If only they knew! A non-inferiority randomized controlled trial comparing deceptive and open-label placebo in healthy individuals.

BACKGROUND: Placebo use is widespread in clinical practice. However, they are most often administered deceptively rather than openly. It is often suggested that open-label placebos (OLP) are less effective than deceptive placebos (DP). This study aimed to compare the use of DP and OLP treatments to reduce pain in healthy volunteers. METHODS: We conducted a non-inferiority, parallel, randomized, controlled trial, which also included a nested cross-over no-treatment condition. This study was conducted at a university clinic in France. RESULTS: We included 60 subjects and the main result shows that the OLP was not inferior to the DP by a margin of 10 mm. The mean difference between both groups regarding intensity of pain was 0.7 mm with a 95% compatibility interval (95% CI) of ]-∞; 5.4], and 97.5% CI of ]-∞; 6.3]. Secondary outcomes require cautious interpretation of the effect of placebo versus no treatment due to a time-treatment interaction. CONCLUSION: The study indicates that OLP may perform just as well as DP and could provide support for the use of OLP as an ethical alternative to DP when they are to be used in a clinical setting. If only patients knew about the placebo nature of some treatments they are receiving, unnecessary lies could be avoided while maintaining similar placebo effects. SIGNIFICANCE: This study is the first to show non-inferiority of placebos administered honestly, also called OLP, compared to DP in reducing pain. This suggests that OLP could be as effective as their deceptive counterparts while having the ethical advantage of not being required to lie. If deception is not a necessary condition for efficacy, OLP should be preferred over DP.

Isolated distal deep vein thrombosis: What have we learnt from the OPTIMEV study?

The OPTIMEV (OPTimisation de l'Interrogatoire dans l'évaluation du risque throMbo-Embolique Veineux) study has provided some important and innovative information for the management of lower extremity isolated distal deep vein thrombosis (distal DVT). Indeed, if distal deep-vein thrombosis (DVT) therapeutic management is nowadays still debated, before the OPTIMEV study, the clinical relevance of these DVT itself was questioned. Via the publication of 6 articles, between 2009 and 2022, assessing risk factors, therapeutic management, and outcomes of 933 patients with distal DVT we were able to demonstrate that: - When distal deep veins are systematically screened for suspicion of DVT, distal DVT are the most frequent clinical presentation of the venous thromboembolic disease (VTE). This is also true in case of combined oral contraceptive related VTE. - Distal DVT share the same risk factors as proximal DVT and constitute two different clinical expressions of the same disease: the VTE disease. However, the weight of these risk factors differs: distal DVT are more often associated with transient risk factors whereas proximal DVT are more associated with permanent risk factors. - Deep calf vein and muscular DVT share the same risk factors, short and long-term prognoses. - In patients without history of cancer, risk of unknown cancer is similar in patients with a first distal or proximal DVT. - After 3years and once anticoagulation has been stopped, distal DVT recur twice less as proximal DVT and mainly as distal DVT; However, in cancer patients, prognosis of distal and proximal DVT appear similar in terms of death and VTE recurrence.

Exogenous copper exposure causing clinical wilson disease in a patient with copper deficiency.

BACKGROUND: Human Swayback is a disease characterized by acquired copper deficiency which primarily manifests as myeloneuropathy. Common causes include malabsorptive disorders, gastric surgery, total parenteral nutrition and excessive zinc intake. In contrast, copper supplementation should be closely monitored as excessive doses can lead to acute intoxication and in chronic cases, cirrhosis. Copper derangements are rare, however it is important to consider them due to potential severe complications. CASE PRESENTATION: We present a middle-aged man who had been previously diagnosed with Human Swayback after presenting with various neurological symptoms. The patient was subsequently placed on copper supplementation. A decade later, he was referred to our hospital for liver transplant evaluation due to new diagnosis of decompensated end-stage liver disease after an abdominal surgery. His initial workup was suggestive of Wilson disease-subsequent ATP7B gene was negative. Ultimately, the patient underwent liver transplantation; liver explant was significant for a copper dry weight concentration of 5436 mcg/g. CONCLUSIONS: Human Swayback is a very rare copper-related disease which deserves awareness due to its potential irreversible health effects in the human body. Additionally, in patients who require copper supplementation, serial levels should be monitored to ensure adequate copper levels.

Radiograph prescription practices of dentists in Ontario, Canada.

