ABSTRACT
BACKGROUND: Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. METHODS AND ANALYSIS: This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. ETHICS AND DISSEMINATION: The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. LIMITATIONS: High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.
Subject(s)
Asthma , Bronchitis, Chronic , Humans , Fractional Exhaled Nitric Oxide Testing , Prospective Studies , Quality of Life , Breath Tests , Asthma/drug therapy , Nitric Oxide , Inflammation , Multicenter Studies as TopicABSTRACT
OBJECTIVE: Dysfunctional breathing often coexists with asthma and complicates asthma control, especially in difficult-to-treat asthma. Voice bubbling therapy (VBT) by a specialized speech therapist may influence the breathing pattern. This pilot study investigated the effect of voice bubbling therapy (VBT) in participants with difficult-to-treat asthma, who fulfilled criteria for dysfunctional breathing pattern. METHOD: Twenty-four patients were randomized between VBT and usual care (UC). VBT is blowing into a glass (resonance) tube (28 cm in length, 0.9 cm inner diameter) which ends in a bowl of water (1.5 litre). Lung function, capillary blood gas and questionnaires were measured at baseline, at 6 and 18 weeks of follow up. RESULTS: No difference in ACQ and quality of life was found after VBT compared to UC group. However, after six weeks of bubbling therapy, pCO2 levels measured in capillary blood gas were higher (baseline median (IQR) pCO2 = 33.00 (17.25 - 38.6) mmHg; week 6 pCO2 = 36.00 (29.00 - 42.3) mmHg) p = 0.01. Moreover, ΔpCO2 (baseline - 18 weeks of follow up) was significantly correlated with ΔAQLQ (rs = 0.78, p = 0.02). CONCLUSION: VBT in participants with difficult-to-treat asthma resulted in a higher average pCO2 level, indicating the treatment may improve hyperventilation. However, this did not improve asthma control or quality of life. VBT may have value for a better management of asthma related symptoms.
Subject(s)
Asthma , Vocal Cord Dysfunction , Asthma/diagnosis , Humans , Hyperventilation , Pilot Projects , Quality of LifeABSTRACT
Introduction: Severe eosinophilic asthma is an incapacitating disease. Mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, proved to be effective as an add-on therapy in patients with severe eosinophilic asthma. However, only data from randomized controlled trials are available and real world data are lacking.Methods: A retrospective observational longitudinal study was conducted in a real world cohort of patients with severe eosinophilic asthma treated with mepolizumab. The primary objective was to determine response rate, based on a global evaluation of treatment effectiveness by the treating pulmonologist. Secondary objectives were to assess exacerbation frequency, systemic maintenance glucocorticoid usage, Asthma Control Questionnaire (ACQ), lung function, and adverse events.Results: Seventy-eight patients were included. Treatment with mepolizumab was considered beneficial and was therefore continued in 75.6% of patients 12 months from the initiation of mepolizumab. The most common reason for drop-out was insufficient response. Secondary objectives: 12 months from the initiation of mepolizumab there was a decrease of 3.2 (CI 2.5-4.1; p < 0.001) severe asthma exacerbations per year, a decrease of ACQ of 0.80 points (CI 0.49-1.12; p < 0.001), and an increase of 3.7 (CI 0.3-7.2; p = 0.034) percent of predicted FEV1 compared to baseline. At baseline 51.3% of patients were treated with systemic glucocorticoid maintenance therapy, compared to 15.4% (p < 0.001) of patients 12 months from the initiation of mepolizumab. No serious adverse events considered to be related to mepolizumab were reported.Conclusion: This study confirms that mepolizumab add-on therapy is effective and safe in a real world cohort of patients with severe eosinophilic asthma.
