Author Correction: Self-verifying variational quantum simulation of lattice models.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Self-verifying variational quantum simulation of lattice models.

Hybrid classical-quantum algorithms aim to variationally solve optimization problems using a feedback loop between a classical computer and a quantum co-processor, while benefiting from quantum resources. Here we present experiments that demonstrate self-verifying, hybrid, variational quantum simulation of lattice models in condensed matter and high-energy physics. In contrast to analogue quantum simulation, this approach forgoes the requirement of realizing the targeted Hamiltonian directly in the laboratory, thus enabling the study of a wide variety of previously intractable target models. We focus on the lattice Schwinger model, a gauge theory of one-dimensional quantum electrodynamics. Our quantum co-processor is a programmable, trapped-ion analogue quantum simulator with up to 20 qubits, capable of generating families of entangled trial states respecting the symmetries of the target Hamiltonian. We determine ground states, energy gaps and additionally, by measuring variances of the Schwinger Hamiltonian, we provide algorithmic errors for the energies, thus taking a step towards verifying quantum simulation.

Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial.

BACKGROUND: Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. OBJECTIVE: To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. DESIGN: Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. SUBJECTS: Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160 mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4 months (planned sample size n = 492). MEASUREMENTS: Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16 weeks. RESULTS: From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. CONCLUSION: Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.

Frequencies and reasons for unplanned emergency department return visits by older adults: a cohort study.

BACKGROUND: As unplanned Emergency Department (ED) return visits (URVs) are associated with adverse health outcomes in older adults, many EDs have initiated post-discharge interventions to reduce URVs. Unfortunately, most interventions fail to reduce URVs, including telephone follow-up after ED discharge, investigated in a recent trial. To understand why these interventions were not effective, we analyzed patient and ED visit characteristics and reasons for URVs within 30 days for patients aged ≥ 70 years. METHODS: Data was used from a randomized controlled trial, investigating whether telephone follow-up after ED discharge reduced URVs compared to a satisfaction survey call. Only observational data from control group patients were used. Patient and index ED visit characteristics were compared between patients with and without URVs. Two independent researchers determined the reasons for URVs and categorized them into: patient-related, illness-related, new complaints and other reasons. Associations were examined between the number of URVs per patient and the categories of reasons for URVs. RESULTS: Of the 1659 patients, 222 (13.4%) had at least one URV within 30 days. Male sex, ED visit in the 30 days before the index ED visit, triage category "urgent", longer length of ED stay, urinary tract problems, and dyspnea were associated with URVs. Of the 222 patients with an URV, 31 (14%) returned for patient-related reasons, 95 (43%) for illness-related reasons, 76 (34%) for a new complaint and 20 (9%) for other reasons. URVs of patients who returned ≥ 3 times were mostly illness-related (72%). CONCLUSION: As the majority of patients had an URV for illness-related reasons or new complaints, these data fuel the discussion as to whether URVs can or should be prevented. TRIAL REGISTRATION: For this cohort study, we used data from a randomized controlled trial (RCT). This trial was pre-registered in the Netherlands Trial Register with number NTR6815 on the 7th of November 2017.

Is there a link between headache and cognitive disorders? A systematic review.

BACKGROUND: The overall prevalence of headaches decreases with age; however headaches remain frequent in aged individuals who are also affected by other disorders such as cognitive decline. Despite the high frequency of both conditions in these persons, the association between headaches and cognitive decline is underexplored, underdiagnosed and poorly understood. OBJECTIVE: In the present article, we aim to provide a comprehensive review of existing data concerning the link between headache and cognitive decline. METHODS: We undertook a systematic literature review to report articles that focus on headaches (including all types of headaches) and neurocognitive disorders of degenerative causes. RESULTS: Only 9 studies have explored the association between headaches and neurocognitive decline. Methods were highly variable from population-based study to short series of patients using either database or questionnaire during consultation. Studies focusing on Familial Alzheimer's Disease revealed a very high prevalence of headaches in mutation carrier patients compared to non-carrier patients. CONCLUSION: The association between headaches and cognitive decline is underexplored. Future studies are needed to address the pathophysiological mechanisms to improve the treatment of these underestimated headaches.

A Water-Soluble Iridium Photocatalyst for Chemical Modification of Dehydroalanines in Peptides and Proteins.

