = 26; 10.6%) the implant was exchanged or removed. Nonunion occurred more often in the nonoperative group (26.3% versus 10.10% in the operative group; p < 0.001). Conclusion: Primary osteosynthesis of a humeral shaft fracture (AO type 12A and 12B) in adults is safe and superior to nonoperative treatment, and should therefore be the treatment of choice. It is associated with a more than twofold reduced risk of nonunion, earlier functional recovery and a better range of motion of the shoulder and elbow joint than nonoperative treatment. Even after including the implant-related complications, the overall rate of complications as well as secondary surgical interventions was highest in the nonoperative group. Show less
Mahe, G.; Brodmann, M.; Capodanno, D.; Ceriello, A.; Cuisset, T.; Delgado, V.; ... ; Valensi, P. 2022
Aims: This survey aimed to evaluate the current management and screening of coronary artery disease and peripheral artery disease in people with type 2 diabetes mellitus (T2DM) in Europe, utilizing... Show moreAims: This survey aimed to evaluate the current management and screening of coronary artery disease and peripheral artery disease in people with type 2 diabetes mellitus (T2DM) in Europe, utilizing the 2013 ESC/EASD (European Society of Cardiology/European Association for the Study of Diabetes) guidelines as a benchmark. Methods: The PADDIA/CADDIA survey is a European medical research collaboration targeting cardiologists, vascular physicians, diabetologists and general practitioners from Austria, Belgium, France, Germany, Italy, Netherlands and United Kingdom. Results: The questionnaire was completed by sixty-three physicians, of whom 75% declared assessing the cardiovascular risk of people with T2DM mostly without using a risk score (59%). More than 90% of the panel, check HbA1c, blood pressure and low-density lipoprotein cholesterol targets in their patients with T2DM and coronary or peripheral artery disease. For 94% the presence of T2DM influence their patients' management, by optimizing blood glucose, blood pressure and low-density lipoprotein cholesterol control. Only 37% considered screening for lower extremity peripheral artery disease among their T2DM patients and 35% among those with cardiovascular disease. Conclusions: Physicians mostly follow the ESC/EASD 2013 guidelines, but when it comes to screening for additional conditions including coronary artery disease or peripheral artery disease, or intensifying the antithrombotic regimen there is need for better guidance. (C) 2022 Elsevier B.V. All rights reserved. Show less
OBJECTIVES: Persistent air leak (PAL; >5days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity.... Show moreOBJECTIVES: Persistent air leak (PAL; >5days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity. Literature is contradictory about the prevention and treatment of PAL. Variation is therefore hypothesized. The aim of this study is to understand the variation in the incidence, preventive management and treatment of PAL.METHODS: Data from the Dutch Lung Cancer Audit for Surgery were combined with results of an online survey among Dutch thoracic surgeons. The national incidence of PAL and case-mix corrected between-hospital variation were calculated in patients who underwent an oncological (bi)lobectomy or segmentectomy between January 2012 and December 2018. By multivariable logistic regression, factors associated with PAL were assessed. A survey was designed to assess variation in (preventive) management and analysed using descriptive statistics. Hospital-level associations between management strategies and PAL were assessed by univariable linear regression.RESULTS: Of 12382 included patients, 9.0% had PAL, with a between-hospital range of 2.6-19.3%. Factors associated with PAL were male sex, poor lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidity, upper lobe resection, (bi)lobectomy (vs segmentectomy), right-sided tumour and robotic-assisted thoracic surgery. Perioperative (preventive) management of PAL differed widely between hospitals. When using water seal compared to suction drainage, the average incidence of PAL decreased 2.9%.CONCLUSIONS: In the Netherlands, incidence and perioperative (preventive) management of PAL vary widely. Using water seal instead of suction drainage and increasing awareness are potential measures to reduce this variation. Show less
Eshuis, L.V.; Gelderen, M.J. van; Zuiden, M. van; Nijdam, M.J.; Vermetten, E.; Olff, M.; Bakker, A. 2021
