Usability and feasibility of E-nergEYEze: a blended vision-specific E-health based cognitive behavioral therapy and self-management intervention to reduce fatigue in adults with visual impairment.

BACKGROUND: Over 50% of adults with visual impairment experience severe fatigue. Therefore, we developed a guided E-health intervention based on cognitive behavioral therapy and self-management to reduce fatigue in this population. This pilot study evaluated the usability, feasibility, fidelity and potential effectiveness of E-nergEYEze. METHODS: E-nergEYEze was developed by a design team and customized by conducting a pilot study using an iterative development strategy. The intervention was first tested in a usability study among adults with visual impairment (n = 5). Participants were asked to think-aloud while exploring the intervention features and a semi-structured interview was performed afterwards. Subsequently, the enhanced intervention was tested in a feasibility study. Adults with visual impairment and severe fatigue (n = 10) followed the intervention partially with guidance from a social worker and one-time computer trainer support. Fatigue severity (Checklist Individual Strength), fatigue impact (Modified Fatigue Impact Scale) and cognitive behavioral therapy skills (Competencies of Cognitive Therapy Scale-Self Report) were measured at baseline and at three months follow-up and analyzed with the Wilcoxon signed-rank test. The intervention was evaluated through evaluation forms. RESULTS: The usability study resulted in adjustments to content and lay-out with regard to optically shortened text sentences, separate pages for information and assignments with one read-aloud audio and an additional descriptive explanation of page content. Digital challenges were overcome with mandatory computer training and e-platform modifications. The feasibility study showed a positive trend in reducing fatigue severity (Z -6.108; P < .001; SD 8.4), impact of fatigue (Z - 4.451; P < .001; SD 11.4) and cognitive behavioral therapy skills (Z -2.278; P = .023; SD 19.3). Participants gave useful feedback regarding accessibility, content and guidance, with an overall positive experience. The intervention was rated with a median score of 8 (range 7-10). CONCLUSION: We developed, evaluated and optimized E-nergEYEze by applying a user-centered and iterative approach. E-nergEYEze showed a promising trend to reduce fatigue severity and impact of fatigue and to increase cognitive behavioral therapy skills. The study methods were feasible and the fidelity of the intervention protocol was suitable. Performing a randomized controlled trial is warranted to give insight into whether E-nergEYEze is cost-effective in reducing severe fatigue in adults with visual impairment. TRIAL REGISTRATION: International Clinical Trial Registry Platform: NL7764. Date registered: 28-05-2019.

Preliminary Study on Open Labelled Randomized Controlled Trial of the Safety and Efficacy of Hydroxychloroquine and Chloroquine Phosphate for the Treatment of Persons Infected with 2019 Coronavirus Disease in Nigeria.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 is a leading cause of ill-health and deaths worldwide. Currently, COVID-19 has no known widely approved therapeutics. Thus, the need for effective treatment. OBJECTIVES: We investigated the safety and efficacy of two (2) therapeutic agents; chloroquine phosphate (CQ), 2- hydroxychloroquine (HCQ) and a control (standard supportive therapy) among hospitalized adults with COVID-19. METHODS: The clinical trial was done in accordance to the World Health Organization master protocol for investigational therapeutics for COVID-19. Atotal of 40 participants with laboratory-confirmed positive COVID-19 were enrolled. Blood samples and oropharyngeal (OP) swabs were obtained on days 1,3,15 and 29 for safety and efficacy assessments. RESULTS: The baseline demographics showed that the median ages in years (range) were 45 (31-57) in CQ, 45 (36.5-60.5) in HCQ, 43 (39.5-67.0) and 44.5 (25.3-51.3) in the control (P<0.042).At randomization, seven (7) participants were asymptomatic, thirty-three (33) had mild symptoms, eight (8) had moderate symptoms while three (3) had severe symptoms. The average day of conversion to negative COVID-19 was 15.5 days for CQ, 16 days for HCQ and 18 days for the control(P=0.036). CONCLUSION: The safety assessment revealed no adverse effect of the drugs in COVID-19 patients after treatment. These findings proved that chloroquine and hydroxychloroquine are effective for the treatment of COVID-19 among hospitalized adults. It also confirmed that they are safe.

