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Abstract During the first postoperative days following minimally invasive sacroiliac joint fusion (MISJF), patients often report serious pain, which contributes to high utilization of painkillers and prevention of early mobilization. This prospective, double-blind randomized controlled trial investigates the effectiveness of intraoperative SIJ infiltration with bupivacaine 0.50% versus placebo (NaCl 0.9%) in 42 patients in reducing postoperative pain after MISJF. The primary outcome was difference in pain between bupivacaine and placebo groups, assessed as fixed factor in a linear mixed model. Secondary outcomes were opioid consumption, patient satisfaction, adverse events, and length of hospital stay. We found that SIJ infiltration with bupivacaine did not affect postoperative pain scores in comparison with placebo, neither as group-effect (p = 0.68), nor dependent on time (group*time: p = 0.87). None of the secondary outcome parameters were affected in the postoperative period in comparison with placebo, including opioid consumption (p = 0.81). To conclude, intra-articular infiltration of the SIJ with bupivacaine at the end of MISJF surgery is not effective in reducing postoperative pain. Hence, we do not recommend routine use of intraoperative SIJ infiltration with analgesia in MISJF.

Patients with low back pain caused by sacroiliac joint (SIJ) dysfunction have an impaired quality of life, due to reported pain, disability and activity limitations. There is increasing evidence that minimally invasive sacroiliac joint fusion (MISJF) results in improvement in pain, disability and quality of life in these patients. Some studies have reported improvements in daily physical activity following MISJF but based on bias-prone self-reports. Our aim was to provide objective data on daily physical activity in patients with SIJ dysfunction. Daily physical activity in daily life of participants was measured using a triaxial accelerometer for seven consecutive days, before surgery and 3 months after surgery. Recorded daily activities were the daily number of events and total time spent sitting or lying, standing, walking, cycling, high-activity and number of steps and sit-to-stand transfers. The quality of life was assessed by the validated Dutch EQ-5D-5 L-questionnaire. No statistical differences were observed between daily physical activity in patients with SIJ dysfunction before and 3 months after MISJF. As compared to matched controls, high-intensity physical activity was lower in both the pre- and postoperative period (p = 0.007) for patients with SIJ dysfunction. The quality of life improved significantly in patients after MSIJF, from 0.418 to 0.797 (p = 0.021) but did not reach the level of controls (1.000). Daily physical activity in patients with postpartum SIJ dysfunction does not improve 3 months following MISJF, while quality of life does improve significantly. The discrepancy between these two observations is food for new research.

Abstract Silicon is indisputably the most advanced material for scalable electronics, but it is a poor choice as a light source for photonic applications, due to its indirect band gap. The recently developed hexagonal Si1−x Ge x semiconductor features a direct bandgap at least for x > 0.65, and the realization of quantum heterostructures would unlock new opportunities for advanced optoelectronic devices based on the SiGe system. Here, we demonstrate the synthesis and characterization of direct bandgap quantum wells realized in the hexagonal Si1−x Ge x system. Photoluminescence experiments on hex-Ge/Si0.2Ge0.8 quantum wells demonstrate quantum confinement in the hex-Ge segment with type-I band alignment, showing light emission up to room temperature. Moreover, the tuning range of the quantum well emission energy can be extended using hexagonal Si1−x Ge x /Si1−y Ge y quantum wells with additional Si in the well. These experimental findings are supported with ab initio bandstructure calculations. A direct bandgap with type-I band alignment is pivotal for the development of novel low-dimensional light emitting devices based on hexagonal Si1−x Ge x alloys, which have been out of reach for this material system until now.

Usutu virus (USUV) is an emerging flavivirus that can infect birds and mammals. In humans, in severe cases, it may cause neuroinvasive disease. The innate immune system, and in particular the interferon response, functions as the important first line of defense against invading pathogens such as USUV. Many, if not all, viruses have developed mechanisms to suppress and/or evade the interferon response in order to facilitate their replication. The ability of USUV to antagonize the interferon response has so far remained largely unexplored. Using dual-luciferase reporter assays we observed that multiple of the USUV nonstructural (NS) proteins were involved in suppressing IFN-β production and signaling. In particular NS4A was very effective at suppressing IFN-β production. We found that NS4A interacted with the mitochondrial antiviral signaling protein (MAVS) and thereby blocked its interaction with melanoma differentiation-associated protein 5 (MDA5), resulting in reduced IFN-β production. The TM1 domain of NS4A was found to be essential for binding to MAVS. By screening a panel of flavivirus NS4A proteins we found that the interaction of NS4A with MAVS is conserved among flaviviruses. The increased understanding of the role of NS4A in flavivirus immune evasion could aid the development of vaccines and therapeutic strategies.