BACKGROUND: With the advent of new ionizing radiation technologies, consideration must be given to the use of radiography in clinical practice. The authors aimed to determine how general dentists obtain oral and maxillofacial images and whether dentists' demographic characteristics and practice environments affect imaging decisions. METHODS: The authors conducted a cross-sectional study using an electronic survey to collect information from general dentists in Ontario, Canada's most populous province. RESULTS: The authors received 1,332 responses from 9,052 general dentists registered to practice in Ontario. A total of 57.2% of dentists used a nonindividualized approach to obtaining images for new adult dentate patients. Using clinical case scenarios, the authors found that 18.8% through 55.1% of dentists did not follow evidence-based guidelines when obtaining images. Overprescribing imaging was 5.8 times more common than underprescribing. Seeing patients after images were obtained (odds ratio [OR], 5.5), owning a panoramic and a cone-beam computed tomography imaging system (OR, 4.4), and the belief that images should be obtained to screen for occult pathoses (OR, 3.5) were the factors most strongly associated with overprescription. CONCLUSIONS: Radiography prescription practices varied considerably among general dentists in Ontario and did not conform to established guidelines. Factors other than patient needs appeared to influence imaging practices. PRACTICAL IMPLICATIONS: Overprescription of imaging by general dentists can result in unnecessary radiation exposure and financial costs to patients. To mitigate this, changes are needed in dental education, continuing education courses, and regulatory requirements.

Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C.

Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. RESULTS: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. CONCLUSIONS: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

The use of radiographic imaging technologies by general dentists in Ontario, Canada.

OBJECTIVE: The aim of this study was to determine the prevalence of 2-dimensional and 3-dimensional digital imaging technologies, the methods used by general dentists to limit patient exposure to ionizing radiation, and the impact of dentists' education on imaging technologies and patient dose-reducing techniques. STUDY DESIGN: A cross-sectional, web-based survey of all general dentists in Ontario was conducted. RESULTS: Responses from 1332 (14.7%) of the 9052 registered general dentists in Ontario were included in the analysis. Approximately 89% reported using digital intraoral technology, 81.1% reported owning panoramic imaging systems, 71.2% reported making referrals for cone beam computed tomography (CBCT), and 9.5% reported including CBCT in their practices. CBCT was most commonly used for dental implant treatment planning (85.8%), followed by endodontics (45.4%), evaluation of pathology (39.6%), and surgical assessment for impacted teeth or difficult extractions (36.8%). Approximately 32.7% used only collimators with a long focal point-receptor distance and 8% used only rectangular collimation; 86.9% reported using a thyroid collar when imaging patients. Differences in educational backgrounds correlated with differences in the use of imaging and dose-reducing techniques. CONCLUSIONS: There is widespread adoption of digital imaging technologies by general dentists in Ontario, including CBCT. Greater implementation of long and/or rectangular collimation could markedly reduce the ionizing radiation dose to patients. Changes in dental education curricula and continuing education course offerings may address these issues.

Outcomes following liver transplantation from HCV-seropositive donors to HCV-seronegative recipients.

BACKGROUND & AIMS: Grafts from HCV-seropositive donors can now be considered for liver transplantation (LT) owing to the advent of direct-acting antivirals (DAAs). We report on our multicenter experience of transplanting liver grafts from HCV-seropositive donors into HCV-seronegative recipients. METHODS: This is a prospective multicenter observational study evaluating outcomes in adult HCV-seronegative LT recipients who received grafts from HCV-seropositive donors in 3 US centers. RESULTS: From 01/18 to 09/19, 34 HCV-seronegative LT recipients received grafts from HCV-seropositive donors (20 HCV-viremic and 14 non-viremic). Seven grafts were from cardiac-dead donors. The median MELD-Na score at allocation was 20. Six recipients underwent simultaneous liver-kidney transplant and 4 repeat LT. No recipient of an HCV-non-viremic graft developed HCV viremia. All 20 patients who received HCV-viremic grafts had HCV viremia confirmed within 3 days after LT. DAA treatment was started at a median of 27.5 days after LT. Median pre-treatment viral load was 723,000 IU/ml. All (20/20) patients completed treatment and achieved SVR12. Treatment was well tolerated with minimal adverse events. One patient developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease, despite achieving viral clearance. This patient died due to presumed infectious complications. A recipient of an HCV-non-viremic graft died with acute myocardial infarction 610 days post LT. CONCLUSIONS: Transplantation of liver grafts from HCV-seropositive donors into HCV-seronegative recipients resulted in excellent short-term outcomes. Antiviral therapy was effective and well tolerated. Careful ongoing assessment and prompt initiation of antiviral therapy are recommended. Longer term follow-up in carefully conducted clinical trials is still required to confirm these results. LAY SUMMARY: This study shows that livers from donors exposed to HCV expand the donor pool and can be used safely in patients who are seronegative for hepatitis C infection. Treatment, initiated early post transplantation, is effective and resulted in cure in all patients.