CONTEXTE: Le coronavirus du syndrome respiratoire aigu sévère 2 (SARS-CoV-2),agentcausaldelaCOVID-19, est l'unedes principales causes demaladie et de décès dans le monde. À l'heure actuelle, il n'existe aucun traitement largement approuvé pour la COVID-19. Ainsi, ilya un besoin de traitement efficace. OBJECTIFS: Nous avons étudié l'innocuité et l'efficacité de deux (2) agents thérapeutiques, le phosphate de chloroquine (CQ) et l'hydroxychloroquine (HCQ), ainsi qu'un groupe témoin (traitement de soutien standard) chez des adultes hospitalisés atteints de la COVID-19.MÉTHODES: L'essai clinique a été mené conformément au protocole maître de l'Organisation mondiale de la santé pour les thérapeutiques à l'étude de la COVID-19. Au total, 40 participants atteints de la COVID-19, confirmée en laboratoire, ont été in scrits. Des échantillons de sang et des prélèvements oropharyngés (PO) ont été effectuésauxjours1,3,15et29pourévaluerl'innocuitéetl'efficacité. RÉSULTATS: Les données démographiques initiales ont révélé que l'âge médian en années (plage) était de 45 (31-57) pour le groupe CQ, de 45 (36,5-60,5) pour le groupe HCQ, de 43 (39,5-67,0) et de 44,5 (25,3-51,3) pour le groupe témoin (P<0,042). À la randomisation, sept (7) participants étaient asymptomatiques, trente-trois (33) présentaient des symptômes bénins, huit(8) avaient des symptômes modérés, tandis que trois(3) avaient des symptômes graves. Le jour moyende conversionentest COVID-19 négatif était de 15,5 jours pour le groupe CQ, de 16 jours pour le groupe HCQ et de 18 jours pourle groupe témoin (P=0,036). CONCLUSION: L'évaluation de la sécurité n'a révélé aucun effet indésirable des médicaments chez les patients atteints de la COVID-19 après le traitement. Ces conclusions ont prouvé que la chloroquine et l'hydroxychloroquine sont efficaces pour le traitement de la COVID-19 chez les adultes hospitalisés. Cela a également confirmé qu' ilssont sûrs. Mots-clés: COVID-19, SARS-CoV-2, essai clinique, innocuité, efficacité, thérapeutiques.

Clinical predictors of Covid-19 mortality in a tertiary hospital in Lagos, Nigeria: A retrospective cohort study.

Background: The predictors of mortality among patients presenting with severe to critical disease in Nigeria are presently unknown. Aim: The aim of this study was to identify the predictors of mortality among patients with COVID-19 presenting for admission in a tertiary referral hospital in Lagos, Nigeria. Patients and Methods: The study was a retrospective study. Patients' sociodemographics, clinical characteristics, comorbidities, complications, treatment outcomes, and hospital duration were documented. Pearson's Chi-square, Fischer's Exact test, or Student's t-test were used to assess the relationship between the variables and mortality. To compare the survival experience across medical comorbidities, Kaplan Meir plots and life tables were used. Univariable and multivariable Cox-proportional hazard analyses were conducted. Results: A total of 734 patients were recruited. Participants' age ranged from five months to 92 years, with a mean ± SD of 47.4 ± 17.2 years, and a male preponderance (58.5% vs. 41.5%). The mortality rate was 9.07 per thousand person-days. About 73.9% (n = 51/69) of the deceased had one or more co-morbidities, compared to 41.6% (252/606) of those discharged. Patients who were older than 50 years, with diabetes mellitus, hypertension, chronic renal illness, and cancer had a statistically significant relationship with mortality. Conclusion: These findings call for a more comprehensive approach to the control of non-communicable diseases, the allocation of sufficient resources for ICU care during outbreaks, an improvement in the quality of health care available to Nigerians, and further research into the relationship between obesity and COVID-19 in Nigerians.