Abstract Background Persistent depressive disorder (PDD) is prevalent and debilitating. For patients with PDD, psychiatric rehabilitation using self-management interventions is advised as the next therapeutic step after multiple unsuccessful treatment attempts. The “Patient and Partner Education Program for All Chronic Diseases” (PPEP4All) is a brief, structured self-management program that focuses on functional recovery for patients and their partners/caregivers. In chronic somatic disorder populations, PPEP4All has already been shown to be clinically effective. We examined whether PPEP4All adapted for PDD (PPEP4All-PDD, nine weekly group or individual sessions) is also clinically effective for adults/elderly with PDD and their partners/caregivers compared to care-as-usual (CAU) in specialized mental healthcare. Methods In this mixed-method multicenter pragmatic randomized controlled trial, 70 patients with PDD and 14 partners/caregivers were allocated to either PPEP4All-PDD (patients, n = 37; partners/caregivers, n = 14) or CAU (patients, n = 33; partners/caregivers, not included) and completed questionnaires at 0, 3, 6, and 12 months regarding depressive symptoms, psychopathology, psychosocial burden, mental resilience, and happiness/well-being. Qualitative data were collected regarding treatment satisfaction. Data were analyzed using mixed model analyses and an intention-to-treat (ITT) approach. Results There was no statistically significant difference in any outcome regarding clinical effectiveness between PPEP4All-PDD and CAU. Subgroup analysis for depressive symptoms did not show any interaction effect for any subgroup. Although 78% of participants recommended PPEP4All-PDD, there was no difference in treatment satisfaction between PPEP4All-PDD (score = 6.6; SD = 1.7) and CAU (score = 7.6; SD = 1.2), p = 0.06. Conclusion Although depressive symptoms did not improve relative to CAU, this only confirmed that treatment for patients with treatment-resistant PDD should move from symptom reduction to functional recovery. Also, functional recovery may be reflected in other outcomes than psychosocial burden, such as self-empowerment, in patients with treatment-resistant PDD. Future research on PPEP4All-PDD could focus on a longer-term program and/or online program that may also be offered earlier in the treatment process as an empowerment intervention. Trial registration Netherlands Trial Register Identifier NL5818. Registered on 20 July 2016 https://clinicaltrialregister.nl/nl/trial/20302

Background: There is a vast amount of evidence supporting the effectiveness of trauma-focused cognitive-behavioral therapy in treating posttraumatic stress disorder (PTSD). However, it remains unclear which specific treatment is most effective for patients with PTSD following childhood sexual and physical abuse (CSPA). Although Imaginal Exposure (IE) has proven highly effective in treating PTSD and is widely acknowledged as a standard method, Imagery Rescripting (IR) may be more suitable for CSPA-related PTSD. IR not only addresses fear but also targets other emotions and cognitions associated with childhood maladaptive schemas. Preliminary findings suggest lower drop-out rates for IR compared to IE, but no Randomized Controlled Trial (RCT) currently assesses the effectiveness of IR for CSPA-related PTSD.Objective: This article presents a study protocol designed to investigate the optimal treatment (IE or IR) for individuals with CSPA-related PTSD and explore predictors of treatment success.Method: In our study protocol, we suggest the inclusion of 173 patients (N = 64 in IR, N = 64 in IE, and N = 45 in the waitlist condition). The therapy procedures for both IE and IR will consist of 16 sessions lasting 90 min each, with treatment durations of 11 weeks. Measurements take place at baseline, at start of treatment, 11 weeks after the start of treatment (after 16 sessions) and at follow-up at 26 weeks after the last session. A mixed regression will be used to compare the three active conditions before and after measurement.Results: This article serves as a study protocol. The results are not yet available but they will be presented in a subsequent article.Conclusion: This study protocol outlines a RCT which will be the first to provide information on the effectiveness of IR versus IE versus a control group in CSPA-related PTSD.Trial registration: Netherlands Trial Register NTR 4817. Registered 26 September 2014.