Dehydroalanine (Dha) residues are attractive noncanonical amino acids that occur naturally in ribosomally synthesised and post-translationally modified peptides (RiPPs). Dha residues are attractive targets for selective late-stage modification of these complex biomolecules. In this work, we show the selective photocatalytic modification of dehydroalanine residues in the antimicrobial peptide nisin and in the proteins small ubiquitin-like modifier (SUMO) and superfolder green fluorescent protein (sfGFP). For this purpose, a new water-soluble iridium(III) photoredox catalyst was used. The design and synthesis of this new photocatalyst, [Ir(dF(CF3 )ppy)2 (dNMe3 bpy)]Cl3 , is presented. In contrast to commonly used iridium photocatalysts, this complex is highly water soluble and allows peptides and proteins to be modified in water and aqueous solvents under physiologically relevant conditions, with short reaction times and with low reagent and catalyst loadings. This work suggests that photoredox catalysis using this newly designed catalyst is a promising strategy to modify dehydroalanine-containing natural products and thus could have great potential for novel bioconjugation strategies.

Revised guidelines of the French headache society for the diagnosis and management of migraine in adults. Part 3: Non-pharmacological treatment.

The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the third part of the guidelines, which is focused on the non-pharmacological treatment of migraine, including physical exercise, dietary supplements and plants, diets, neuromodulation therapies, acupuncture, behavioral interventions and mindfulness therapy, patent foramen ovale closure and surgical nerve decompression.

Revised guidelines of the French headache society for the diagnosis and management of migraine in adults. Part 2: Pharmacological treatment.

The French Headache Society proposes updated French guidelines for the management of migraine. This article presents the second part of the guidelines, which is focused on the pharmacological treatment of migraine, including both the acute treatment of attacks and the prophylaxis of episodic migraine as well as chronic migraine with and without medication overuse. The specific situations that can be encountered in women with migraine are also discussed, including pregnancy, menstrual migraine, contraception and hormonal replacement therapy.

Revised guidelines of the French Headache Society for the diagnosis and management of migraine in adults. Part 1: Diagnosis and assessment.

The French Headache Society proposes updated French guidelines for the management of migraine. The first part of these recommendations is focused on the diagnosis and assessment of migraine. First, migraine needs to be precisely diagnosed according to the currently validated criteria of the International Classification of Headache Disorders, 3d version (ICHD-3). Migraine-related disability has to be assessed and we suggest to use the 6 questions of the headache impact test (HIT-6). Then, it is important to check for risk factors and comorbidities increasing the risk to develop chronic migraine, especially frequency of headaches, acute medication overuse and presence of depression. We suggest to use a migraine calendar and the Hospital Anxiety and Depression scale (HAD). It is also necessary to evaluate the efficacy and tolerability of current migraine treatments and we suggest to systematically use the self-administered Migraine Treatment Optimization Questionnaire (M-TOQ) for acute migraine treatment. Finally, a treatment strategy and a follow-up plan have to be proposed. Guidelines for pharmacological and non-pharmacological treatments are presented in the second and third part of the recommendations.

(Vi)-rushed Into Online Group Schema Therapy Based Day-Treatment for Older Adults by the COVID-19 Outbreak in the Netherlands.

BACKGROUND: Societal measures in context of the COVID-19 outbreak forced us to transform our schema therapy based day-treatment for older adults with chronic affective disorders and personality problems into an online program. The objective of this paper is to present first impressions of this transformation. METHODS: Using over-the-phone instructions initially, all patients were able to participate with the online therapy program. To reduce screen-time for patients, the nonverbal therapies were shortened. Four patients, aged 64-70 years, started our online program. RESULTS: Therapists were positive about the online capabilities and resilience of patients to adapt to the new situation. Prejudices on limited effectiveness of online psychotherapy were counteracted. Sending homework by email and mail seems to facilitate therapy adherence. Nonverbal therapy could be important to stimulate the online group process. CONCLUSION: We were positively surprised by the online capabilities of our geriatric mental healthcare patients and encourage further formal effectiveness studies.

Symptom Profile and Clinical Course of Inpatients with Unipolar versus Bipolar Depression.