Pro- and anti-inflammatory macrophages express a sub-type specific purinergic receptor profile.

Extracellular nucleotides act as danger signals that orchestrate inflammation by purinergic receptor activation. The expression pattern of different purinergic receptors may correlate with a pro- or anti-inflammatory phenotype. Macrophages function as pro-inflammatory M1 macrophages (M1) or anti-inflammatory M2 macrophages (M2). The present study found that murine bone marrow-derived macrophages express a unique purinergic receptor profile during in vitro polarization. As assessed by real-time polymerase chain reaction (PCR), Gαs-coupled P1 receptors A2A and A2B are upregulated in M1 and M2 compared to M0, but A2A 15 times higher in M1. The ionotropic P2 receptor P2X5 is selectively upregulated in M1- and M2-polarized macrophages. P2X7 is temporarily expressed in M1 macrophages. Metabotropic P2Y receptors showed a distinct expression profile in M1 and M2-polarized macrophages: Gαq coupled P2Y1 and P2Y6 are exclusively upregulated in M2, whereas Gαi P2Y13 and P2Y14 are overexpressed in M1. This consequently leads to functional differences between M1 and M2 in response to adenosine di-phosphate stimulation (ADP): In contrast to M1, M2 showed increased cytoplasmatic calcium after ADP stimulation. In the present study we show that bone marrow-derived macrophages express a unique repertoire of purinergic receptors. We show for the first time that the repertoire of purinergic receptors is highly flexible and quickly adapts upon pro- and anti-inflammatory macrophage differentiation with functional consequences to nucleotide stimulation.

Development and practice of laparoscopic surgery in a Nigerian tertiary hospital.

BACKGROUND: For the benefits of less postoperative pain, early recovery and discharge, and better cosmesis, laparoscopic surgery is rapidly gaining acceptance amongst surgeons as a better alternative to traditional open procedures. In January 2015, bookings for laparoscopic surgery became a more regular feature on our operation list. AIMS: We reported the indications, management outcome, and challenges in patients who had laparoscopic surgery in our institution. This is to document the trends in our surgical practice. METHODOLOGY: This is a descriptive study of 137 patients who had laparoscopic surgery for general surgical indications in our institution over a period of 5 years. Patients data as collected from the records department were evaluated for demographic characteristics, medical comorbidities, type of procedures done, and perioperative outcome. Data analysis was performed using Statistical Package for Social Sciences (SPSS). RESULTS: A total of 137 Patients had laparoscopic general surgery between January 2015 and December 2019. There were 48 males and 89 females with a male-to-female ratio of 1:1.9. The mean age of the patients was 38.8 ± 3.4 years (range 16-87 years). Laparoscopic cholecystectomy (35%) and laparoscopic appendicectomy (29.9%) were the most common procedures performed. Five (3.7%) cases were converted to open surgery. Superficial surgical site infection (5.8%) following laparoscopic appendicectomy was the most common postoperative complication. There was no 30-day postoperative mortality. CONCLUSION: Laparoscopic surgery is safe and can be applied to wide variety of general surgical conditions in developing countries. Minimal postoperative morbidity of laparoscopy is a major benefit to the patients.

IgG4-related disease in patients with newly diagnosed idiopathic retroperitoneal fibrosis: a population-based Danish study.