Subject(s)
Anti-Asthmatic Agents/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Asthma/drug therapy , Pulmonary Eosinophilia/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Asthmatic Agents/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Asthma/physiopathology , Disease Progression , Drug Therapy, Combination , Female , Forced Expiratory Volume , Glucocorticoids/administration & dosage , Hospitalization/statistics & numerical data , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To investigate whether laparoscopic sacrohysteropexy (LSH) is non-inferior to vaginal sacrospinous hysteropexy (SSHP) in the surgical treatment of uterine prolapse. DESIGN: Multicentre randomised controlled, non-blinded non-inferiority trial. SETTING: Five non-university teaching hospitals in the Netherlands, one university hospital in Belgium. POPULATION: 126 women with uterine prolapse stage 2 or higher undergoing surgery without previous pelvic floor surgery. METHODS: Randomisation in a 1:1 ratio to LSH or SSHP, stratified per centre and severity of the uterine prolapse. The predefined inferiority margin was an increase in surgical failure rate of 10%. MAIN OUTCOME MEASURES: Primary outcome was surgical failure, defined as recurrence of uterine prolapse (POP-Q ≥ 2) with bothersome bulging/protrusion symptoms and/or repeat surgery or pessary at 12 months postoperatively. Secondary outcomes were anatomical recurrence (any compartment), functional outcome and quality of life. RESULTS: Laparoscopic sacrohysteropexy was non-inferior for surgical failure (n = 1, 1.6%) compared with SSHP (n = 2, 3.3%, difference -1.7%, 95% CI: -7.1 to 3.7) 12 months postoperatively. Overall, anatomical recurrences and quality of life did not differ. More bothersome symptoms of overactive bladder (OAB) and faecal incontinence were reported after LSH. Dyspareunia was more frequently reported after SSHP. CONCLUSION: Laparoscopic sacrohysteropexy was non-inferior to SSHP for surgical failure of the apical compartment at 12 months' follow up. Following LSH, bothersome OAB and faecal incontinence were more frequent, but dyspareunia was less frequent. TWEETABLE ABSTRACT: Laparoscopic sacrohysteropexy and vaginal sacrospinous hysteropexy have equally good short-term outcomes.
Subject(s)
Gynecologic Surgical Procedures/methods , Laparoscopy/methods , Uterine Prolapse/surgery , Aged , Female , Gynecologic Surgical Procedures/adverse effects , Humans , Laparoscopy/adverse effects , Middle Aged , Recurrence , Severity of Illness Index , Treatment Outcome , Uterine Prolapse/classificationABSTRACT
Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of <5% (range, <5%-18%). The mortality rate was 10.3% (n = 32); 68% of patients had a raised troponin at presentation conferring a sixfold increase in mortality compared with those with normal troponin levels (12.1% vs 2.0%, P = .04). Twenty-four percent had a reduced Glasgow Coma Score (GCS) at presentation with a ninefold increase in mortality (20% vs 2.2% for normal GCS at presentation, P < .0001). Mortality increased with higher anti-ADAMTS13 antibody levels and lower ADAMTS13 antigen levels. Those with antibody levels in the upper quartile (antibody >77%) had a mortality of 16.9% compared with 5.0% for the lowest quartile (antibody <20%) (P = .004). Those with an antigen level in the lowest quartile (antigen <1.5%) had a mortality of 18% compared with 3.8% for the highest quartile (antigen >11%) (P = .005). The synergistic effect of anti-ADAMTS13 IgG antibody in the upper quartile and ADAMTS13 antigen in the lowest quartile had the highest mortality of 27.3%. We conclude that both anti-ADAMTS13 IgG antibody and ADAMTS13 antigen levels correlate with outcome in TTP with increased cardiac and neurological involvement and increased mortality.