BACKGROUND: Although differences in symptom profiles and outcome between depressive patients with an underlying major depressive disorder (MDD) and bipolar depression (BD) have been reported, studies with sequential short-interval assessments in a real-life inpatient setting are scarce. OBJECTIVES: To examine potential differences in symptom profile and course of depressive symptomatology in depressive inpatients with underlying MDD and BD. METHODS: A cohort of 276 consecutive inpatients with MDD (n = 224) or BD (n = 52) was followed during their hospitalization using routine outcome monitoring (ROM), which included a structured diagnostic interview at baseline (Mini-International Neuropsychiatric Interview Plus [MINI-Plus]) and repeated 17-item Hamilton Depression Rating Scale every 2 weeks. MDD and BD were compared regarding their symptom profiles and time to response and remission. Furthermore, the concordance between the MINI-Plus and clinical diagnosis was analyzed. RESULTS: Patients were on average 52 and 47 years old in the MDD and BD group, respectively, and 66 versus 64% were female. Compared to patients with BD, patients with MDD scored higher on weight loss (p = 0.02), whereas the BD group showed a higher long-term likelihood of response (hazard ratio = 1.93, 95% confidence interval 1.16-3.20, p for interaction with time = 0.04). Although the same association was seen for remission, the interaction with time was not significant (p = 0.48). Efficiency between the MINI-Plus and clinical diagnosis of BD was high (0.90), suggesting that the MINI-Plus is an adequate ROM diagnostic tool. CONCLUSIONS: In routine clinical inpatient care, minor differences in the symptom profile and the course of depressive symptomatology may be helpful in distinguishing MDD and BD, particularly when using sequential ROM assessments.

Cationic iron porphyrins with sodium dodecyl sulphate for micellar catalysis of cyclopropanation reactions.

Here, we report that the combination of cationic iron porphyrins with sodium dodecyl sulphate (SDS) gives rise to efficient micellar catalysis of cyclopropanation reactions of styrene derivatives, using diazoacetates as carbene precursors. This simple, yet effective approach for cyclopropanations illustrates the power of micellar catalysis.

Effects of tocolysis with nifedipine or atosiban on child outcome: follow-up of the APOSTEL III trial.

OBJECTIVE: To compare the long-term effects of tocolysis with nifedipine or atosiban on child outcome at age 2.5-5.5 years. DESIGN: The APOSTEL III trial was a multicentre randomised controlled trial that compared tocolysis with nifedipine or atosiban in 503 women with threatened preterm birth. Neonatal outcomes did not differ between both treatment arms, except for a higher incidence of intubation in the atosiban group. METHODS: Parents were asked to complete four questionnaires regarding neurodevelopment, executive function, behaviour problems and general health. MAIN OUTCOME MEASURES: The main long-term outcome measure was a composite of abnormal development at the age of 2.5-5.5 years. RESULTS: Of the 426 women eligible for follow-up, 196 (46%) parents returned the questionnaires for 115 children in the nifedipine group and 110 children in the atosiban group. Abnormal development occurred in 32 children (30%) in the nifedipine group and in 38 children (38%) in the atosiban group (OR 0.74, 95% CI 0.41-1.34). The separate outcomes for neurodevelopment, executive function, behaviour, and general health showed no significant differences between the groups. Sensitivity analysis for all children of the APOSTEL III trial, including a comparison of deceased children, resulted in a higher rate of healthy survival in the nifedipine group (64 versus 54%), but there was no significant difference in the overall mortality rate (5.4 versus 2.7%). There were no significant subgroup effects. CONCLUSION: Outcomes on broad child neurodevelopment, executive function, behaviour and general health were comparable in both groups. Neither nifedipine nor atosiban can be considered as the preferred treatment for women with threatened preterm birth. TWEETABLE ABSTRACT: Nifedipine- and atosiban-exposed children had comparable long-term outcomes, including neurodevelopment, executive function and behaviour.

Quasiparticle engineering and entanglement propagation in a quantum many-body system.

The key to explaining and controlling a range of quantum phenomena is to study how information propagates around many-body systems. Quantum dynamics can be described by particle-like carriers of information that emerge in the collective behaviour of the underlying system, the so-called quasiparticles. These elementary excitations are predicted to distribute quantum information in a fashion determined by the system's interactions. Here we report quasiparticle dynamics observed in a quantum many-body system of trapped atomic ions. First, we observe the entanglement distributed by quasiparticles as they trace out light-cone-like wavefronts. Second, using the ability to tune the interaction range in our system, we observe information propagation in an experimental regime where the effective-light-cone picture does not apply. Our results will enable experimental studies of a range of quantum phenomena, including transport, thermalization, localization and entanglement growth, and represent a first step towards a new quantum-optic regime of engineered quasiparticles with tunable nonlinear interactions.

Routine alcohol screening in the ED: unscreened patients have an increased risk for hazardous alcohol use.