Objectives: IgG4-related disease (IgG4-RD) may present as 'idiopathic' retroperitoneal fibrosis (IRPF). We aimed to determine the occurrence of IgG4-retroperitoneal fibrosis (IgG4-RPF) in a nationwide study on patients with newly diagnosed IRPF, and to compare histopathological, imaging, and clinical features in the IgG4-RPF and non-IgG4-RPF subsets. Method: The National Danish Pathology Register was searched for biopsy codes relating to retroperitoneal tissue from 1 January 2004 to 31 December 2013. Secondary causes of RPF were excluded. Among 724 candidate cases, 68 were identified with IRPF. Clinical, laboratory, and imaging recordings were reviewed, and tissue blocks were scrutinized for IgG4-RPF features according to international consensus. Results: Forty-two patients (28 males), median age 56 (25-74) years were included. Nineteen (45%) met the criteria for IgG4-RPF, seven with definite and 12 with possible IgG4-RPF, while 23 had non-IgG4-RPF. Local manifestations and laboratory measures did not differ between RPF subsets. Arterial hypertension (p = 0.037) and periaortic fibrosis (p = 0.024) were more common in IgG4-RPF vs non-IgG4-RPF. Plasma cell IgG4/total IgG ratios ≥ 40% were associated more with core histopathological features of IgG4-RD compared to ratios < 40% (p < 0.001). There was a positive correlation between tissue IgG4-positive plasma cells and eosinophil cell count in patients with IgG4-RPF (rho = 0.50, p = 0.043). Conclusion: Forty-five per cent of this nationwide study population with newly diagnosed IRPF could be reclassified with IgG4-RPF. The association between high numbers of IgG4-bearing plasma cells and histopathological features of IgG4-RPF supports IgG4-bearing plasma cells with a perturbed distribution between IgG4 and total IgG being implicated in the pathogenesis of IgG4-RPF.

Treatment of a broncho-esophageal fistula complicated by severe ARDS.

INTRODUCTION: Broncho-esophageal fistula formation is a rare complication of tuberculosis, most often seen in immunocompromised patients. METHODS AND RESULTS: In this paper, we report the case of a young non-immunocompromised refugee from Somalia diagnosed with open pulmonary tuberculosis complicated by extensive osseous involvement and a broncho-esophageal fistula with consecutive aspiration of gastric contents. The patient rapidly developed a severe acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (ECMO) therapy for nearly 2 months. The fistula was initially treated by standard antituberculous combination therapy and implantation of an esophageal and a bronchial stent. Long-term antibiotic treatment was instituted for pneumonia and mediastinitis. 7 months later, discontinuity resection of the esophagus was performed and the bronchial fistula covered by an intercostal muscle flap. DISCUSSION: This case illustrates that tuberculosis should always be suspected in patients from high-incidence countries in case of lung involvement and that an interdisciplinary approach including long-term intensive care management can enable successful treatment of tuberculosis with severe, near-fatal complications.

[New aspects of thrombolysis and thrombectomy in pulmonary embolism]. / Neues zu Thrombolyse und Thrombektomie bei Lungenembolie.

Pulmonary embolism is a potentially life-threatening disease, which can present with varying severity. Based on an emergency risk stratification, the initial treatment strategy should be chosen without delay. While patients with a low mortality risk can be treated in an outpatient setting, patients at high risk should proceed to immediate recanalization by thrombolysis or thrombectomy. Systemic thrombolysis is the first line therapy in the absence of contraindications. The dosing (low versus full dose) and application (systemic versus local via a catheter) of alteplase, the most frequently used agent, is the subject of a number of current studies with the goal to reduce the risk of bleeding. In the case of contraindications for systemic thrombolysis surgical or alternatively, interventional thrombectomy should be performed. This article discusses these procedures in the light of the currently available literature.

[Transcatheter aortic valve implantation and internal carotid artery stenting in a 74-year-old female patient]. / Transkutaner Aortenklappenersatz kombiniert mit Stenting der A. carotis interna bei einer 74-jährigen Patientin.

This article presents the case of a combined intervention for transcatheter aortic valve implantation (TAVI) and stenting of the internal carotid artery. Due to severe aortic stenosis and a subacute infarction in the middle cerebral artery territory, with neurological instability while hypotensive and cardiac failure while hypertensive, it was decided to carry out the intervention as a single combined procedure. An open surgical intervention was decided against because of the high peri-interventional mortality risk. The intervention was complication-free but a slight subarachnoid hemorrhage occurred in the postinterventional period. It was unclear if the bleeding was the result of cerebral hyperperfusion poststenting, if bleeding in an ischemic region was favored by post-TAVI hyperemia and whether the outcome would have been better with two separate interventions.

