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Aims and method Research regarding quitting cannabis use often excludes patients with severe mental illness (SMI). We investigated facilitating and impeding factors in SMI patients and their advice to others, using semi-structured interviews with 12 SMI-patients, who were daily cannabis users for ≥12 months and had fully stopped using for ≥6 months. Results Seeking distraction, social contacts in personal environment, avoiding temptation and support from professionals were facilitating factors in stopping. Impeding factors were withdrawal symptoms, user environment, experiencing stress and user's routine. Advice to other patients included to just do it, seek support from others, quit ‘cold turkey’ and acknowledge that cannabis use is a problem. Advice to mental health professionals is to discuss cannabis use from the start of treatment. Clinical implications It is important to inform patients that cannabis use has negative consequences and limits the effects of treatment. Do not judge cannabis use or force the patient to stop.

BackgroundDifficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.MethodsWe queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a neuromuscular blocking agent were assessed.ResultsThe incidence of difficult mask ventilation was 9% (483 of 5453 patients). Infants and patients having increased weight, being less than 5th percentile in weight for age, or having Treacher-Collins syndrome, glossoptosis, or limited mouth opening were more likely to have difficult mask ventilation. Anaesthetic induction using facemask and opioids was associated with decreased risk of difficult mask ventilation. The incidence of complications was significantly higher in patients with "difficult" mask ventilation than in patients without. Rescue placement of a supraglottic airway improved ventilation in 71% (96 of 135) of cases. Administration of neuromuscular blocking agents was more frequently associated with improvement or no change in quality of ventilation than with worsening.ConclusionsCertain abnormalities on physical examination should increase suspicion of possible difficult facemask ventilation. Rescue use of a supraglottic airway device in children with difficult or impossible mask ventilation should be strongly considered.

Abstract Background The deployment of the mental health nurse, an additional healthcare provider for individuals in need of mental healthcare in Dutch general practices, was expected to substitute treatments from general practitioners and providers in basic and specialized mental healthcare (psychologists, psychotherapists, psychiatrists, etc.). The goal of this study was to investigate the extent to which the degree of mental health nurse deployment in general practices is associated with healthcare utilization patterns of individuals with depression. Methods We combined national health insurers’ claims data with electronic health records from general practices. Healthcare utilization patterns of individuals with depression between 2014 and 2019 (N = 31,873) were analysed. The changes in the proportion of individuals treated after depression onset were assessed in association with the degree of mental health nurse deployment in general practices. Results The proportion of individuals with depression treated by the GP, in basic and specialized mental healthcare was lower in individuals in practices with high mental health nurse deployment. While the association between mental health nurse deployment and consultation in basic mental healthcare was smaller for individuals who depleted their deductibles, the association was still significant. Treatment volume of general practitioners was also lower in practices with higher levels of mental health nurse deployment. Conclusion Individuals receiving care at a general practice with a higher degree of mental health nurse deployment have lower odds of being treated by mental healthcare providers in other healthcare settings. More research is needed to evaluate to what extent substitution of care from specialized mental healthcare towards general practices might be associated with waiting times for specialized mental healthcare.