Subject(s)
ADAMTS13 Protein , Autoantibodies , Immunoglobulin G , Purpura, Thrombotic Thrombocytopenic , ADAMTS13 Protein/blood , ADAMTS13 Protein/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Autoantibodies/blood , Autoantibodies/immunology , Child , Disease-Free Survival , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Purpura, Thrombotic Thrombocytopenic/blood , Purpura, Thrombotic Thrombocytopenic/immunology , Purpura, Thrombotic Thrombocytopenic/mortality , Survival RateABSTRACT
RATIONALE: The European Position Paper on Sinusitis (EPOS) guidelines provide composite criteria to evaluate chronic rhinosinusitis (CRS) control, taking into consideration the severity of patients' symptoms, aspect of nasal mucosa and medical intake as parameters of CRS control. OBJECTIVES: To study the degree of CRS control using novel EPOS control criteria at 3-5 years after a functional endoscopic sinus surgery (FESS) and correlate these data to symptoms scores. METHODS: Adult CRS patients (n = 560) who had undergone bilateral FESS for chronic inflammatory sinonasal disease 3-5 years prior to the study were included. Patients received a postal questionnaire asking for control items according to EPOS control criteria, visual analogue scale (VAS) scores for total and individual sinonasal symptoms, sinonasal outcome test (SNOT)-22 and Short Form (SF)-36 questionnaires. MEASUREMENTS AND MAIN RESULTS: About 19.5% of CRS patients were well controlled, with 36.8% of patients being partly controlled and 43.7% uncontrolled. The levels of control corresponded to mean total VAS, SNOT-22 and SF-36 scores. Subgroup analysis revealed that female gender, aspirin intolerance and revision FESS were associated with higher prevalence of uncontrolled CRS, whereas allergy, asthma and smoking status did not alter the percentage of patients in each category of control. In 81 patients attending the outpatient clinic, nasal endoscopy changed classification in only four patients (4.9%). CONCLUSIONS: Based on the novel EPOS control criteria, at least 40% of CRS patients are uncontrolled at 3-5 years after FESS. Therefore, better treatment strategies leading to higher disease control are warranted in CRS care.
Subject(s)
Laparoscopy/adverse effects , Rhinitis/epidemiology , Rhinitis/etiology , Sinusitis/epidemiology , Sinusitis/etiology , Tertiary Care Centers , Adolescent , Adult , Aged , Belgium/epidemiology , Chronic Disease , Female , Humans , Male , Middle Aged , Paranasal Sinuses/surgery , Rhinitis/prevention & control , Sinusitis/prevention & control , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Hysterectomy is one of the most performed surgical procedures during lifetime. Almost 10 % of women who have had a hysterectomy because of prolapse symptoms, will visit a gynaecologist for a surgical correction of a vaginal vault prolapse thereafter. Vaginal vault prolapse can be corrected by many different surgical procedures. A Cochrane review comparing abdominal sacrocolpopexy to vaginal sacrospinous fixation considered the open abdominal procedure as the treatment of first choice for prolapse of the vaginal vault, although operation time and hospital stay is longer. Literature also shows that hospital stay and blood loss are less after a laparoscopic sacrocolpopexy compared to the abdominal technique. To date, it is unclear which of these techniques leads to the best operative result and the highest patient satisfaction. Prospective trials comparing vaginal sacrospinous fixation and laparoscopic sacrocolpopexy are lacking. The aim of this randomized trial is to compare the disease specific quality of life of the vaginal sacrospinous fixation and laparoscopic sacrocolpopexy as the treatment of vaginal vault prolapse. METHODS: We will perform a multicentre prospective randomized controlled trial. Women with a post-hysterectomy symptomatic, POP-Q stage ≥2, vaginal vault prolapse will be included. Participants will be randomized to the vaginal sacrospinous fixation group or the laparoscopic sacrocolpopexy group. Primary outcome is disease specific quality of life at 12 months follow-up. Secondary outcome will be the effect of the surgical treatment on prolapse related symptoms, sexual functioning, procedure related morbidity, hospital stay, post-operative recovery, anatomical results using the POP-Q classification after one and 5 years follow-up, type and number of re-interventions, costs and cost-effectiveness. Analysis will be performed according to the intention to treat principle and not as a per protocol analysis. With a power of 90% and a level of 0.05, the calculated sample size necessary is 96 patients. Taking into account 10% attrition, a number of 106 patients (53 in each arm) will be included. DISCUSSION: The SALTO-2 trial is a randomized controlled multicentre trial to evaluate whether the laparoscopic sacrocolpopexy or vaginal sacrospinous fixation is the first-choice surgical treatment in patients with a stage ≥2 vault prolapse. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR3977 ; Registered 28 April 2013.