Summary: Background: The effectiveness of transforaminal lumbar interbody fusion (TLIF) compared to posterior lumbar interbody fusion (PLIF) in patients with single-level spondylolisthesis has not been substantiated. To address the evidence gap, a well-powered randomized controlled non-inferiority trial comparing the effectiveness of TLIF with PLIF, entitled the Lumbar Interbody Fusion Trial (LIFT), was conducted. Methods: In a multicenter randomized controlled non-inferiority trial among five Dutch hospitals, 161 patients were randomly allocated to either TLIF or PLIF (1:1), stratified according to study site. Patients and statisticians were blinded for group assignment. All patients were over 18 years old with symptomatic single-level degenerative, isthmic or iatrogenic lumbar spondylolisthesis, and eligible for lumbar interbody fusion surgery through a posterior approach. The primary outcome was change in disability measured with the Oswestry Disability Index (ODI) from preoperative to one year postoperative. The non-inferiority limit was set to 7.0 points based on the MCID of ODI. Secondary outcomes were change in quality-adjusted life years (QALY) assessed with EuroQol 5 Dimensions, 5 Levels (EQ-5D-5L) and Short Form Health Survey (SF-36), as well as back and leg pain (Numerical rating scale, NRS), anxiety and depression (Hospital Anxiety Depression Scale; HADS), perioperative blood loss, duration of surgery, duration of hospitalization, and complications. Trial registration: Netherlands Trial Registry, number 5722 (registration date March 30, 2016), Lumbar Interbody Fusion Trial (LIFT): A randomized controlled multicenter trial for surgical treatment of lumbar spondylolisthesis. Findings: Patients were included between August 2017 and November 2020. The total study population was 161 patients. Total loss-to-follow-up after one year was 16 patients. Per-protocol analysis included 66 patients in each group. In the TLIF group (mean age 61.6, 36 females), ODI improved from 46.7 to 20.7, whereas in the PLIF group (mean age 61.9, 41 females), it improved from 46.0 to 24.9. This difference (−4.9, 90% CI −12.2 to +2.4) did not reach the non-inferiority limit of 7.0 points in ODI. A significant difference in the secondary outcome measurement, QALY (SF-36), was observed in favor of TLIF (P

Introduction: Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect of voclosporin on SARS-CoV-2 replication than tacrolimus in vitro. We investigated the potential antiviral effects of voclosporin on SARS-CoV-2 in immunocompromised patients. Methods: First, we conducted a prospective, randomized, open-label, proof-of-concept study in 20 kidney transplant recipients (KTRs) on tacrolimus-based immunosuppression who contracted mild to moderate SARS-CoV-2 infection. Patients were randomized to continue tacrolimus or switch to voclosporin. Second, we performed a post hoc analysis on SARS-CoV-2 infections in 216 patients with lupus nephritis (LN) on standard immunosuppression who were randomly exposed to voclosporin or placebo as part of a clinical trial that was conducted during the worldwide COVID-19 pandemic. Results: The primary end point was clearance of SARS-CoV-2 viral load and that did not differ between voclosporin-treated KTRs (median 12 days, interquartile range [IQR] 8–28) and tacrolimus-treated KTRs (median 12 days, IQR 4–16) nor was there a difference in clinical recovery. Pharmacokinetic analyses demonstrated that, when voclosporin trough levels were on-target, SARS-CoV-2 viral load dropped significantly more (ΔCt 7.7 [3.4–10.7]) compared to tacrolimus-treated KTRs (ΔCt 2.7 [2.0-4.3]; P = 0.035). In voclosporin-exposed patients with LN, SARS-CoV-2 infection was detected in 6% (7/116) compared to 12% (12/100) in placebo-exposed patients (relative risk [RR] 1.4 [0.97–2.06]). Notably, no voclosporin-exposed patients with LN died from severe SARS-CoV-2 infection compared to 3% (3/100) in placebo-exposed patients (RR 2.2 [1.90–2.54]). Conclusion: This proof-of-concept study shows a potential positive risk-benefit profile for voclosporin in immunocompromised patients with SARS-CoV-2 infection. These results warrant further investigations on voclosporin to establish an equipoise between infection and maintenance immunosuppression.