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Background Autologous BCMA-specific CAR T-cell therapies have substantial activity in multiple myeloma (MM). However, due to logistical limitations and BCMAlow relapses, there is a need for alternatives. UCARTCS1 cells are ‘off-the-shelf’ allogeneic CAR T-cells derived from healthy donors targeting SLAMF7 (CS1), which is highly expressed in MM cells. In this study, we evaluated the preclinical activity of UCARTCS1 in MM cell lines, in bone marrow (BM) samples obtained from MM patients and in an MM mouse model.Methods Luciferase-transduced MM cell lines were incubated with UCARTCS1 cells or control (non-transduced, SLAMF7/TCRαβ double knock-out) T-cells at different effector to target ratios for 24 hours. MM cell lysis was assessed by bioluminescence. Anti-MM activity of UCARTCS1 was also evaluated in 29 BM samples obtained from newly diagnosed patients (n=10), daratumumab-naïve relapsed/refractory patients (n=10) and daratumumab-refractory patients (n=9) in 24-hour flow cytometry-based cytotoxicity assays. Finally, UCARTCS1 activity was assessed in mouse xenograft models.Results UCARTCS1 cells induced potent CAR-mediated, and dose-dependent lysis of both MM cell lines and primary MM cells. There was no difference in ex vivo activity of UCARTCS1 between heavily pretreated and newly diagnosed patients. In addition, efficacy of UCARTCS1 was not affected by SLAMF7 expression level on MM cells, proportion of tumor cells, or frequency of regulatory T-cells in BM samples obtained from MM patients. UCARTCS1 treatment eliminated SLAMF7+ non-malignant immune cells in a dose-dependent manner, however lysis of normal cells was less pronounced compared to that of MM cells. Additionally, durable anti-MM responses were observed with UCARTCS1 in an MM xenograft model.Conclusions These results demonstrate that UCARTCS1 has potent anti-MM activity against MM cell lines and primary MM cells, as well as in an MM xenograft model and support the evaluation of UCARTCS1 in patients with advanced MM.

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This study aimed to detect seasonal and species differences in serum 25-hydroxy vitamin D (25(OH)D) concentrations during summer and winter months in captive pachyderms in Europe. Both elephant species had low 25(OH)D while African elephants did not show a seasonal variation. Asian elephants had significantly higher 25(OH)D compared to their African counterparts but also did not show a seasonal difference. Both rhinoceros species investigated had higher 25(OH)D compared to both elephant species; the Indian rhinoceros had high circulating levels year-round, while the black rhinoceroses showed significantly lower 25(OH)D in winter. Malayan tapirs have very low 25(OH)D, comparable to horses. The higher 25(OH)D of elephants and rhinoceroses could indicate that elephants and rhinoceroses are capable of producing vitamin D. This might indicate that the Indian rhinoceroses are capable of producing enough endogenous vitamin D year-round at latitudes around 52° N, while both elephant species and the black rhinoceros are not. This study also showed that it is likely that both elephant species and rhinoceros species are capable of absorbing cholecalciferol from the digestive tract, according to the existing literature, while tapirs may not.

Summary: Background: The Paediatric Difficult Intubation Collaborative identified multiple attempts and persistence with direct laryngoscopy as risk factors for complications in children with difficult tracheal intubations and subsequently engaged in initiatives to reduce repeated attempts and persistence with direct laryngoscopy in children. We hypothesised these efforts would lead to fewer attempts, fewer direct laryngoscopy attempts and decrease complications. Methods: Paediatric patients less than 18 years of age with difficult direct laryngoscopy were enrolled in the Paediatric Difficult Intubation Registry. We define patients with difficult direct laryngoscopy as those in whom (1) an attending or consultant obtained a Cormack Lehane Grade 3 or 4 view on direct laryngoscopy, (2) limited mouth opening makes direct laryngoscopy impossible, (3) direct laryngoscopy failed in the preceding 6 months, and (4) direct laryngoscopy was deferred due to perceived risk of harm or poor chance of success. We used a 5:1 propensity score match to compare an early cohort from the initial Paediatric Difficult Intubation Registry analysis (August 6, 2012–January 31, 2015, 785 patients, 13 centres) and a current cohort from the Registry (March 4, 2017–March 31, 2023, 3925 patients, 43 centres). The primary outcome was first attempt success rate between cohorts. Success was defined as confirmed endotracheal intubation and assessed by the treating clinician. Secondary outcomes were eventual success rate, number of attempts at intubation, number of attempts with direct laryngoscopy, the incidence of persistence with direct laryngoscopy, use of supplemental oxygen, all complications, and severe complications. Findings: First-attempt success rate was higher in the current cohort (42% vs 32%, OR 1.5 95% CI 1.3–1.8, p

Abstract Objectives The black rhinoceros (Diceros bicornis) is an endangered mammal for which a captive breeding program is part of the conservation effort. Black rhinos in zoo’s often suffer from chronic infections and heamochromatosis. Furthermore, breeding is hampered by low male fertility. To aid a research project studying these topics, we sequenced and assembled the genome of a captive male black rhino using ONT sequencing data only. Data description This work produced over 100 Gb whole genome sequencing reads from whole blood. These were assembled into a 2.47 Gb draft genome consisting of 834 contigs with an N50 of 29.53 Mb. The genome annotation was lifted over from an available genome annotation for black rhino, which resulted in the retrieval of over 99% of gene features. This new genome assembly will be a valuable resource in for conservation genetic research in this species. Keywords Black rhinoceros, Diceros bicornis, Genome assembly, Long reads, Whole genome sequencing.