Routine hemoglobin electrophoresis for pediatric surgery day case in at-risk populations: Suggested algorithm for screening using clinical risk factors.

BACKGROUND: Hemoglobin electrophoresis (HBE) is a part of the preoperative routine requested by anesthetists. However, the prevalence of hemoglobinopathy in the population is low. This study aims to determine the clinical risk factors for hemoglobinopathies and propose clinical guidelines for preoperative screening of patients for pediatric day care surgery. PATIENTS AND METHODS: A prospective study carried out over 12 months. Consecutive patients aged 6 months and older who had day case surgery were recruited to the study. Biodata and relevant clinical data were collated and documented in a proforma and analyzed using a statistical package for social sciences version 17. RESULTS: There were 124 patients106 boys and 18 girls. The median age was 3 years. Scrotal lesions were the most common conditions managed (71.7%). Seventy-eight percent of patients had HbAA, 15.3% had HbAS, and 4.8% had HbAC while 0.8% each had both HbSC and HbSS. At least one parent of 78.2% knew their Hb phenotype, of which, 79% were HbAA. A history of jaundice (P = 0.0001), hand and foot syndrome (P = 0.0001), frontal bossing (P = 0.0001), and low packed cell volume at surgery (P = 0.001) were found significant in predicting hemoglobinopathies. There was no mortality. CONCLUSION: Risk factors for hemoglobinopathies from this study included a positive history of jaundice, hand and foot syndrome, frontal bossing, and anemia. Proposed guidelines for HBE screening include the presence of hemoglobinopathy in one parent if one parent has sickle cell trait, and the other parent's genotype is unknown or if any of the risk factors is present.

[Pediatric emergence agitation]. / Postoperative Agitation im Kindesalter.

BACKGROUND: The origin of emergence agitation in children remains unclear; however, an association between surgical procedure, patient age and anesthetic regimen and the incidence of postoperative agitation has been described in the literature. AIM: The aim of this survey performed between February and April 2014 was to collect data from the daily clinical practice by experienced pediatric anesthesiologists regarding documentation, premedication, anesthesia regimen and postoperative treatment with respect to children with emergence agitation. MATERIAL AND METHODS: An online questionnaire with 33 items was developed and sent to all 525 members of the scientific committee of pediatric anesthesia (WAKKA) of the German Society of Anesthesiology and Intensive Care (DGAI). Members were asked to respond within a time period of 1 month but no reminders were sent out via email or telephone. RESULTS: A total of 156 members participated in the survey and of these 143 questionnaires were fully completed and included in the final evaluation (27 %). Of the participants 77 % had more than 6 years professional experience in the field of pediatric anesthesia and for 87 % emergence agitation remains a relevant clinical problem. The estimated incidence of emergence agitation was given as 1-10 % and as high as 11-20 % by 56% and 20 % of the participants, respectively. The incidence of postoperative agitation is documented by only 11 % of the participants with a validated score, such as the pediatric anesthesia emergence delirium (PEAD) scale and 89 % of the participants use midazolam for premedication. As a preemptive intervention total intravenous anesthesia is performed by 56 % whereas clonidine is used as first line prevention by 30 %. Postoperative pharmacological treatment is performed by a bolus administration of propofol (56 %) and clonidine (26 %). Postoperative parental presence was considered beneficial by 82 %. CONCLUSION: Emergence agitation is still seen as a relevant clinical problem by experienced pediatric anesthesiologists. Propofol is first choice when it comes to pharmacological prevention and treatment of emergence agitation. Postoperative parental presence was considered beneficial by the majority of anesthesiologists.

[Antiplatelet therapy after acute coronary syndrome. Therapeutic strategies and treatment duration]. / Antithrombozytäre Therapie nach akutem Koronarsyndrom. Differenzialtherapie und Dauer.