Background: Aggressive incidents are common in people with intellectual disabilities. Therefore, we aimed to assess whether supplementation of multivitamins, minerals, and omega-3 fatty acids (FA) reduces aggressive incidents. Methods: We conducted a randomised, triple blind, placebo controlled, single crossover intervention trial. People with intellectual disabilities or borderline intellectual functioning, between 12 and 40 years of age, and showing aggressive behaviour were included. Participants received either a daily dose of dietary supplements, or placebo. Primary outcome was the number of aggressive incidents, measured using the Modified Overt Aggression Scale (MOAS). Results: there were 113 participants (placebo, n = 56), of whom 24 (placebo, n = 10) participated in the crossover phase of the trial. All 137 trajectories were included in the analyses. There was no significant difference in mean number of aggressive incidents per day between those assigned to supplements and those who received placebo (rate ratio = 0.93: 95% Confidence Interval [CI] = 0.59-1.45). Conclusion: In this pragmatic trial, we did not find significant differences in the outcomes between the supplement and placebo arms. The COVID-19 pandemic started midway through our trial, this may have affected the results.

Introduction Atypical antipsychotic (AAP) drugs are the gold-standard treatment for psychotic patients but are nowadays also widely prescribed among people with other mental disorders. Notwithstanding the benefits of AAP in terms of symptom improvement, there are severe adverse effects including the metabolic syndrome. A novel hypothesis is that part of these undesirable effects of antipsychotics could be mediated by their deleterious effects on the microbiome. This may result in dysbiosis, the disruption of bacterial species of the gut microbiota. Recently, dysbiosis has been linked to poor quality of life, depression and anxiety through the gut-brain axis. Mounting evidence proposes that prebiotic consumption may be helpful in the recovery of dysbiosis, although this effect is unclear among long-term antipsychotic users. Objectives The main objective of this study is to assess the potential beneficial effects of the prebiotic Galacto-oligosaccharides (GOS) in combination with 2′-fucosyllactose (2’-FL) on the gut microbiota, by showing a relative increase in Bifidobacteria in fecal samples following intervention. The secondary objective is to assess the effects of GOS on mental wellbeing, sleep, and metabolic parameters. We hypothesize that GOS+2’FL supplementation will improve gut health, mental wellbeing, sleep, and metabolic parameters. Data will be collected 4 weeks prior to the start of the intervention during an observation only phase [t0], at baseline [t1], and after 2 [t2] and 6 [t3] weeks of GOS+2’FL intake. A follow-up will take place at week 10, 4 weeks after the intervention [t4]. Other outcomes that are assessed include the FiberScreen tool, the form of human faeces (Bristol Stool Chart), side effects and the defined daily dosis (DDD) of antipsychotic medication. Methods The study is a single-arm pilot study (non-randomized and non-blinded). We aim to include 30 psychiatric patients on long-term atypical antipsychotic use, irrespective of their specific psychiatric disorder, with a BMI > 25 kg/m2. Following a run-in period of 4 weeks (no intervention but all other aspects of the study), the participants will consume GOSplus (7.0 g BiotisTMGOS + 0.7 g 2’-FL) daily during the first consumption moment of the day (preferably in the morning) for 42 days. The GOSplus powder has a slightly sweet flavour. The primary endpoint is the change in Bifidobacteria in fecal samples from week 0 to week 6. Results The study started recruiting participants in October 2023. Conclusions Conclusions are expected by the end of 2024. Disclosure of Interest None Declared