Hepatitis C Testing and Liver Fibrosis Predictors in the Birth Cohort of a Primary Care Practice.

OBJECTIVE: To determine the prevalence of and risk factors for advanced fibrosis in patients born from 1945 through 1965 (birth cohort) who underwent testing for hepatitis C virus (HCV). PATIENTS AND METHODS: Data were extracted from the electronic health record of all patients receiving primary care at a single academic institution who underwent HCV testing between September 8, 2010, and March 5, 2018. The birth cohort patients were the primary focus of the study. Fibrosis 4 (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) scores were calculated to screen for fibrosis. RESULTS: During the study period, 7097 birth cohort patients had HCV antibody testing, 3462 (48.8%) of whom were men, 6435 (91.0%) were white, 1028 (14.5%) had diabetes mellitus, 2,034 (36.5%) had an alanine aminotransferase (ALT) level greater than 30 U/L, and 2,396 (34.2%) had body mass index of 30 kg/m2 or greater. Hepatitis C virus antibody was present in 124 (1.7%), 33 (26.6%) of whom had HCV viremia. Estimated prevalence of METAVIR [Meta-analysis of Histological Data in Viral Hepatitis] stage 4 fibrosis was 4.1% (180 of 4433) by a FIB-4 score of 3.25 or greater and 4.3% (204 of 4763) by an APRI score greater than 1.0. The odds ratio (OR) for fibrosis, determined by APRI, was significant for HCV RNA positivity (OR, 15.98; 95% CI, 7.23-35.32; P<.001), diabetes mellitus (OR, 1.98; 95% CI, 1.40-2.79; P<.001), and ALT value greater than 30 U/L (OR, 15.07 U/L; 95% CI, 9.27-24.52 U/L; P<.001) but not for body mass index of 30 kg/m2 or greater (OR, 0.77; 95% CI, 0.56-1.06; P=.11). CONCLUSION: Hepatitis C virus viremia, diabetes mellitus, and elevated ALT levels were associated with increased odds for development of fibrosis. In addition to HCV testing, diabetes mellitus and elevated ALT level are potential parameters to use for recommending noninvasive testing for fibrosis.

Use of a smart electrically assisted bicycle (VELIS) in the health field -Proof of concept.

Physical activity (PA) is highly recommended in the management of most chronic diseases. For these patients, the smart electric bicycle can be effective to improve adherence to this behavior. The E-bike used in this study (called VELIS) has an innovative onboard technology that allows for subject monitoring and the engine power is designed to adapt to the user's abilities. A prerequisite for the use of the VELIS with patients is to initially carry out a pilot study on healthy subjects. The objective was to evaluate the impact of the customizable settings on physiological parameters and to ensure this prototype's efficiency and safety of use. Twelve healthy participants with various profiles (physical condition, used to cycling or not) were included. They have completed four times a 14 km itinerary with various settings of the VELIS. We recorded GPS data, heart rate and perceived exertion. Based on exercise intensity, we confirm that riding an E-bike should be considered as a physical activity. Safety of the participants is ensured by the engine brake. Recordings show that it took between 1 and 3 min for the novice to become familiar with the VELIS and to get optimal assistance. The main finding of this pilot study confirms that VELIS is an easy to use and secure tool to make PA approachable, whatever the level of training in healthy subjects.

Episodes of violence suffered by migrants transiting through Libya: a cross-sectional study in "Médecins du Monde's" reception and healthcare centre in Seine-Saint-Denis, France.

INTRODUCTION: The Central Mediterranean Route, passing through Libya, is one of the most dangerous for migrants. Episodes of violence have been documented but have not been accurately quantified. The objective of the study was to estimate the prevalence of episodes of violence suffered in Libya by migrants consulting the Médecins du Monde reception and healthcare centre in Seine-Saint-Denis (Ile-de-France). METHODOLOGY: A monocentric cross-sectional study was conducted from February to May 2019 including migrants over the age of 18 years who had passed through Libya and arrived in Europe from 2017. The presence of emotional distress was considered as exclusion criterion. The proportion, frequency and factors associated to physical, deprivation and sexual violence in Libya were estimated through a bespoke questionnaire, as well as healthcare access in Libya and psychosocial support needs. RESULTS: Ninety eight people were recruited and 72 were interviewed (17 refused to participate and 9 were excluded). 76.4% were men, with a mean age of 31.9 years, 76.4% had low educational level, 66.7% came from Ivory Coast and 59.7% had left their country for security reasons. The median length of stay in Libya was 180 days. The overall proportion of participants having suffered from violence was 96.4% among men and 88.2% among women. The prevalence of physical, deprivation and sexual violence for men and women were 94.2, 81.7 and 18% and 80.0, 86.7 and 53.3%, respectively. Access to healthcare in Libya was 2.8 and 63.9% of participants were oriented to psychosocial support after the interview. CONCLUSIONS: The vast majority of migrants reported having been victims of violence during their transit through Libya. Women were at particular risk of sexual violence. Access to health care in Libya was almost non-existent. Psychosocial support for this population is urgent.

