High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.
ObjectivesTo identify family planning and pregnancy (FPP) issues for female patients of childbearing age living with a chronic inflammatory disease and to assess whether current clinical practice routinely provides adequate support to alleviate these concerns.SettingMultinational survey and an analysis of online patient activity.ParticipantsPremenopausal women (aged 20–45 years; N=969) were surveyed in the USA, the UK, Germany, France, Italy and Spain. Rheumatologists were surveyed in Germany (N=50), France (N=50), Italy (N=50) and the USA (N=100), and gastroenterologists were also surveyed in the USA (N=100).Primary and secondary outcome measuresTwo online surveys were undertaken to identify FPP issues for physicians and patients. The surveys examined the frequency of dialogue on these topics between physicians and patients, alongside assessment of patient satisfaction regarding these conversations. Online analysis identified key themes for patient discussion outside their doctors’ office/clinic/surgery.Results32–56% of physicians spontaneously reported having talked about FPP with their female patients of childbearing age. When prompted, the majority of rheumatologists (74–92%) and gastroenterologists (74%) reported having discussed conception/pregnancy with female patients; however, less than half reported consulting their patient's treating general practitioner/gynaecologist about these topics. The majority of patients reported their FPP-related concerns are not adequately addressed/settled during their medical appointments. Furthermore, only 30–40% of patients considered advice/information to be consistent across multiple healthcare professionals. Key online FPP-related patient discussions included disease state, adverse effects, treatment, switch behaviour and wash-out requirements.ConclusionsFemale patients who live with chronic inflammatory disease have important FPP concerns. The majority of patients, however, do not feel that their FPP concerns are adequately addressed in current clinical practice and report that they receive inconsistent advice from the various healthcare professionals who manage different aspects of their care. There is a clear need for provision of up-to-date and consistent information/support to female patients.
BackgroundThe major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation.MethodsThis is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation.DiscussionDHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial.Trial registrationThe trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283.
The present study aimed to identify barriers and enablers for the implementation of artificial intelligence (AI) in dental, specifically radiographic, diagnostics. Semi-structured phone interviews with dentists and patients were conducted between the end of May and the end of June 2020 (convenience/snowball sampling). A questionnaire developed along the Theoretical Domains Framework (TDF) and the Capabilities, Opportunities and Motivations influencing Behaviors model (COM-B) was used to guide interviews. Mayring’s content analysis was employed to point out barriers and enablers. We identified 36 barriers, conflicting themes or enablers, covering nine of the fourteen domains of the TDF and all three determinants of behavior (COM). Both stakeholders emphasized chances and hopes for AI. A range of enablers for implementing AI in dental diagnostics were identified (e.g., the chance for higher diagnostic accuracy, a reduced workload, more comprehensive reporting and better patient–provider communication). Barriers related to reliance on AI and responsibility for medical decisions, as well as the explainability of AI and the related option to de-bug AI applications, emerged. Decision-makers and industry may want to consider these aspects to foster implementation of AI in dentistry.
Background Due to exposure to potentially infectious aerosols during treatments, the dental personnel is considered being at high risk for aerosol transmitted diseases like COVID-19. The aim of this study was to evaluate aerosol exposure during different dental treatments as well as the efficacy of dental suction to reduce aerosol spreading. Methods Dental powder-jet (PJ; Air-Flow®), a water-cooled dental handpiece with a diamond bur (HP) and water-cooled ultrasonic scaling (US) were used in a simulation head, mounted on a dental unit in various treatment settings. The influence of the use of a small saliva ejector (SE) and high-volume suction (HVS) was evaluated. As a proxy of aerosols, air-born particles (PM10) were detected using a Laser Spectrometer in 30 cm distance from the mouth. As control, background particle counts (BC) were measured before and after experiments. Results With only SE, integrated aerosol levels [median (Q25/Q75) µg/m3 s] for PJ [91,246 (58,213/118,386) µg/m3 s, p < 0.001, ANOVA] were significantly increased compared to BC [7243 (6501/8407) µg/m3 s], whilst HP [11,119 (7190/17,234) µg/m3 s, p > 0.05] and US [6558 (6002/7066) µg/m3 s; p > 0.05] did not increase aerosol levels significantly. The use of HVS significantly decreased aerosol exposure for PJ [37,170 (29,634/51,719) µg/m3 s; p < 0.01] and HP [5476 (5066/5638) µg/m3 s; p < 0.001] compared to SE only, even reaching lower particle counts than BC levels for HP usage (p < 0.001). Conclusions To reduce the exposure to potentially infectious aerosols, HVS should be used during aerosol-forming dental treatments.
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