Background: Healthcare workers (HCW) have faced unprecedented challenges during the COVID-19, with significant impact on their well-being. We aimed to monitor stress-related symptoms and resilience in HCW over time in relation to various factors during the COVID-19 pandemic. Methods: Between June 2020 and May 2022, data was collected among HCW of Leiden University Medical Centre (LUMC) through a digital self-monitoring application. The application included a 14-items self-monitoring tool (i.e., 7-items on Supporting factors, 7-items on Stressful burden), and a set of validated questionnaires (i.e., the Copenhagen Burnout Inventory (CBI), Impact of Event Scale – Revised (IES-R), Resilience Evaluation Scale (RES), and Depression Anxiety and Stress Scale (DASS-21). Results: The self-monitoring tool and validated questionnaires were completed by 1070 and 413 participants respectively. Mean stress-related symptom scores (as measured by the self-monitoring, CBI, IES-R, and DASS-21) exhibited significant changes over time (all p’s < 0.001), which correlated with the waves of COVID-19 patients admitted and the national COVID-19 mortality rate (all p’s < 0.005). Resilience, as measured by the RES, showed a significant decrease from the start of data collection onwards (p = 0.001), whereas supporting factors showed significant decreases the first few months, followed by fluctuations after January 2021 (p = 0.02). Limitations: Selection bias may have arisen as those participating may have been more concerned with the burden on mental wellbeing. Conclusions: The current study underscores the need for active psychosocial support for all HCW particularly during periods of increased admissions due to pandemics.

Abstract Drug development for mood disorders can greatly benefit from the development of robust, reliable, and objective biomarkers. The incorporation of smartphones and wearable devices in clinical trials provide a unique opportunity to monitor behavior in a non-invasive manner. The objective of this study is to identify the correlations between remotely monitored self-reported assessments and objectively measured activities with depression severity assessments often applied in clinical trials. 30 unipolar depressed patients and 29 age- and gender-matched healthy controls were enrolled in this study. Each participant’s daily physiological, physical, and social activity were monitored using a smartphone-based application (CHDR MORE™) for 3 weeks continuously. Self-reported depression anxiety stress scale-21 (DASS-21) and positive and negative affect schedule (PANAS) were administered via smartphone weekly and daily respectively. The structured interview guide for the Hamilton depression scale and inventory of depressive symptomatology–clinical rated (SIGHD-IDSC) was administered in-clinic weekly. Nested cross-validated linear mixed-effects models were used to identify the correlation between the CHDR MORE™ features with the weekly in-clinic SIGHD-IDSC scores. The SIGHD-IDSC regression model demonstrated an explained variance (R2) of 0.80, and a Root Mean Square Error (RMSE) of ± 15 points. The SIGHD-IDSC total scores were positively correlated with the DASS and mean steps-per-minute, and negatively correlated with the travel duration. Unobtrusive, remotely monitored behavior and self-reported outcomes are correlated with depression severity. While these features cannot replace the SIGHD-IDSC for estimating depression severity, it can serve as a complementary approach for assessing depression and drug effects outside the clinic.

The increasing use and effectiveness of primary systemic treatment (PST) enables tailored locoregional treatment. About one third of clinically node positive (cN+) breast cancer patients achieve pathologic complete response (pCR) of the axilla, with higher rates observed in Human Epidermal growth factor Receptor (HER)2-positive or triple negative (TN) breast cancer subtypes. Tailoring axillary treatment for patients with axillary pCR is necessary, as they are unlikely to benefit from axillary lymph node dissection (ALND), but may suffer complications and long-term morbidity such as lymphedema and impaired shoulder motion. By combining pre-PST and post-PST axillary staging techniques, ALND can be omitted in most cN + patients with pCR. Different post-PST staging techniques (MARI/TAD/SN) show low or ultra-low false negative rates for detection of residual disease. More importantly, trials using the MARI (Marking Axillary lymph nodes with Radioactive Iodine seeds) procedure or sentinel lymph node biopsy (SLNB) as axillary staging technique post-PST have already shown the safety of tailoring axillary treatment in patients with an excellent response. Tailored axillary treatment using the MARI procedure in stage I-III breast cancer resulted in 80% reduction of ALND and excellent five-year axillary recurrence free interval (aRFI) of 97%. Similar oncologic outcomes were seen for post-SLNB in stage I-II patients. The MARI technique requires only one invasive procedure pre-NST and a median of one node is removed post-PST, whereas for the SLNB and TAD techniques two to four nodes are removed. A disadvantage of the MARI technique is its use of radioactive iodine, which is subject to extensive regulations.