Besides percutaneous coronary interventions, antiplatelet drugs are of overwhelming importance for patients with acute coronary syndrome (ACS). For ACS patients, the guidelines recommend treatment with acetylsalicylic acid and a P2Y12 receptor antagonist. The third generation P2Y12 receptor antagonists prasugrel and ticagrelor provide stronger platelet inhibition than clopidogrel and improve the clinical outcome in patients with ACS; however, it is still under discussion which P2Y12 antagonist fits best to which subgroup of ACS patients. This article summarizes current guidelines and antiplatelet treatment strategies for patients with non-ST-segment elevation (NSTE) ACS or ST-segment elevation myocardial infarction (STEMI). The information is mainly based on the recently published guidelines of the European Society of Cardiology on myocardial revascularization.

Hypertensive heart disease: MR tissue phase mapping reveals altered left ventricular rotation and regional myocardial long-axis velocities.

OBJECTIVES: The aim of this study was the evaluation of left ventricular (LV) segmental 3D velocities in patients with hypertensive heart disease using magnetic resonance (MR) tissue phase mapping (TPM). METHODS: LV radial, long-axis and rotational myocardial velocities were assessed by TPM in patients with LV hypertrophy and preserved EF (n = 18, age = 53 ± 12 years) and volunteers (n = 20, age = 51 ± 4 years). Systolic and diastolic peak and time-to-peak velocities were mapped onto a 16-segment LV model. 3D myocardial motion was displayed on an extended visualisation model. Correlation coefficients were calculated to investigate differences in regional dynamics. RESULTS: Patients revealed diastolic dysfunction as expressed by decreased peak long-axis velocities in all (except apical) segments (basal, P ≤ 0.01; two midventricular segments, P = 0.02, P = 0.03). During systole, hypertrophy was associated with heterogeneous behaviour for long-axis velocities including an increase in anteroseptal apical and midventricular regions (P = 0.001), a reduction in mid-inferior segments (P = 0.03) and enhanced septal velocities (P < 0.05). Segmental correlation analysis revealed altered dynamics of LV base rotation and increased dyssynchrony of lateral long-axis motion. CONCLUSIONS: Patients with hypertensive heart disease demonstrated alterations in systolic long-axis motion, basal rotation and dyssynchrony. Longitudinal studies are needed to investigate the value of regional wall motion abnormalities regarding disease progression and outcome.

H-type tracheo-oesophageal fistula: a diagnostic challenge in a resource-poor country. A case report.

H-type fistula is a rare form of congenital tracheo-oesophageal fistula accounting for 4% of all cases of Tracheo-oesophageal fistula. The typical picture is that of recurrent chest infection due to both missed and delayed diagnosis as well as cyanosis and choking during feeds. In resource poor countries this problem is further exaggerated by ignorance, poverty and lack of access to basic investigative modalities. This is the case of [abstract incomplete].

The effectiveness of motivational interviewing on adherence to wearing orthopedic shoes in people with diabetes at low-to-high risk of foot ulceration: A multicenter cluster-randomized controlled trial.

AIM: To evaluate the effectiveness of motivational interviewing (MI) performed by MI-trained podiatrists in improving adherence to wearing orthopedic shoes in comparison to usual care in people with diabetes at low-to-high risk of ulceration. METHODS: People with diabetes with loss of protective sensation and/or peripheral artery disease, and with orthopedic shoes prescription were allocated to receive one MI-consultation by a podiatrist randomized to MI training (n = 53) or usual care only (n = 68). Adherence was measured as the percentage of steps taken while wearing orthopedic shoes, determined using an insole temperature microsensor and wrist-worn activity tracker during one week at 3 and 6 months. RESULTS: The proportion of participants ≥80 % adherent to wearing their orthopedic shoes was higher in the control group than in the MI-intervention group at 3 months (30.9 % versus 15.1 %; p = 0.044), and not significantly different at 6 months (22.1 % versus 13.2 %; p = 0.210). Average adherence was also higher in the control group than the intervention group at both 3 months (60.9 % versus 50.9 %; p = 0.029) and 6 months (59.9 % versus 49.5 %; p = 0.025). CONCLUSIONS: One podiatrist-led MI-consultation in its current form did not result in higher adherence to wearing orthopedic shoes in people with diabetes 3 and 6 months after inclusion. TRIAL REGISTRATION: Netherlands Trial Register NL7710 (available on the International Clinical Trials Registry Platform).