Dry fractionation is low in energy and water use and thus a sustainable option to obtain protein-rich ingredients. Air-classification is used to remove starch from legumes, and electrostatic separation can be used to remove fibres from other starting materials like oilseeds. Flour from oil-rich crops needs to be de-oiled to facilitate dry fractionation, which involves the use of organic solvents or mechanical pressing and might affect the ingredient functionality. This research evaluated if the functionality of soy and lupin is affected by solvent de-oiling and electrostatic separation. Industrially toasted soy and lupin flour contained native protein, which was preserved upon electrostatic separation, de-oiling with hexane and de-oiling with acetone, but ethanol de-oiling resulted in protein denaturation. De-oiling with ethanol or hexane is preferred over de-oiling with acetone based on the flavour profile after de-oiling. The use of different solvents affected the solubility to a different extent and electrostatic separation resulted in a similar or higher solubility of the ingredients (22–49 %), dependent on the solvent, crop and pH condition used. Overall, electrostatic separation resulted in protein-enriched ingredients (43 %DM - 67 %DM Nfactor=5.7) that show potential for application as stabilizers in emulsion-based systems like dressings or frozen foam-based systems like ice-cream.

BackgroundIn settings with limited access to specialist services, differentiating septic arthritis-a surgical emergency-from non-infectious atraumatic arthropathy in paediatric patients is challenging, especially in a setting with a high burden of tuberculosis (TB). We aimed to investigate the aetiologies of swollen, painful joints in an urban setting in South Africa and determine how clinical and laboratory findings varied with diagnosis.Patients and methodsA retrospective review of patients aged 12 or younger presenting to a paediatric hospital in Cape Town, South Africa, with atraumatic swollen, painful joints was conducted over a two year period from 2013 to 2015. Children were excluded if they did not have tissue culture or analysis conducted at our facility. Aetiology was classified as non-infectious, TB septic arthritis, or pyogenic arthritis from other bacterial causes.ResultsOne hundred and four children met inclusion criteria. Arthritis was classified as non-infectious in 43 (41%), TB in 15 (14%), and pyogenic in 40 (38%), with six (6%) patients never receiving a final diagnosis. Mean C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WCC) were all significantly higher in pyogenic infectious arthritis compared with TB and non-infectious arthritis. There were no significant differences in these parameters between non-infectious and TB arthritis. Using cut-point analysis, thresholds were identified predictive of the presence of pyogenic arthritis versus TB or non-infectious arthritis; these included the presence of fever, CRP > 50 mg/L, ESR > 65 mm/h and WCC > 12x109/L. The absence of all of these criteria resulted in a negative predictive value of 100% for pyogenic infection; the presence of three to four criteria resulted in a positive predictive value of 71%.ConclusionsDespite insignificant differences in their clinical presentation compared with non-infectious arthidities, 15% of children were diagnosed with tissue-confirmed TB infection. Predictive values of clinical criteria are reduced in our population due to elevated levels of inflammatory markers in all patients. Synovial biopsy to rule out TB is recommended in all patients in a high-burden setting given clinical similarity to non-infectious aetiologies.