Background: Total hip arthroplasty is a reliable option to treat osteoarthritis. It reduces pain, increases quality of life, and restores function. The direct anterior approach (DAA), posterior approach (PA), and straight lateral approach (SLA) are mostly used. This systematic review evaluates current literature about costs and cost-effectiveness of DAA, PA, and SLA. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic search, registered in the PROSPERO database (registration number: CRD42021237427), was conducted of databases PubMed, CINAHL, EMBASE, Cochrane, Clinical Trials, Current Controlled Trials, ClinicalTrials.gov, NHS Centre for Review and Dissemination, Econlit, and Web of Science. Eligible studies were randomized controlled trials (RCTs) or comparative cohort studies reporting or comparing costs or cost-effectiveness of either approach as the primary outcome. The risk of bias (RoB) was assessed. For comparison, all costs were converted to American Dollars (reference year 2016). Results: Six systematic review studies were included. RoB ranged from low to high, the level of evidence ranged from 2 to 4, and methodological quality was moderate. Costs ranged from $5313.85 to $15 859.00 (direct) and $1921.00 to $6364.30 (indirect) in DAA. From $5158.46 to $12 344.47 (direct) to $2265.70 to $5566.01 (indirect) for PA and from $3265.62 to $8501.81 (direct) and $2280.16 (indirect) for SLA. Due to heterogeneity of included costs, they were not directly comparable. Solid data about cost-effectiveness cannot be presented. Conclusions: Due to limited and heterogenous evidence about costs and cost-effectiveness, the effect of these in surgical approach is unknown. Further well-powered research to make undisputed conclusions is needed.

Abstract Background In 2012, in The Netherlands a multidisciplinary practice guideline for the assessment and treatment of suicidal behavior was issued. The release of guidelines often fails to change professional behavior due to multiple barriers. Structured implementation may improve adherence to guidelines. This article describes the design of a study measuring the effect of an e-learning supported Train-the-Trainer program aiming at the training of the full staff of departments in the application of the guideline. We hypothesize that both professionals and departments will benefit from the program. Method In a multicenter cluster randomized controlled trial, 43 psychiatric departments spread over 10 regional mental health institutions throughout The Netherlands will be clustered in pairs with respect to the most prevalent diagnostic category of patients and average duration of treatment. Pair members are randomly allocated to either the experimental or the control condition. In the experimental condition, the full staff of departments, that is, all registered nurses, psychologists, physicians and psychiatrists (n = 532, 21 departments) will be trained in the application of the guideline, in a one-day small interactive group Train-the-Trainer program. The program is supported by a 60-minute e-learning module with video vignettes of suicidal patients and additional instruction. In the control condition (22 departments, 404 professionals), the guideline shall be disseminated in the traditional way: through manuals, books, conferences, internet, reviews and so on. The effectiveness of the program will be assessed at the level of both health care professionals and departments. Discussion We aim to demonstrate the effect of training of the full staff of departments with an e-learning supported Train-the-Trainer program in the application of a new clinical guideline. Strengths of the study are the natural setting, the training of full staff, the random allocation to the conditions, the large scale of the study and the willingness of both staff and management to participate in the study. Trial registration Dutch trial register: NTR3092

ABSTRACTThe gut microbiota plays a pivotal role in health and disease. The use of probiotics as microbiota-targeted therapies is a promising strategy to improve host health. However, the molecular mechanisms involved in such therapies are often not well understood, particularly when targeting the small intestinal microbiota. In this study, we investigated the effects of a probiotic formula (Ecologic®825) on the adult human small intestinal ileostoma microbiota. The results showed that supplementation with the probiotic formula led to a reduction in the growth of pathobionts, such as Enterococcaceae and Enterobacteriaceae, and a decrease in ethanol production. These changes were associated with significant alterations in nutrient utilization and resistance to perturbations. These probiotic mediated alterations which coincided with an initial increase in lactate production and decrease in pH were followed by a sharp increase in the levels of butyrate and propionate. Moreover, the probiotic formula increased the production of multiple N-acyl amino acids in the stoma samples. The study demonstrates the utility of network theory in identifying novel microbiota-targeted therapies and improving existing ones. Overall, the findings provide insights into the dynamic molecular mechanisms underlying probiotic therapies, which can aid in the development of more effective treatments for a range of conditions.