Background: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD... Show moreBackground: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD) treatment by increasing a patient's sense of presence during exposure therapy. This study aimed to systematically review current evidence regarding the efficacy of VRET and ARET as PTSD treatment. Methods: A systematic electronic database search, a systematic quality assessment and two meta-analyses were conducted in accordance with PRISMA guidelines. Results: Eleven studies on the efficacy of VRET for PTSD (n = 438) were found, but no studies on the efficacy of ARET. The majority of VRET studies were of a low quality and had heterogeneous results. Meta-analyses showed VRET outperformed waitlist control (standardized mean difference -0.64 (95% CI -1.05 to -0.22)) while no significant difference was found between VRET and active treatment conditions (standardized mean difference -0.25 (95% CI -0.77 to 0.27)). Conclusion: VRET was superior to waitlist control groups and as effective as other psychotherapies. However, the results showed considerable heterogeneity due to the low number of studies and variety of VRET methods. VRET may be an effective alternative to current treatments and shows promise for the treatment of PTSD patients that have not responded to previous treatment. Future research should focus on high quality RCTs, including information on side effects and adverse events, with sufficient numbers of participants. This study recognizes a research gap regarding the efficacy of ARET, while it may have potential for PTSD treatment. Show less
Even after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The... Show moreEven after thousands of years of experience in treating patients with TBI, decisions regarding the optimal treatment strategy remain difficult for both healthcare workers as policy makers. The first part of this thesis investigated the challenges of the treatment decision-making process in patients with (severe) TBI by focussing on three factors considered to be important in this process: patient outcome, in-hospital healthcare consumption, and in-hospital costs. The second part investigated the procedural difficulties in TBI research efficiency by focussing on the process of institutional review board approval and the use of informed consent procedures in patients with TBI with an inability to provide informed consent. Finally, we elaborate on the role of patient outcome and in-hospital costs in the acute treatment decision-making process in patients with severe TBI and make suggestions to optimize future research initiatives. Show less
Versluis, J.M.; Hendriks, A.M.; Weppler, A.M.; Brown, L.J.; Joode, K. de; Suijkerbuijk, K.P.M.; ... ; Jalving, M. 2021
Introduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with... Show moreIntroduction: In patients with metastatic melanoma, progression of a single tumour lesion (solitary progression) after response to immune checkpoint inhibition (ICI) is increasingly treated with local therapy. We evaluated the role of local therapy for solitary progression in melanoma.Patients and methods: Patients with metastatic melanoma treated with ICI between 2010 and 2019 with solitary progression as first progressive event were included from 17 centres in 9 countries. Follow-up and survival are reported from ICI initiation.Results: We identified 294 patients with solitary progression after stable disease in 15%, partial response in 55% and complete response in 30%. The median follow-up was 43 months; the median time to solitary progression was 13 months, and the median time to subsequent progression after treatment of solitary progression (TTSP) was 33 months. The estimated 3-year overall survival (OS) was 79%; median OS was not reached. Treatment consisted of systemic therapy (18%), local therapy (36%), both combined (42%) or active surveillance (4%). In 44% of patients treated for solitary progression, no subsequent progression occurred. For solitary progression during ICI (n = 143), the median TTSP was 29 months. Both TTSP and OS were similar for local therapy, ICI continuation and both combined. For solitary progression post ICI (n = 151), the median TTSP was 35 months. TTSP was higher for ICI recommencement plus local therapy than local therapy or ICI recommencement alone (p = 0.006), without OS differences.Conclusion: Almost half of patients with melanoma treated for solitary progression after initial response to ICI had no subsequent progression. This study suggests that local therapy can benefit patients and is associated with favourable long-term outcomes. & ordf;2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Lelie-van der Zande, R.; Koster, E.S.; Teichert, M.; Bouvy, M.L. 2021