Introduction Successful antiviral therapy has transformed HIV infection into a chronic condition, where optimising quality of life (QoL) has become essential for successful lifelong treatment. Patient-reported outcome measures (PROMs) can signal potential physical and mental health problems related to QoL. This study aims to determine whether PROMs in routine clinical care improve quality of care as experienced by people with HIV (PWH).Methods and analysis We report the protocol of a multicentre longitudinal cohort studying PWH at Amsterdam University Medical Centres in the Netherlands. PROMs are offered annually to patients via the patient portal of the electronic health record. Domains include anxiety, depression, fatigue, sleep disturbances, social isolation, physical functioning, stigma, post-traumatic stress disorder, adherence, drug and alcohol use and screening questions for sexual health and issues related to finances, housing and migration status. Our intervention comprises (1) patients’ completion of PROMs, (2) discussion of PROMs scores during annual consultations and (3) documentation of follow-up actions in an individualised care plan, if indicated. The primary endpoint will be patient-experienced quality of care, measured by the Patient Assessment of Chronic Illness Care, Short Form (PACIC-S). Patients will provide measurements at baseline, year 1 and year 2. We will explore change over time in PACIC-S and PROMs scores and examine the sociodemographical and HIV-specific characteristics of subgroups of patients who participated in all or only part of the intervention to ascertain whether benefit has been achieved from our intervention in all subgroups.Ethics and dissemination Patients provide consent for the analysis of data collected as part of routine clinical care to the AIDS Therapy Evaluation in the Netherlands study (ATHENA) cohort through mechanisms described in Boender et al. Additional ethical approval for the analysis of these data is not required under the ATHENA cohort protocol. The results will be presented at national and international academic meetings and submitted to peer-reviewed journals for publication.

BackgroundInefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure.ObjectivesTo investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE).MethodsIn this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up.ResultsIn 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE.ConclusionsSimilarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

Abstract Identifying biomarkers associated with disease progression and drug resistance are important for personalized care. We investigated the expression of 121 curated genes, related to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) responsiveness. We analyzed 28 human multiple myeloma (MM) cell lines with known drug sensitivities and 130 primary MM patient samples collected at different disease stages, including newly diagnosed (ND), on therapy (OT), and relapsed and refractory (RR, collected within 12 months before the patients’ death) timepoints. Our findings led to the identification of a subset of genes linked to clinical drug resistance, poor survival, and disease progression following combination treatment containing IMIDs and/or PIs. Finally, we built a seven‐gene model (MM‐IMiD and PI sensitivity‐7 genes [IP‐7]) using digital gene expression profiling data that significantly separates ND patients from IMiD‐ and PI‐refractory RR patients. Using this model, we retrospectively analyzed RNA sequcencing (RNAseq) data from the Mulltiple Myeloma Research Foundation (MMRF) CoMMpass (n = 578) and Mayo Clinic MM patient registry (n = 487) to divide patients into probabilities of responder and nonresponder, which subsequently correlated with overall survival, disease stage, and number of prior treatments. Our findings suggest that this model may be useful in predicting acquired resistance to treatments containing IMiDs and/or PIs.

The CD38-targeting antibody daratumumab has marked activity in multiple myeloma (MM). Natural killer (NK) cells play an important role during daratumumab therapy by mediating antibody-dependent cellular cytotoxicity via their FcγRIII receptor (CD16), but they are also rapidly decreased following initiation of daratumumab treatment. We characterized the NK cell phenotype at baseline and during daratumumab monotherapy by flow cytometry and cytometry by time of flight to assess its impact on response and development of resistance (DARA-ATRA study; NCT02751255). At baseline, nonresponding patients had a significantly lower proportion of CD16+ and granzyme B+ NK cells, and higher frequency of TIM-3+ and HLA-DR+ NK cells, consistent with a more activated/exhausted phenotype. These NK cell characteristics were also predictive of inferior progression-free survival and overall survival. Upon initiation of daratumumab treatment, NK cells were rapidly depleted. Persisting NK cells exhibited an activated and exhausted phenotype with reduced expression of CD16 and granzyme B, and increased expression of TIM-3 and HLA-DR. We observed that addition of healthy donor-derived purified NK cells to BM samples from patients with either primary or acquired daratumumab-resistance improved daratumumab-mediated MM cell killing. In conclusion, NK cell dysfunction plays a role in primary and acquired daratumumab resistance. This study supports the clinical evaluation of daratumumab combined with adoptive transfer of NK cells.