BACKGROUND: Routine screening programmes for hazardous alcohol use in the ED miss large numbers of patients. We investigated whether patient-related or staff-related factors cause screening failures and whether unscreened patients are at increased risk of hazardous alcohol use. METHODS: This is a secondary analysis of a prospective study. From November 2012 to November 2013, all adult patients visiting a Dutch inner city ED were screened for hazardous alcohol consumption using the Alcohol Use Disorders Identification Test-Consumption. Reasons for failure of screening were categorised as: (A) patient is unable to cooperate (due to illness or pain, decreased consciousness or incomprehension due to intoxication, psychiatric, cognitive or neurological disorder or language barrier), (B) healthcare professional forgot to ask, (C) patient refuses cooperation and (D) screening was recently performed (<6 months ago). Presence of risk factors for hazardous alcohol use was compared between screened and unscreened patients. RESULTS: Of the 28 019 ED patients, 18 310 (65%) were screened and 9709 (35%) were not. In 7150 patients staff forgot to screen, whereas 2559 patients were not screened due to patient factors (2340 being unable and 219 unwilling). Patients with any of these risk factors were less likely to be screened: male sex, alcohol-related visit, any intoxication, head injury, any kind of wound and major trauma. In multivariate analysis, all these risk factors were independently associated with not being screened. Patients with at least one risk factor for hazardous alcohol use were less likely to be screened. Highest prevalence of risk factors was found in patients unable or unwilling to cooperate. CONCLUSION: Patients who do not undergo routine screening for alcohol use at triage in the ED have an increased risk for hazardous alcohol use. These data highlight the importance of screening patients, especially those initially unwilling or unable to cooperate, at a later stage.

Cognitive Deficits in Older Adults With Psychotic Depression: A Meta-Analysis.

A major depressive disorder with psychotic features, that is, psychotic depression (PD), is often accompanied by cognitive deficits, particularly in older patients. We aimed to assess to what extent various cognitive domains are affected in older patients with PD compared to those with nonpsychotic depression (NPD). Therefore, a systematic search was conducted in Medline, Embase, Web of Science, the Cumulative Index to Nursing and Allied Literature (CINAHL), Google Scholar, and Cochrane for all relevant studies. Hereafter, we conducted a meta-analysis of seven studies on cognitive deficits in older adults (55+ years), comparing patients with PD and patients with NPD. Compared to patients with NPD, those with PD not only showed a significantly poorer performance on overall cognitive function, with a Hedges' g effect size of -0.34 (95% confidence interval: -0.56; -0.12; p = 0.003), but also on nearly all separate cognitive domains, with Hedges' g effect sizes ranging from -0.26 to -0.64 (all p's <0.003), of which attention was most adversely affected. Verbal fluency showed no significant effect, although this analysis may have been underpowered. The funnel plot suggested no significant publication bias (Egger test intercept: -2.47; 95% confidence interval: -5.50; 0.55; p = 0.09). We conclude that older patients with PD show more cognitive deficits on all cognitive domains, except for verbal fluency, compared to patients with NPD. It is crucial that clinicians and researchers take cognitive deficits into consideration in older adults with PD.

Efficacy and Tolerability of Atypical Antipsychotics in the Treatment of Delirium: A Systematic Review of the Literature.

BACKGROUND: Although haloperidol is the most widely used drug in the treatment of delirium, evidence on the relevance of atypical antipsychotics (AAPs) is growing. OBJECTIVE: To review the literature on the efficacy and tolerability of AAPs in the treatment of delirium. METHODS: A systematic search of the literature published before April 2018 was performed on PubMed using the following search strings: "Delirium" and "Atypical antipsychotics", "Novel antipsychotics", "New antipsychotics", "Quetiapine", "Olanzapine", "Aripiprazole", "Risperidone", "Paliperidone", "Clozapine", "Asenapine", "Iloperidone", "Amisulpiride", "Ziprasidone", "Zotepine", "Sertindole", "Lurasidone" or "Perospirone". RESULTS: Twelve randomized controlled trials (RCTs) and 22 open trials were considered. Despite an overall lack of large-scale RCTs, there is some evidence supporting the efficacy of olanzapine and quetiapine in placebo controlled trials. In a recent and large RCT in elderly patients, risperidone and/or haloperidol were associated with a significantly worse outcome than placebo. While preliminary, the current comparative studies suggest that haloperidol and the AAPs olanzapine, quetiapine and risperidone are similarly effective, although treatment with AAPs is associated with a reduced incidence of extrapyramidal symptoms. Ziprasidone was not shown to be effective. No RCTs are available for other AAPs. CONCLUSIONS: Although the current evidence of the efficacy and tolerability of AAPs in the treatment of delirium is limited and the heterogeneity of the data precluded a meta-analysis, olanzapine and quetiapine seem to be adequate alternatives to haloperidol, especially in patients who are vulnerable for extrapyramidal symptoms, who require sedation or who have a history of haloperidol intolerance. Evidently, larger-scale RCTs are urgently required.