Subject(s)
Colposcopy/methods , Gynecologic Surgical Procedures/methods , Hysterectomy/adverse effects , Laparoscopy/methods , Pelvic Organ Prolapse/surgery , Postoperative Complications/surgery , Adult , Clinical Protocols , Female , Humans , Length of Stay , Middle Aged , Netherlands , Paraspinal Muscles/surgery , Pelvic Organ Prolapse/etiology , Postoperative Complications/etiology , Prospective Studies , Sacrococcygeal Region/surgery , Treatment Outcome , Vagina/surgeryABSTRACT
BACKGROUND: Vitiligo is a common skin disorder causing depigmented macules that can impair a patient's quality of life. Currently, there are no standardized outcome measures to assess the degree of depigmentation. Moreover, there is limited knowledge on the measurement properties of outcome measures in vitiligo. OBJECTIVES: To assess the reliability and responsiveness of the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force assessment (VETFa), two well-described clinician-reported outcomes. METHODS: We included three vitiligo patient groups. In one group of 31 patients, the interobserver reliability was assessed by three observers. In 27 patients the intraobserver reliability was assessed by two repeated measures by one of the observers. To assess the responsiveness the repigmentation was calculated after 6 months of phototherapy in 33 patients and tested against hypotheses. RESULTS: The interobserver reliability was high for VASI [intraclass correlation coefficient (ICC) 0·93] and VETFa depigmentation (ICC 0·88). The intraobserver reliability was high for VASI (ICC 0·93) and VETFa depigmentation (ICC 0·97). The smallest detectable changes (SDCs) were 7·1% and 10·4% for interobserver reliability and 4·7% and 2·9% for intraobserver reliability in VASI and VETFa depigmentation, respectively. All four responsiveness hypotheses formulated a priori were confirmed. CONCLUSIONS: VASI and VETFa are reliable and responsive instruments to assess the degree of depigmentation in vitiligo. VASI and VETFa for depigmentation are potential instruments for vitiligo research in the future. However, for use in individual patient care, caution is needed when interpreting score changes in individual patients because of the relatively large SDC.
Subject(s)
Severity of Illness Index , Vitiligo/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Observer Variation , Sensitivity and Specificity , Young AdultABSTRACT
The management of antithrombotic therapy in the peri-operative setting is a common problem, balancing haemorrhagic risk with continued treatment and thrombotic risk when discontinued. High-quality evidence is lacking regarding the optimal approach for patients on oral anticoagulants or antiplatelet agents. This review discusses the available evidence for the management of patients on warfarin, non-vitamin K antagonist oral anticoagulant drugs, and antiplatelet therapy in the peri-operative setting. Bridging therapy for patients on warfarin should be considered for those at highest risk of thrombosis, whereas it may not be necessary for those on non-vitamin K antagonist oral anticoagulant drugs given the reduced time off anticoagulation and their more predictable pharmacokinetics. Aspirin can be continued for most procedures. Dual antiplatelet agents for patients with a recently inserted coronary artery stent should be continued if possible but decisions should be individualised and taken after multidisciplinary discussion.
Subject(s)
Fibrinolytic Agents/therapeutic use , Perioperative Care , Angioplasty, Balloon, Coronary , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Fibrinolytic Agents/adverse effects , Heart Valve Prosthesis/adverse effects , Hemorrhage/etiology , Humans , Platelet Aggregation Inhibitors/therapeutic use , Stents , Thrombosis/etiologyABSTRACT
BACKGROUND: Vitiligo is a common depigmenting skin disorder that can influence a patient's quality of life. Although patient-orientated medicine is an emerging concept, a self-assessment tool to assess the degree of depigmentation in vitiligo is not yet available. Therefore, we developed the SAVASI, a self-assessment tool that uses the same basic principles as the VASI. OBJECTIVE: To assess the validity, reliability and acceptability of the SAVASI. METHODS: To assess the validity of the SAVASI, we compared the scores assessed by the patient with the scores of the VASI assessed by the physician. To assess the intra-rater reliability, the correlation between the baseline SAVASI and the SAVASI after 2 weeks was calculated. To assess the acceptability, patients indicated the time needed to complete the SAVASI and the patient assessed the difficulty of the questionnaire on a five-point scale. The Skindex-29 was used to determine the quality of life. The overestimation of the SAVASI compared to the VASI was calculated by subtracting the VASI scores off from the SAVASI scores. RESULTS: A high correlation between the VASI and the SAVASI (ICC 0.97, 95% CI: 0.95-0.98) was found in 60 patients. The intra-rater reliability of the SAVASI (ICC 0.75, 95% CI 0.54-0.87) was adequate in 31 patients. Fifty (83%) of the patients completed the questionnaire within 10 min and only five (8%) of the patients considered the SAVASI hard. We found no correlation between overestimation of the SAVASI score and the Skindex-29 score. CONCLUSION: The SAVASI is a valid, reliable and acceptable self-assessment tool to measure the degree of depigmentation in vitiligo. With the SAVASI the degree of depigmentation can reliably be assessed by the patient themselves which can be useful in large (epidemiological) studies. Furthermore, this could contribute to the patient's disease insight and therapy loyalty.