S Kor Spoelstra,1,2 Jojanneke Bruins,2 Leonie Bais,2 Paul Seerden,3 Stynke Castelein,2,4 Henderikus Knegtering2,5 1Addiction Care North Netherlands, Groningen, the Netherlands; 2Lentis Psychiatric Institute, Groningen, the Netherlands; 3GGZ Friesland Psychiatric Institute, Leeuwarden, the Netherlands; 4University of Groningen, Faculty of Behavioural and Social Sciences, Department of Clinical Psychology and Experimental Psychopathology, Groningen, the Netherlands; 5University Medical Center Groningen, University of Groningen, Rob Giel Research Center, Groningen, the NetherlandsCorrespondence: S Kor Spoelstra, Addiction care North Netherlands, Leonard Springerlaan 27, Groningen, 9727 KB, the Netherlands, Tel +31503648900, Fax +31503648999, Email k.spoelstra@vnn.nlPurpose: Paliperidone palmitate is the only available long acting injectable (LAI) antipsychotic with a monthly and three-monthly formulation. LAIs may help battle non-adherence. Studies about the experiences of switching from the monthly (PP1M) to the three-monthly formulation (PP3M) of paliperidone are scarce. Therefore, the aim of this study is to evaluate the perspectives of patients, relatives, and mental health professionals on PP3M compared with PP1M.Material and Methods: This was a multicenter, retrospective, non-interventional one-time questionnaire survey among patients with psychotic disorders who switched from PP1M to PP3M (n = 38), their relatives (n = 13) and mental health professionals (n = 38). General satisfaction and (un)desired effects were measured using the Medication Satisfaction Questionnaire (MSQ) and the Subjects’ Reaction to Antipsychotics (SRA), respectively. Additional questionnaires assessed socio-demographic variables, preference, effectiveness, side-effects, and confidence in PP3M compared to PP1M.Results: Mean number of received PP3M injections was 4.2 (SD 2.5). The three study groups reported a high level of confidence in PP3M. High general satisfaction rates about PP3M among patients (69%) and mental health professionals (95%) were reported. The majority of patients, relatives, and mental health professionals reported similar or in some cases even greater effectiveness and similar or in some cases even less side-effects of PP3M compared to PP1M. Sixty-seven percent of the relatives reported less concerns about non-adherence after switching to PP3M.Conclusion: Most patients, relatives, and mental health professionals prefer PP3M over PP1M. The positive attitudes of all parties may facilitate the more frequent use of PP3M and potentially the clinical outcomes.Keywords: paliperidone palmitate 3-monthly, long-acting injectable antipsychotics, psychotic disorders, mental health professionals, family, perspectives

Abstract Background Reduced consciousness has a wide variety of possible causes, not infrequently being toxic in nature. An intoxication might be obvious, but in this paper an unexpected case with a tricyclic antidepressant is presented. Case presentation A 76-year-old caucasian female was found unconscious. Primary diagnostic evaluation, including a negative drugs of abuse test, did not give direction to any clear cause. Yet an intraventricular conductive disorder with widening of the QRS complex and electroencephalogram abnormalities did suggest a possible drug effect. Heteroanamnestic information led to the suspicion of an amitriptyline intoxication, which was confirmed by further laboratory analysis. The patient remained comatose for several days. High concentrations of amitriptyline indicated a large overdose of amitriptyline and, in combination with a cytochrome P450 2D6 poor metabolizer status, could explain the long persistence of her comatose state. Conclusion We present a tricyclic antidepressant intoxication, where the patient is thought to have taken a large amount of amitriptyline at once, which, in combination with a cytochrome P450 2D6 poor metabolizer status, led to an unusual long persistence of her coma.