Associations between testosterone and metabolic syndrome in depressed and non-depressed older men and women.

OBJECTIVES: Older age and major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and metabolic syndrome (MetS) in men, although associations in women are less clear. Therefore, we investigated whether testosterone is associated with MetS and whether this association is different for depressed and non-depressed older men and women. METHODS: In this prospective cohort study, 478 participants (349 patients with MDD and 129 controls) aged between 60 and 93 years from the Netherlands Study of Depression in Older Persons were included. Total testosterone (TT) and sex-hormone binding globulin levels were measured using a second-generation radioimmune assay. Free testosterone (FT) was calculated based on TT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: A higher risk for MetS was found in men with low FT and TT (odds ratio [OR]: 0.67, 95% confidence interval [95%CI]: 0.47-0.95 and OR: 0.51, 95%CI: 0.34-0.75), and in women with high FT (OR: 1.41, 95%CI: 1.08-1.82). Strong associations in the same direction were found with adiposity, glucose, and plasma lipid MetS components at baseline, but not with changes in these components at 2-year follow-up. The associations did not significantly differ between MDD patients and controls. CONCLUSIONS: Independently of having MDD, low testosterone levels in men and, in contrast, high testosterone levels in women were significantly associated with MetS and its components.

Differences in Speed of Response of Depressive Symptom Dimensions in Older Persons During Electroconvulsive Therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is an important and effective treatment for depression. However, research on course trajectories of depressive symptoms during ECT is limited. Insight into putative differences in speed of response of depressive symptom dimensions may enable clinicians to optimally inform patients and their relatives. Therefore, we aim to examine course trajectories of depressive symptom dimensions in depressed older persons during ECT. METHODS: Data were derived from the Mood Disorders in Elderly treated with Electro Convulsive Therapy study, including 110 persons, aged 55 years or more, with a current diagnosis of major depressive disorder and referred for ECT. Exploratory factor analysis was used to identify symptom dimensions, using the 10 depression items of the Montgomery-Åsberg Depression Rating Scale (MADRS). Differences in course trajectories of symptom dimension during 2 weeks were examined by multilevel analyses. RESULTS: Three symptom dimensions were identified: a "mood," "melancholic," and "suicidal" dimension. Mood showed a significantly greater severity decline as compared with melancholic and suicidal at the 1-week follow-up. At the 2-week follow-up, both mood and melancholic demonstrated a significantly greater decline as compared with suicidal. However, because scores on the suicidality item of the Montgomery-Asberg Depression Rating Scale were already lower at baseline compared with the other items, a floor effect cannot be ruled out. DISCUSSION: All symptom dimensions of depression showed a rapid response to ECT. Our findings did not support the general assumption that suicidal symptoms may be the first to improve. However, a floor effect on the suicidality item cannot be ruled out.

Performance of the Psychotic Depression Assessment Scale as a Predictor of ECT Outcome.

OBJECTIVES: The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the Psychotic Depression Assessment Scale (PDAS), is a more accurate predictor. METHODS: Depression severity was assessed before and after the ECT course using the Montgomery-Asberg Depression Rating Scale (MADRS) in 31 patients with psychotic depression and 34 depressed patients without psychotic symptoms. Logistic regression models for MADRS response and remission were fitted, with either the PDAS total score or the dichotomous predictors "absence/presence of psychotic symptoms" as the independent variables. Age, episode duration, and treatment resistance were added as covariates. RESULTS: Both the asserted presence of psychotic symptoms and a higher PDAS total score reflected MADRS response (areas under the curve, 0.83 and 0.85, respectively), with MADRS remission also being predicted by the presence of psychotic symptoms and higher PDAS scores (areas under the curves, 0.86 and 0.84, respectively). Age was a contributor to these prediction models, with response and remission rates being highest in the older patients. Psychotic Depression Assessment Scale scores decreased significantly during ECT: at end point, 81.5% of the patients showed significant response and 63.9% had achieved remission. CONCLUSIONS: The PDAS indeed accurately predicts response to and remission after ECT in (psychotic) depression and most pronouncedly so in older patients but seems to have no clear advantage over simply verifying the presence of psychotic symptoms. This could be the consequence of a ceiling effect, as ECT was extremely effective in patients with psychotic depression.ClinicalTrials.gov: Identifier: NCT02562846.