Subject(s)
Diagnostic Self Evaluation , Quality of Life , Surveys and Questionnaires , Vitiligo/pathology , Adult , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care , Reproducibility of Results , Severity of Illness Index , Time Factors , Young AdultABSTRACT
This article summarizes the contributions in this special issue on Diffraction-Limited Storage Rings. It analyses the progress in accelerator technology enabling a significant increase in brightness and coherent fraction of the X-ray light provided by storage rings. With MAX IV and Sirius there are two facilities under construction that already exploit these advantages. Several other projects are in the design stage and these will probably enhance the performance further. To translate the progress in light source quality into new science requires similar progress in aspects such as optics, beamline technology, detectors and data analysis. The quality of new science will be limited by the weakest component in this value chain. Breakthroughs can be expected in high-resolution imaging, microscopy and spectroscopy. These techniques are relevant for many fields of science; for example, for the fundamental understanding of the properties of correlated electron materials, the development and characterization of materials for data and energy storage, environmental applications and bio-medicine.
Subject(s)
Equipment Design/trends , Image Enhancement/instrumentation , Optics and Photonics/trends , Synchrotrons/instrumentation , X-Ray Diffraction/instrumentation , X-Ray Diffraction/trendsABSTRACT
Fresnel zone plates (FZPs) play an essential role in high spatial resolution x-ray imaging and analysis of materials in many fields. These diffractive lenses are commonly made by serial writing techniques such as electron beam or focused ion beam lithography. Here we show that pinhole diffraction holography has potential to generate FZP patterns that are free from aberrations and imperfections that may be present in alternative fabrication techniques. In this presented method, FZPs are fabricated by recording interference pattern of a spherical wave generated by diffraction through a pinhole, illuminated with coherent plane wave at extreme ultraviolet (EUV) wavelength. Fundamental and practical issues involved in formation and recording of the interference pattern are considered. It is found that resolution of the produced FZP is directly related to the diameter of the pinhole used and the pinhole size cannot be made arbitrarily small as the transmission of EUV or x-ray light through small pinholes diminishes due to poor refractive index contrast found between materials in these spectral ranges. We also find that the practical restrictions on exposure time due to the light intensity available from current sources directly imposes a limit on the number of zones that can be printed with this method. Therefore a trade-off between the resolution and the FZP diameter exists. Overall, we find that this method can be used to fabricate aberration free FZPs down to a resolution of about 10 nm.
Subject(s)
Holography/instrumentation , Lasers , Nanopores/ultrastructure , Refractometry/instrumentation , Equipment Design , Equipment Failure AnalysisABSTRACT
Extension of neurites from a cell body is essential to form a functional nervous system; however, the mechanisms underlying neuritogenesis are poorly understood. Ena/VASP proteins regulate actin dynamics and modulate elaboration of cellular protrusions. We recently reported that cortical axon-tract formation is lost in Ena/VASP-null mice and Ena/VASP-null cortical neurons lack filopodia and fail to elaborate neurites. Here, we report that neuritogenesis in Ena/VASP-null neurons can be rescued by restoring filopodia formation through ectopic expression of the actin nucleating protein mDia2. Conversely, wild-type neurons in which filopodia formation is blocked fail to elaborate neurites. We also report that laminin, which promotes the formation of filopodia-like actin-rich protrusions, rescues neuritogenesis in Ena/VASP-deficient neurons. Therefore, filopodia formation is a key prerequisite for neuritogenesis in cortical neurons. Neurite initiation also requires microtubule extension into filopodia, suggesting that interactions between actin-filament bundles and dynamic microtubules within filopodia are crucial for neuritogenesis.