Meloxicam, a commonly used NSAID, has wide variation in pharmacokinetics between different avian species. The present study hypothesized that meloxicam dosage regimens were similar within, but differ between, groups of avian species with similar feeding habits, habitats, or migratory behaviors. Utilizing the international Zoological Information Management System (ZIMS), drug usage extracts were compiled for meloxicam across eleven major orders of birds. The orders were selected based on their prevalence in zoological collections, wildlife rehabilitation centers, the pet trade, and production environments. Each species with a record available in drug usage extracts was classified into broad categories of main habitat, diet, and migratory status. Significant patterns associated with habitat, diet, or migratory status were not identified statistically. An inverse relationship was identified statistically between the practitioner mg/kg dose and body weight in kg in birds that weigh approximately 20 kg or greater. This study includes practitioner-reported summary data of current doses used in the veterinary field to treat many different avian species. Adverse effects of meloxicam were recorded in <5% of individuals evaluated at the species level in this study. [ABSTRACT FROM AUTHOR]

The Asiatic lion (Panthera leo persica) is an endangered species with a slowly increasing captive and wild population. Several zoos from within the European Association of Zoos and Aquaria Ex Situ Program reported Asiatic lions with neurological signs such as (progressive) ataxia, and stargazing. The aim of this study was to evaluate the frequency (prevalence and incidence) and etiology of these clinical signs within the captive Asiatic lion population. The medical history of 74 Asiatic lions (36 healthy and 38 affected) was retrieved and reviewed for blood tests (biochemical, hematological, and retinol), diagnostic imaging (MRI and CT scans) and postmortem examinations. The data of the affected lions was compared with those of healthy lions. Between 2002 and 2020, the prevalence of ataxia ranged from 0.6% in 2004 to 13.0% in 2020. The incidence of ataxia was variable per year between 2002 and 2020 and ranged between 0 and 40%. Besides ataxia, stiffness and lameness were the most described signs in this study. Blood results showed lower total protein, ALT and creatinine, and higher phosphate in lions with neurological signs. Moreover, neurologically affected lions showed a significant lower blood retinol than the control lions (0.59–0.81 µmol/L). The most important finding in diagnostic imaging and necropsy included caudal fossa hyperostosis and cerebellar herniation. These abnormalities are similar as found in African lions (Panthera leo) with calvarial hyperostosis syndrome associated with vitamin A deficiency. Leucomyelopathy, syringomyelia (in one case combined with cerebellar herniation) and incidental mineralization of the dura mater were also described. A possible congenital/hereditary component should not be excluded. [ABSTRACT FROM AUTHOR]

Abstract Background Rapid antigen diagnostic tests (Ag-RDTs) are the most widely used point-of-care tests for detecting SARS-CoV-2 infection. Since the accuracy may have altered by changes in SARS-CoV-2 epidemiology, indications for testing, sampling and testing procedures, and roll-out of COVID-19 vaccination, we evaluated the performance of three prevailing SARS-CoV-2 Ag-RDTs. Methods In this cross-sectional study, we consecutively enrolled individuals aged >16 years presenting for SARS-CoV-2 testing at three Dutch public health service COVID-19 test sites. In the first phase, participants underwent either BD-Veritor System (Becton Dickinson), PanBio (Abbott), or SD-Biosensor (Roche Diagnostics) testing with routine sampling procedures. In a subsequent phase, participants underwent SD-Biosensor testing with a less invasive sampling method (combined oropharyngeal-nasal [OP-N] swab). Diagnostic accuracies were assessed against molecular testing. Results Six thousand nine hundred fifty-five of 7005 participants (99%) with results from both an Ag-RDT and a molecular reference test were analysed. SARS-CoV-2 prevalence and overall sensitivities were 13% (188/1441) and 69% (129/188, 95% CI 62–75) for BD-Veritor, 8% (173/2056) and 69% (119/173, 61–76) for PanBio, and 12% (215/1769) and 74% (160/215, 68–80) for SD-Biosensor with routine sampling and 10% (164/1689) and 75% (123/164, 68–81) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72–83% and 54–56%, respectively. Above a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities were 86% (125/146, 79–91) for BD-Veritor, 89% (108/121, 82–94) for PanBio, and 88% (160/182, 82–92) for SD-Biosensor with routine sampling and 84% (118/141, 77–89) with OP-N sampling. Specificities were >99% for all tests in most analyses. Sixty-one per cent of false-negative Ag-RDT participants returned for testing within 14 days (median: 3 days, interquartile range 3) of whom 90% tested positive. Conclusions Overall sensitivities of three SARS-CoV-2 Ag-RDTs were 69–75%, increasing to ≥86% above a viral load cut-off. The decreased sensitivity among asymptomatic participants and high positivity rate during follow-up in false-negative Ag-RDT participants emphasise the need for education of the public about the importance of re-testing after an initial negative Ag-RDT should symptoms develop. For SD-Biosensor, the diagnostic accuracy with OP-N and deep nasopharyngeal sampling was similar; adopting the more convenient sampling method might reduce the threshold for professional testing.