Antibunched Photons Emitted by a dc-Biased Josephson Junction.

We show experimentally that a dc biased Josephson junction in series with a high-enough-impedance microwave resonator emits antibunched photons. Our resonator is made of a simple microfabricated spiral coil that resonates at 4.4 GHz and reaches a 1.97 kΩ characteristic impedance. The second order correlation function of the power leaking out of the resonator drops down to 0.3 at zero delay, which demonstrates the antibunching of the photons emitted by the circuit at a rate of 6×10^{7} photons per second. Results are found in quantitative agreement with our theoretical predictions. This simple scheme could offer an efficient and bright single-photon source in the microwave domain.

Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma.

AIMS: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. METHODS: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. STAKEHOLDERS: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. RESULTS: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU GRANTS 2018: MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). LESSONS LEARNT: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats.

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015).

The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision-making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost-effective treatment strategies.

European symposium on precision medicine in allergy and airways diseases: report of the European Union parliament symposium (October 14, 2015).

On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli and with active participation of the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA) and the Respiratory Effectiveness Group (REG). MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, underlined the importance of the need for a better diagnostic and therapeutic approach for patients with Allergies and Chronic Airways Diseases, and encouraged a joint initiative to control the epidemic of Allergy and Asthma in Europe. The socio-economic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic non-communicable diseases in the EU. Despite the fact that 30% of the total European population is nowadays suffering from allergies and asthma, more than half of these patients are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach in medicine, embracing 4 key features: personalized care based on molecular, immunologic and functional endotyping of the disease, with participation of the patient in the decision making process of therapeutic actions, and taking into account predictive and preventive aspects of the treatment. Implementation of Precision Medicine into clinical practice may help to achieve the arrest of the Epidemic of Allergies and Chronic Airways Diseases. This report summarizes the key messages delivered during the symposium by the speakers, including the EU Commissioner for Health and Food Safety Vitenys Andriukaitis. The Commissioner underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment and cost-effective treatment strategies leading to a better health status of European citizens.

Total body weight loss of ≥ 10 % is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis.

BACKGROUND: Given the rising epidemics of obesity and metabolic syndrome, nonalcoholic steatohepatitis (NASH) is now the most common cause of liver disease in the developed world. Effective treatment for NASH, either to reverse or prevent the progression of hepatic fibrosis, is currently lacking. AIM: To define the predictors associated with improved hepatic fibrosis in NASH patients undergoing serial liver biopsies at prolonged biopsy interval. METHODS: This is a cohort study of 45 NASH patients undergoing serial liver biopsies for clinical monitoring in a tertiary care setting. Biopsies were scored using the NASH Clinical Research Network guidelines. Fibrosis regression was defined as improvement in fibrosis score ≥1 stage. Univariate analysis utilized Fisher's exact or Student's t test. Multivariate regression models determined independent predictors for regression of fibrosis. RESULTS: Forty-five NASH patients with biopsies collected at a mean interval of 4.6 years (±1.4) were included. The mean initial fibrosis stage was 1.96, two patients had cirrhosis and 12 patients (26.7 %) underwent bariatric surgery. There was a significantly higher rate of fibrosis regression among patients who lost ≥10 % total body weight (TBW) (63.2 vs. 9.1 %; p = 0.001) and who underwent bariatric surgery (47.4 vs. 4.5 %; p = 0.003). Factors such as age, gender, glucose intolerance, elevated ferritin, and A1AT heterozygosity did not influence fibrosis regression. On multivariate analysis, only weight loss of ≥10 % TBW predicted fibrosis regression [OR 8.14 (CI 1.08-61.17)]. CONCLUSION: Results indicate that regression of fibrosis in NASH is possible, even in advanced stages. Weight loss of ≥10 % TBW predicts fibrosis regression.