Background The Dutch general practitioners (GP) guideline for urinary tract infections (UTI) recommends patient-initiated treatment for women with recurring UTI. In countries other than the... Show moreBackground The Dutch general practitioners (GP) guideline for urinary tract infections (UTI) recommends patient-initiated treatment for women with recurring UTI. In countries other than the Netherlands, community pharmacists play a role in dispensing antibiotics for recurring UTI without preceding GP consultation. Objective To study GP and pharmacist opinions regarding the desirability of patient-initiated treatment, including potential pharmacist support for, and consequences of, facilitated access to antibiotics. Setting Dutch community pharmacies that cooperate with at least two GPs in their regional primary care network. Method Pharmacists in a postgraduate education program invited their residency pharmacist and 2-3 GPs to anonymously complete an online questionnaire. Questions related to diagnosis, treatment and potential role of the pharmacist. Answers were formulated as multiple-choice or ratings on a 5-point Likert scale. Data were analysed per professional group using descriptive statistics. Answers of pharmacists and GP to corresponding questions were analysed using a Chi-square test (p < 0.05). Main outcome measure Desirability of patient-initiated treatment and supporting role of the pharmacist. Results A total of 170 GPs and 76 pharmacists completed the questionnaires. Of the GPs, 35.1% supported patient-initiated treatment. Of the pharmacists, 69.7% were willing to dispense an antibiotic to a patient without preceding GP consultation after performing a probability check. In total, 65.7% of GPs and 44.7% of pharmacists thought that facilitated access to antibiotics would increase use of antibiotics (p < 0.05). Conclusion Support of GPs for facilitated access to antibiotic treatment by patient-initiated UTI treatment was limited, even with pharmacist support. The majority of pharmacists were willing to dispense an antibiotic after a probability check of an episode of recurring UTI, but both pharmacists and GPs were concerned about overuse of antibiotics. Show less
Boer, F.L.; Eikelder, M.L.G. ten; Geloven, N. van; Kapiteijn, E.H.; Gaarenstroom, K.N.; Hughes, G.; ... ; Poelgeest, M.I.E. van 2021
Objective. To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). Materials & methods. This... Show moreObjective. To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). Materials & methods. This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. Results. The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-riskclinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40?56%) and 31% (95% CI 23?39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. Conclusion. Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.Objective. To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM).Materials & methods. This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis.Results. The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-riskclinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno-or targeted therapy.Conclusion. Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Hoeboer, C.; Roos, C. de; Son, G.E. van; Spinhoven, P.; Elzinga, B. 2021
Background: Maltreatment by a primary caregiver is an important risk factor for the development of PTSD symptoms. Whereas meta-analyses indicate that parental emotional abuse is one of the most... Show moreBackground: Maltreatment by a primary caregiver is an important risk factor for the development of PTSD symptoms. Whereas meta-analyses indicate that parental emotional abuse is one of the most common forms of maltreatment, the impact of emotional abuse on PTSD symptoms and treatment effectiveness is still unclear, especially in children.Objective: We aimed to investigate the impact of parental emotional abuse on PTSD symptom severity and effectiveness of trauma treatment in children and adolescents.Method: In an outpatient sample (N = 287, mean age = 15.5 years), emotional abuse, index traumatic event, and PTSD symptoms were assessed at baseline. Thereafter, patients received evidence-based treatment for trauma-related symptoms embedded in a broader (systemic) treatment package. In a subsample (n = 130, mean age = 15.3 years) PTSD symptoms were assessed again 6 and 12 months after baseline.Results: Emotional abuse (rather than any other type of maltreatment) was associated with more severe PTSD symptoms in all symptom clusters. This was independent of whether emotional abuse was reported as index traumatic event or not. Moreover, PTSD symptoms were significantly reduced 6 months after the start of trauma-focused treatment, and emotional abuse was associated with more severe PTSD symptoms over the course of treatment.Conclusions: These findings underline the detrimental nature of emotional maltreatment in the context of PTSD symptomatology and treatment effectiveness. This calls for routine assessment of parental emotional abuse in the diagnostic phase, even when this is not the reason of referral. Show less