The development of novel and sustainable food products, such as cheese- and meat analogues, requires a better understanding of the use of less refined ingredients. We investigated the distribution of water between the protein and starch phase of doughs and heat-induced gels made from air-classified faba bean fractions by developing a method suited for investigation of such multi-component ingredients. The moisture contents of the protein and starch phases in the dough were determined using a method based on partial sorption isotherms of mixed doughs of protein- and starch-rich fractions at high water activity. Water content of the protein phase is higher than that of the starch phase in dough, showing that protein takes up more water than starch at room temperature. Also, the moisture content of the protein phase in the gels was calculated using a model based on the denaturation temperature of legumin. From the experiments and the modelling, it became evident that the moisture content of the protein phase in the gel is lower than the moisture content of the protein phase in the dough, showing the importance of considering moisture migration from the protein to the starch during heating.

Abstract Purpose Various sustained‐release formulations incorporate high bupivacaine concentrations but data on local toxicity is lacking. This study explores local toxic effects of highly concentrated (5%) bupivacaine compared to clinically used concentrations in vivo following skeletal surgery, to assess the safety of sustained‐release formulations with high bupivacaine concentrations. Methods Sixteen rats underwent surgery, in which screws with catheters affixed were implanted in the spine or femur in a factorial experimental design, allowing single‐shot or continuous 72 h local administration of 0.5%, 2.5% or 5.0% bupivacaine hydrochloride. During the 30‐day follow‐up, animal weight was recorded and blood samples were obtained. Implantation sites underwent histopathological scoring for muscle damage, inflammation, necrosis, periosteal reaction/thickening and osteoblast activity. Effects of bupivacaine concentration, administration mode and implantation site on local toxicity scores were analyzed. Results Chi‐squared tests for score frequencies revealed a concentration‐dependent decrease in osteoblast count. Moreover, spinal screw implantation led to significantly more muscle fibrosis but less bone damage than femoral screw implantation, reflecting the more invasive muscle dissection and shorter drilling times related to the spinal procedure. No differences between bupivacaine administration modes regarding histological scoring or body weight changes were observed. Weight increased, while CK levels and leukocyte counts decreased significantly during follow‐up, reflecting postoperative recovery. No significant differences in weight, leukocyte count and CK were found between interventional groups. Conclusion This pilot study found limited concentration‐dependent local tissue effects of bupivacaine solutions concentrated up to 5.0% following musculoskeletal surgery in the rat study population.

Background Hospitalisations for heart failure are frequent and costly, linked with a lower quality of life, and lead to higher morbidity and mortality. Home hospitalisation interventions could be a substitute for in-hospital stays to reduce the burden on patients. The current study aims to investigate patient-reported satisfaction and usability in combination with the safety of a digital health-supported home hospitalisation intervention for heart failure patients. Methods We conducted an international, multicentre, single-arm, interventional study to investigate the feasibility and safety of a digital health-supported home hospitalisation platform. Patients with acute decompensation of known and well-assessed chronic heart failure with an indication for hospital admission were included. The primary outcome was patient satisfaction. Secondary outcomes were usability, adherence, and safety. Results A total number of 66 patients were included, of which the data of 65 patients (98.5%) was analysed. A total of 86.1% of patients reported being very satisfied or totally satisfied. No patients reported to be not satisfied with the home hospitalisation intervention. The patients reported a sufficient usability score (mean score: 75.8% of 100%) for the digital health-supported home hospitalisation platform. The adherence to the daily measurements of blood pressure and weight was very high, whereas the adherence to the daily interaction with the eCoach was lower (69.3%). In 7 patients (10.8%), a conversion from home hospitalisation to regular hospitalisation was needed. Furthermore, 6 patients (9.2%) had rehospitalisation within 30 days after the end of the home hospitalisation intervention. Conclusion A digitally supported home hospitalisation intervention is feasible. This study demonstrates high patient satisfaction and sufficiently high usability scores. The safety outcomes are comparable with traditional heart failure hospitalisations. This indicates that digitally supported home hospitalisation could be an alternative to in-hospital care for all age groups, yet further research is needed to prove the (cost-) effectiveness.