Subject(s)
Cerebral Cortex/cytology , Neurites/physiology , Neurons/physiology , Pseudopodia/physiology , Actins/metabolism , Animals , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/physiology , Cells, Cultured , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Laminin/physiology , Mice , Mice, Knockout , Microfilament Proteins/genetics , Microfilament Proteins/physiology , Microtubule-Associated Proteins , Microtubules/physiology , Mutation , Myosin Type II/antagonists & inhibitors , Myosins/biosynthesis , NADPH Dehydrogenase/biosynthesis , Neurons/ultrastructure , Phosphoproteins/genetics , Phosphoproteins/physiologySubject(s)
Melanocytes/drug effects , Occupational Diseases/immunology , Phenols/toxicity , T-Lymphocytes/immunology , Vitiligo/immunology , Apoptosis/drug effects , Apoptosis/immunology , Cells, Cultured , Humans , Male , Melanins/biosynthesis , Melanocytes/immunology , Melanocytes/metabolism , Middle Aged , Occupational Diseases/chemically induced , Occupational Exposure/adverse effects , Oxidative Stress/drug effects , Oxidative Stress/immunology , Primary Cell Culture , Skin/cytology , Skin/immunology , Skin/pathology , Skin Pigmentation/drug effects , Skin Pigmentation/immunology , Vitiligo/chemically induced , Vitiligo/pathologyABSTRACT
Major surgery in persons with haemophilia A and inhibitors is increasingly being performed. Both recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (APCC) are used to cover surgery but it remains unclear what the optimal dosing schedules are. We describe the use of a hybrid regimen in four inhibitor patients undergoing eight major surgical procedures using rFVIIa in the initial 2-6 postoperative days followed by FEIBA for the remaining period. All patients were also treated with tranexamic acid while receiving rFVIIa. We performed six major orthopaedic procedures, one emergency orchidectomy and one open appendectomy. The dosing schedules were at the higher end of those described in the literature but within the recommendations of the summary of product characteristics. Despite this, we encountered non-surgical bleeding in four of eight episodes. Three of these occurred in one individual suggesting a patient factor. The overall outcome was good for all episodes. The hybrid regimen combines flexibility of dose and dosing frequency of rFVIIa in the immediate postoperative setting with the advantage of a reduced dosing frequency with FEIBA in the subsequent days. This study also emphasizes that surgical procedures in this patient group remain a challenge.
Subject(s)
Antibodies, Neutralizing/immunology , Blood Coagulation Factors/immunology , Blood Coagulation Factors/therapeutic use , Factor VIIa/immunology , Factor VIIa/therapeutic use , Hemophilia A/drug therapy , Hemophilia A/surgery , Adult , Appendectomy , Drug Therapy, Combination , Hemophilia A/immunology , Humans , Male , Middle Aged , Orchiectomy , Postoperative Period , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic useABSTRACT
BACKGROUND: Severe asthma (SA) presents a considerable healthcare challenge despite optimal standard treatment. Dupilumab, which is effective in type 2 (T2) SA patients, demonstrates variable responses, categorizing patients as non-responders, partial responders, or those achieving clinical remission. However, real-world response rates remain underexplored. Additionally, understanding the characteristics of patients achieving clinical remission is crucial for predicting favourable responses to dupilumab. OBJECTIVE: To investigate responder types and identify predictors of clinical remission and non-response induced by dupilumab in a real-world cohort of SA patients. METHODS: We analyzed retrospective data from SA patients undergoing dupilumab treatment in a study conducted at Franciscus Gasthuis & Vlietland hospital. Data were collected at baseline and at a 12 to 24-months follow-up (T = 12). Response rates were evaluated at T = 12. Predictors of non-response and clinical remission were investigated using multivariate logistic regression analysis with a stepwise forward variable selection approach. RESULTS: Among the 175 patients screened, 136 met the inclusion criteria. At T = 12, 31.6 % achieved clinical remission, 47.1 % were partial responders and 21.3 % were non-responders. Predictors associated with clinical remission included high baseline blood eosinophil counts (BEC) and male sex. Conversely, younger age at baseline, low baseline total immunoglobin E (IgE) and low baseline fractional exhaled nitric oxide (FeNO) levels were identified as predictors of non-response. CONCLUSIONS: Dupilumab results in clinical disease remission in one-third of the treated patients. Clinical remission is predicted by high BEC and male sex, whereas low total IgE, low FeNO and younger age indicate a lower likelihood of response.