Abstract Introduction The Brief Symptom Inventory (BSI), Mood & Anxiety Symptom Questionnaire −30 (MASQ-D30), Short Form Health Survey 36 (SF-36), and Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) are generic instruments that can be used in Routine Outcome Monitoring (ROM) of patients with common mental disorders. We aimed to generate reference values usually encountered in 'healthy' and ‘psychiatrically ill’ populations to facilitate correct interpretation of ROM results. Methods We included the following specific reference populations: 1294 subjects from the general population (ROM reference group) recruited through general practitioners, and 5269 psychiatric outpatients diagnosed with mood, anxiety, or somatoform (MAS) disorders (ROM patient group). The outermost 5% of observations were used to define limits for one-sided reference intervals (95th percentiles for BSI, MASQ-D30 and DAPP-SF, and 5th percentiles for SF-36 subscales). Internal consistency and Receiver Operating Characteristics (ROC) analyses were performed. Results Mean age for the ROM reference group was 40.3 years (SD=12.6) and 37.7 years (SD=12.0) for the ROM patient group. The proportion of females was 62.8% and 64.6%, respectively. The mean for cut-off values of healthy individuals was 0.82 for the BSI subscales, 23 for the three MASQ-D30 subscales, 45 for the SF-36 subscales, and 3.1 for the DAPP-SF subscales. Discriminative power of the BSI, MASQ-D30 and SF-36 was good, but it was poor for the DAPP-SF. For all instruments, the internal consistency of the subscales ranged from adequate to excellent. Discussion and conclusion Reference values for the clinical interpretation were provided for the BSI, MASQ-D30, SF-36, and DAPP-SF. Clinical information aided by ROM data may represent the best means to appraise the clinical state of psychiatric outpatients.

Background: We sought to assess diet quality among people with intellectual disabilities or borderline intellectual functioning, living in residential facilities or receiving day care. Methods: We measured diet quality using the Dutch Healthy Diet Food Frequency Questionnaire (DHD) and compared this between participants with (n = 151) and controls without intellectual disabilities (n = 169). Potential correlates of diet quality were explored. Results: We found lower mean diet quality among people with intellectual disabilities (M = 80.9) compared to controls (M = 111.2; mean adjusted difference -28.4; 95% CI [-32.3, -24.5]; p < 0.001). Participants with borderline intellectual functioning and mild intellectual disabilities had lower diet quality and higher body mass index than individuals with severe to profound intellectual disabilities. Being female was a predictor of better diet quality. Conclusions: Overall, we found that diet quality was low in the sample of people with intellectual disabilities or borderline intellectual functioning.

Abstract Background Better management of affective and somatoform disorders may reduce consultation rates in primary care. Somatoform disorders are highly prevalent in primary care and co-morbidity with affective disorders is substantial, but it is as yet unclear which portion of the health care use may be ascribed to each disorder. Our objective was to investigate the use of primary care for undifferentiated somatoform disorders, other somatoform disorders, anxiety and depressive disorders prospectively. Methods In eight family practices 1046 consulting patients (25–79 yrs) were screened and a stratified sample of 473 was interviewed. Somatoform disorders, anxiety and depressive disorders were diagnosed (DSM IV) using SCAN 2.1. The electronic records of 400 participants regarding somatic diseases, medication and healthcare use were available through their family physicians (FP). Results In the follow-up year patients with psychiatric disorders had more face-to-face contacts with the FP than patients who had no psychiatric disorder: average 7–10 versus 5. The impact on the use of primary care by patients with somatoform disorders was comparable to patients with depressive or anxiety disorders. Undifferentiated somatoform disorders had an independent impact on the use of primary care after adjustment for anxiety and depressive disorders, resulting in 30% more consultations (IRR 1.3 (95% CI: 1.1–1.7)). Anxiety disorders had no independent effect. Conclusion Health care planning should focus on the recognition and treatment of somatoform as well as affective disorders.