Protection of ecosystem services is increasingly emphasized as a risk-assessment goal, but there are wide gaps between current ecological risk-assessment endpoints and potential effects on services provided by ecosystems. The authors present a framework that links common ecotoxicological endpoints to chemical impacts on populations and communities and the ecosystem services that they provide. This framework builds on considerable advances in mechanistic effects models designed to span multiple levels of biological organization and account for various types of biological interactions and feedbacks. For illustration, the authors introduce 2 case studies that employ well-developed and validated mechanistic effects models: the inSTREAM individual-based model for fish populations and the AQUATOX ecosystem model. They also show how dynamic energy budget theory can provide a common currency for interpreting organism-level toxicity. They suggest that a framework based on mechanistic models that predict impacts on ecosystem services resulting from chemical exposure, combined with economic valuation, can provide a useful approach for informing environmental management. The authors highlight the potential benefits of using this framework as well as the challenges that will need to be addressed in future work. Environ Toxicol Chem 2017;36:845-859. © 2017 SETAC.

The blood-brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism. In this study, we examine links between central monoamine metabolite levels and whole-blood gene expression to better understand the connection between peripheral systems and the CNS. To that end, we correlated the prime monoamine metabolites in cerebrospinal fluid (CSF) with whole-genome gene expression microarray data from blood (N=240 human subjects). We additionally applied gene-enrichment analysis and weighted gene co-expression network analyses (WGCNA) to identify modules of co-expressed genes in blood that may be involved with monoamine metabolite levels in CSF. Transcript levels of two genes were significantly associated with CSF serotonin metabolite levels after Bonferroni correction for multiple testing: THAP7 (P=2.8 × 10-8, β=0.08) and DDX6 (P=2.9 × 10-7, β=0.07). Differentially expressed genes were significantly enriched for genes expressed in the brain tissue (P=6.0 × 10-52). WGCNA revealed significant correlations between serotonin metabolism and hub genes with known functions in serotonin metabolism, for example, HTR2A and COMT. We conclude that gene expression levels in whole blood are associated with monoamine metabolite levels in the human CSF. Our results, including the strong enrichment of brain-expressed genes, illustrate that gene expression profiles in peripheral blood can be relevant for quantitative metabolic phenotypes in the CNS.

Introduction Most research on COVID-19 effects has focused on the general population. Here we measure its impact on Dutch FACT and autism outpatient service users during both waves. Objectives This study aimed to: 1) investigate participants’ mental health, 2) assess experiences with outpatient services, and 3) assess respondents’ experiences with governmental measures in the Netherlands during the first and second wave of COVID-19. Methods Respondents (wave 1: n=100; wave 2: n=150) reported on mental health, experiences with outpatient care, government measures and information services in an online survey. Results Findings demonstrate happiness was rated an average of 6 out of 10, 70% of respondents scored below average on resilience, positive consequences for mental health (ordered world, reflection time) during both waves were similar, and prominent negative consequences included decreased social interactions and increased or new problems regarding mental health and daily functioning from wave 1-2. Lifestyle changed in 50% in both waves, although only slightly attributed to the pandemic. Substance use during both waves hardly changed. Mental healthcare continuation was highly appreciated in both waves (75-80% scored ≥7 on 10-point scale). (Video)calling was the most frequently mentioned positive care experience; missing face-to-face contact with care providers considered most negative. COVID-19 measures were less doable in the second wave. Vaccination willingness approximated 70%. Conclusions Results show a nuanced, but clear picture of experiences during both waves. Continuation of services through tele-health was well-received. Monitoring of long-term impact is needed. Disclosure No significant relationships.