Subject(s)
Antibodies, Monoclonal, Humanized , Asthma , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Asthma/physiopathology , Male , Female , Middle Aged , Retrospective Studies , Adult , Treatment Outcome , Severity of Illness Index , Remission Induction , Aged , Cohort Studies , Anti-Asthmatic Agents/therapeutic use , Eosinophils , Immunoglobulin E/bloodABSTRACT
BACKGROUND: In vitiligo, many provoking factors have been described, but epidemiological data, especially on the role of contact with chemicals, are scarce. OBJECTIVE: To obtain an insight into the patient-reported factors provoking vitiligo, including contact with chemicals. METHODS: A retrospective cohort study was conducted on all 1264 patients with vitiligo who visited the Netherlands Institute for Pigment disorders from January 2003 to December 2007. Patients for whom an exogenous provoking factor was recorded were sent a questionnaire. Subsequently, patients who mentioned a chemical provoking factor were contacted to elucidate the alleged causal relationship between exposure to the chemical and the onset of vitiligo. RESULTS: A total of 300 out of the 1264 patients indicated that provoking factors had played a role in their disease. Two hundred and forty-six patients were sent a questionnaire, which was returned by 177 (response rate of 72%). Emotional stress was indicated as a provoking factor in 98 patients (55.4%), 51 patients (28.8%) recorded sunburn, 34 patients (19.2%) recorded mechanical factors and 20 patients (11.3%) other factors. Of 29 patients (16.4%) who indicated a chemical factor, a presumed causal relationship could be corroborated in four. The chemicals involved were para-tertiary butylphenol (n = 2), captan (n = 1) and diphencyprone (n = 1). CONCLUSION: The majority of the patients with vitiligo from this study did not mention provoking factors, but the ones who did point to emotional stress in more than half of the cases. Of the 29 patients who assigned chemical provoking factors, solvents were mainly indicated. However, a presumed relationship with the chemical could be corroborated in only four patients.
Subject(s)
Captan/adverse effects , Cyclopropanes/adverse effects , Phenols/adverse effects , Solvents/adverse effects , Stress, Psychological/complications , Vitiligo/chemically induced , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Sunburn/complications , Sunlight/adverse effects , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: In widespread vitiligo, when repigmentation therapies are no longer feasible, Q-switched lasers can be used to remove the remaining disfiguring pigmentation. However, little literature is available on the long-term effects of Q-switched laser treatment in patients with vitiligo, and the variables influencing the effect of treatment are unknown. OBJECTIVE: To evaluate retrospectively the effectiveness, safety and patient satisfaction of Q-switched ruby (QSR) laser-induced depigmentation in widespread vitiligo. METHODS: We performed a retrospective study on well-documented patients with vitiligo with widespread lesions who received depigmentation therapy with the QSR laser between 2000 and 2012 in our institute. Eligible patients were asked to visit our institute for assessment of depigmentation and to fill in a questionnaire on patient satisfaction and disease variables. RESULTS: After a mean follow-up of 13 months, 48% of the 27 included patients showed > 75% depigmentation. Patients with active disease at the time of treatment had significantly better results than patients with stable disease (P < 0·05). Twenty-three (85%) patients were satisfied after treatment. Eighteen patients (67%) reported temporary side-effects after treatment. None of the patients reported adverse effects, such as scars or infections. CONCLUSION: Q-switched ruby laser therapy is effective in approximately half of patients treated; it is a safe treatment with a high patient satisfaction. Patients with active vitiligo show better results after treatment than patients with stable vitiligo. Therefore, in patients with stable vitiligo resistant to trial treatment, we advise postponing treatment until their vitiligo becomes active.