Objectives Despite the availability of general and national guidelines for the conduct and reporting of economic evaluations, there is heterogeneity in economic evolutions concerning spine surgery. This is partly the result of differing levels of adherence to the existing guidelines and the lack of disease-specific recommendations for economic evaluations. The extensive heterogeneity in study design, follow-up duration and outcome measurements limit the comparability of economic evaluations in spine surgery. This study has three objectives: (1) to create disease-specific recommendations for the design and conduct of trial-based economic evaluations in spine surgery, (2) to define recommendations for reporting economic evaluations in spine surgery as a complement to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and (3) to discuss methodological challenges and defining the need for future research.Design A modified Delphi method according to the RAND/UCLA Appropriateness Method.Setting A four-step process was followed to create and validate disease-specific statements and recommendations for the conduct and reporting of trial-based economic evaluations in spine surgery. Consensus was defined as >75% agreement.Participants A total of 20 experts were included in the expert group. Validation of the final recommendations was obtained in a Delphi panel, which consisted of 40 researchers in the field who were not included in the expert group.Primary and secondary outcome measures The primary outcome measure is a set of recommendations for the conduct and reporting, as a complement to the CHEERS 2022 checklist, of economic evaluations in spine surgery.Results A total of 31 recommendations are made. The Delphi panel confirmed consensus on all of the recommendations in the proposed guideline.Conclusion This study provides an accessible and practical guideline for the conduct of trial-based economic evaluations in spine surgery. This disease-specific guideline is a complement to existing guidelines, and should aid in reaching uniformity and comparability.

ABSTRACT The gut microbiota plays a crucial role in maintaining overall health and probiotics have emerged as a promising microbiota-targeted therapy for improving human health. However, the molecular mechanisms of probiotics action in general and the targeting of small intestinal microbiota by probiotics are not well understood. To address this, we constructed a synthetic community of three species, which resembles the upper small intestinal microbiota. Our results indicate that probiotic supplementation can directly affect the metabolism of the community, resulting in colonization resistance in a probiotic-specific manner. Supplementation with Streptococcus thermophilus led to increased lactate production and a decrease in pH, while Lactobacillus casei supplementation increased the resistance to perturbations and nutrient utilization without affecting lactate production or pH. Additionally, when combined with kynurenine, Lactobacillus casei enhanced the kynurenine pathway metabolism resulting in elevated kynurenic acid levels and possibly indirect colonization resistance. Overall, our study reveals how selecting probiotics with distinct functional capacities can unlock the full potential of microbiota-targeted therapies. IMPORTANCE The development of probiotic therapies targeted at the small intestinal microbiota represents a significant advancement in the field of probiotic interventions. This region poses unique opportunities due to its low number of gut microbiota, along with the presence of heightened immune and metabolic host responses. However, progress in this area has been hindered by a lack of detailed understanding regarding the molecular mechanisms through which probiotics exert their effects in the small intestine. Our study, utilizing a synthetic community of three small intestinal bacterial strains and the addition of two different probiotic species, and kynurenine as a representative dietary or endogenously produced compound, highlights the importance of selecting probiotic species with diverse genetic capabilities that complement the functional capacity of the resident microbiota, or alternatively, constructing a multispecies formula. This approach holds great promise for the development of effective probiotic therapies and underscores the need to consider the functional capacity of probiotic species when designing interventions.

Giardia and Cryptosporidium are zoonotic protozoan parasites that can infect humans and other taxa, including wildlife, often causing gastrointestinal illness. Both have been identified as One Health priorities in the Arctic, where climate change is expected to influence the distribution of many wildlife and zoonotic diseases, but little is known about their prevalence in local wildlife. To help fill information gaps, we collected fecal samples from four wildlife species that occur seasonally on the northern Alaska coastline or in nearshore marine waters—Arctic fox (Vulpes lagopus), polar bear (Ursus maritimus), Pacific walrus (Odobenus rosmarus divergens), and caribou (Rangifer tarandus)—and used immunofluorescence assays to screen for Giardia cysts and Cryptosporidium oocysts. We detected Giardia cysts in 18.3% and Cryptosporidium oocysts in 16.5% of Arctic foxes (n = 109), suggesting that foxes may be potentially important hosts in this region. We also detected Giardia cysts in a single polar bear (12.5%; n = 8), which to our knowledge represents the first such report for this species. Neither parasite was detected in walruses or caribou.