Expert evaluations of fatigue questionnaires used in rheumatoid arthritis: a Delphi study among patients, nurses and rheumatologists in the Netherlands.

OBJECTIVES: Evaluating fatigue items from traditional questionnaires and a new scale (BRAF-MDQ) by experts in rheumatoid arthritis (RA). This evaluation was part of a study to select fatigue items to develop an item bank for a Dutch computer-adaptive test (CAT) for RA. Experts' opinions were incorporated since they are essential for content validity of measurement instruments. METHODS: The 60 items of the SF-36 subscale vitality, FACIT-F, POMS subscale fatigue/inertia, MAF and the recently developed BRAF-MDQ were evaluated by rheumatologists, nurses and RA patients in a Delphi procedure. Items were selected for development of the item bank/CAT if rated as adequate by at least 80% of the participants (when 50% or less they were excluded). On the basis of participants' comments, remaining items were re-worded and re-evaluated in the following round. The procedure stopped when all items were selected or rejected. RESULTS: Ten rheumatologists, 20 nurses and 15 RA patients participated. After the first round, 40% of the traditional items and 60% of the BRAF-MDQ items were directly selected and 3 items of the traditional questionnaires and 1 item of the BRAF-MDQ were directly excluded. Remaining items were re-worded, eight of which were presented for re-evaluation in the second round. Finally, 90% of the items from the traditional questionnaires and 95% of the items from the new BRAF-MDQ were included in our item pool. CONCLUSIONS: Fifty-five of the 60 items (92%) from fatigue questionnaires proved to have good content validity and were feasible for use in the Netherlands, some after adaptation.

[Anticoagulation for atrial fibrillation : the future has begun]. / Antikoagulation bei Vorhofflimmern : Die Zukunft hat begonnen.

According to new criteria based on the CHAD(2)DS(2)-VASc score, the threshold for administering anticoagulation therapy for atrial fibrillation patients is being increasingly lowered. With the development of new anticoagulants, more therapy options are available. Currently, vitamin K antagonists are still the standard treatment. However, this therapy is problematic for some patients. Because of the increased bleeding risk and need for continuous blood tests to monitor coagulation, many patients needing anticoagulation therapy are not treated. The new anticoagulants apixaban, rivaroxaban and dabigatran were developed with the goal of avoiding these problems. Dabigatran has already been approved for thromboembolism prophylaxis for patients with atrial fibrillation. All three substances do not require routine control blood tests. Whether the costs saved by this together with the prevention of ischemic and bleeding events justify the higher price of these drugs compared to vitamin K antagonists needs to be examined by socioeconomic studies.

Ivermectin shows clinical benefits in mild to moderate COVID19: a randomized controlled double-blind, dose-response study in Lagos.

INTRODUCTION: In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS-CoV-2 viral replication, but questions remained as to in-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19. METHODS: We conducted a translational proof of concept randomized, double blind placebo controlled, dose response and parallel group study of IV efficacy in RT-polymerase chain reaction proven COVID 19 positive patients. Sixty-two patients were randomized to three treatment groups. (A) IV 6 mg regime, (B) IV 12 mg regime (given Q84 h for 2 weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care. RESULTS: The Days to COVID negativity (DTN) was significantly and dose dependently reduced by IV (P = 0.0066). The DTN for Control were, = 9.1+/-5.2, for A 6.0 +/- 2.9 and for B 4.6 +/-3.2. Two way repeated measures ANOVA of ranked COVID 19 +/- scores at 0, 84, 168 and252h showed a significant IV treatment effect (P = 0.035) and time effect (P < 0.0001). IV also tended to increase SPO2% compared to controls, P = 0.073, 95% CI-0.39 to 2.59 and increased platelet count compared to C (P = 0.037) 95%CI 5.55-162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = -0.52, P = 0.005). No SAE was reported. CONCLUSIONS: 12mg IV regime given twice a week may have superior efficacy over 6mg IV given twice a week, and certainly over the non IV arm of the study. IV should be considered for use in clinical management of SARS-COV2, and may find applications in prophylaxis in high risk areas.

Attitudes and experiences towards the application of motivational interviewing by podiatrists working with people with diabetes at high-risk of developing foot ulcers: a mixed-methods study.

BACKGROUND: Podiatrists are key professionals in promoting adequate foot self-care for people with diabetes at high-risk of developing foot ulcers. However, merely informing patients about the advantages of foot self-care is insufficient to realise behavioural change. Motivational interviewing (MI) is a promising person-centred communication style that could help to create a working alliance between healthcare providers and patient to improve foot self-care. This study aims to observe and analyse the application of MI in consultations carried out by MI-trained and non-MI-trained podiatrists with their patients, and explore podiatrists' attitudes and experiences towards MI. METHODS: Eighteen podiatrists (median age: 28.5 years, 10 female and 8 male) followed a three-day basic training in MI and 4 podiatrists (median age: 38.5 years, 4 female) were not trained in MI. To observe and rate the MI-fidelity in daily clinical practice, audio recordings from the MI-trained and non-MI-trained podiatrists were scored with the Motivational Interviewing Treatment Integrity code. Individual, semi-structed, in-depth interviews were conducted with the MI-trained podiatrists to explore their attitudes towards and experiences with MI. These data sources were triangulated to describe the effect of training podiatrists in MI for their clinical practice. RESULTS: The MI-trained podiatrists scored significantly higher than the non-MI-trained podiatrists on two of four global MI-related communication skills (empathy, p = 0.008 and change talk, p = 0.008), on one of five core MI-adherent behaviours (affirmation, p = 0.041) and on one of the other behaviour counts (simple reflections, p = 0.008). The podiatrists mainly reported their attitudes and experiences regarding partnership and cultivating change talk, during the interviews. In addition, they also mentioned facilitators and barriers to using MI and indicated whether they experienced MI as having added value. CONCLUSIONS: The MI-trained podiatrists used the principles of MI at a solid beginner proficiency level in their clinical practice in comparison to the non-MI-trained podiatrists, who did not reach this level. This achievement is in accordance with the basic MI-training they received. This multi-method study reveals that podiatrists can be effectively trained in applying MI in daily clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL7710. Registered: 6 May 2019.

Opposing effects of monomeric and pentameric C-reactive protein on endothelial progenitor cells.

C-reactive protein (CRP) has been linked to the pathogenesis of atherosclerosis. The dissociation of native, pentameric (p)CRP to monomeric (m)CRP on the cell membrane of activated platelets has recently been demonstrated. The dissociation of pCRP to mCRP may explain local pro-inflammatory reactions at the site of developing atherosclerotic plaques. As a biomarker, pCRP predicts cardiovascular adverse events and so do reduced levels and function of circulating endothelial progenitor cells (EPCs). We hypothesised that mCRP and pCRP exert a differential effect on EPC function and differentiation. EPCs were treated with mCRP or pCRP for 72 h, respectively. Phenotypical characterisation was done by flow cytometry and immunofluorescence microscopy, while the effect of mCRP and pCRP on gene expression was examined by whole-genome gene expression analysis. The functional capacity of EPCs was determined by colony forming unit (CFU) assay and endothelial tube formation assay. Double staining for acetylated LDL and ulex lectin significantly decreased in cells treated with pCRP. The length of tubuli in a matrigel assay with HUVECs decreased significantly in response to pCRP, but not to mCRP. The number of CFUs increased after pCRP treatment. RNA expression profiling demonstrated that mCRP and pCRP cause highly contradictory gene regulation. Interferon-responsive genes (IFI44L, IFI44, IFI27, IFI 6, MX1, OAS2) were among the highly up-regulated genes after mCRP, but not after pCRP treatment. In conclusion, EPC phenotype, genotype and function were differentially affected by mCRP and pCRP, strongly arguing for differential roles of these two CRP conformations. The up-regulation of interferon-inducible genes in response to mCRP may constitute a mechanism for the local regulation of EPC function.