TEMPUS, a Timepix4-based system for the event-based detection of X-rays.

TEMPUS is a new detector system being developed for photon science. It is based on the Timepix4 chip and, thus, it can be operated in two distinct modes: a photon-counting mode, which allows for conventional full-frame readout at rates up to 40 kfps; and an event-driven time-stamping mode, which allows excellent time resolution in the nanosecond regime in measurements with moderate X-ray flux. In this paper, the initial prototype, a single-chip device, is introduced, and the readout system described. Moreover, and in order to evaluate its capabilities, some tests were performed at PETRA III and ESRF for which results are also presented.

Rational Pharmacotherapy in Type 2 Diabetes: Danish Data From 2002 to 2020 on Mortality, Diabetes- Related Outcomes, Adverse Events, and Medication Expenses.

OBJECTIVE: Developments in pharmacotherapy and management of type 2 diabetes may have shifted the balance of treatment benefits versus harms and costs over the past decades. This study aimed to describe the trends in this balance. RESEARCH DESIGN AND METHODS: We followed the Danish population with type 2 diabetes between 2002 and 2020, analyzing their medication use in relation to treatment benefits (such as mortality and diabetes-related outcomes), adverse events, and medication costs. Using multivariate analyses, we adjusted for potential confounders, including age, sex, and socioeconomic status. RESULTS: The study included 461,805 individuals. From 2002 to 2020, the median age increased from 66 to 68 years, and the mean number of comorbidities increased from 5.2 to 8.8. The overall incidence of cardiovascular, renal, and other important adverse clinical outcomes decreased. Similarly, the rate of some adverse events, such as gastric bleeding, hypoglycemia, and falls declined, whereas the incidence of electrolyte imbalances and ketoacidosis increased. The average per-patient cost was reduced by 8%, but total medication expenses increased by 148% due to an expanding population size, lowered costs of most cardiovascular medications, and increasing costs for glucose-lowering drugs. CONCLUSIONS: Advancements in type 2 diabetes management have led to reduced risk of both diabetes-related outcomes and treatment harms, while maintaining relatively stable per-patient medication expenses. Although these trends are multifactorial, they suggest more rational pharmacotherapy. Still, increased risk of certain adverse events, along with increasing costs for glucose-lowering medications, underscores the need for ongoing vigilance and risk-benefit analysis.

Increasing Medication Use and Polypharmacy in Type 2 Diabetes: The Danish Experience From 2000 to 2020.

OBJECTIVE: Type 2 diabetes often coexists with other conditions that are amenable to pharmacological treatment. We hypothesized that polypharmacy among individuals with type 2 diabetes has increased since 2000. RESEARCH DESIGN AND METHODS: Using Danish national registries, we established a cohort of all Danish individuals (aged ≥18 years) with type 2 diabetes between 2000 and 2020. We analyzed their medication use and prevalence of varying degrees of polypharmacy (≥5 or ≥10 medications), stratifying by age, sex, number of chronic diseases, and socioeconomic status. RESULTS: The cohort grew from 84,917 patients in 2000 to 307,011 in 2020, totaling 461,849 unique patients. The number of daily medications used per patient increased from (mean ± SD) 3.7 ± 2.8 (in 2000) to 5.3 ± 3.2 (in 2020). The lifetime risk of polypharmacy was substantial, with 89% (n = 409,062 of 461,849) being exposed to ≥5 medications at some point and 47% (n = 217,467of 461,849) to ≥10 medications. The increases were driven by an expanding group of medications, with analgesics, antihypertensives, proton pump inhibitors, and statins having the largest net increase. Advanced age, male sex, lower socioeconomic status, and Danish ethnicity positively correlated with polypharmacy but could not explain the overall increase in polypharmacy. CONCLUSIONS: Medication use and polypharmacy have increased among patients with type 2 diabetes. Although the implications and appropriateness of this increased medication use are uncertain, the results stress the increasing need for health care personnel to understand the potential risks associated with polypharmacy, including medication interactions, adverse effects, and over- and underprescribing.

Natural IgG protects against early dissemination of vesicular stomatitis virus.

Neonatal Fc receptor (FcRn) recycles immunoglobulin G, and inhibition of FcRn is used clinically for treatment of autoimmune diseases. In this work, using the vesicular stomatitis virus (VSV) mouse infection model system, we determined the role of FcRn during virus infection. While induction of neutralizing antibodies and long-term protection of these antibodies was hardly affected in FcRn deficient mice, FcRn deficiency limited the amount of natural IgG (VSV-specific) antibodies. Lack of natural antibodies (nAbs) limited early control of VSV in macrophages, accelerated propagation of virus in several organs, led to the spread of VSV to the neural tissue resulting in fatal outcomes. Adoptive transfer of natural IgG into FcRn deficient mice limited early propagation of VSV in FcRn deficient mice and enhanced survival of FcRn knockout mice. In line with this, vaccination of FcRn mice with very low dose of VSV prior to infection similarly prevented death after infection. In conclusion we determined the importance of nAbs during VSV infection. Lack of FcRn limited nAbs and thereby enhanced the susceptibility to virus infection.

Room Temperature Phosphorescence from Natural, Organic Emitters and Their Application in Industrially Compostable Programmable Luminescent Tags.

Organic semiconductors provide the potential of biodegradable technologies, but prototypes do only rarely exist. Transparent, ultrathin programmable luminescent tags (PLTs) are presented for minimalistic yet efficient information storage that are fully made from biodegradable or at least industrially compostable, ready-to-use materials (bioPLTs). As natural emitters, the quinoline alkaloids show sufficient room temperature phosphorescence when being embedded in polymer matrices with cinchonine exhibiting superior performance. Polylactic acid provides a solution for both the matrix material and the flexible substrate. Room temperature phosphorescence can be locally controlled by the oxygen concentration in the film by using Exceval as additional oxygen blocking layers. These bioPLTs exhibit all function-defining characteristics also found in their regular nonenvironmentally degradable analogs and, additionally, provide a simplified, high-contrast readout under continuous-wave illumination as a consequence of the unique luminescence properties of the natural emitter cinchonine. Limitations for flexible devices arise from limited thermal stability of the polylactic acid foil used as substrate allowing only for one writing cycle and preventing an annealing step during fabrication. Few-cycle reprogramming is possible when using the architecture of the bioPLTs on regular quartz substrates. This work realizes the versatile platform of PLTs with less harmful materials offering more sustainable use in future.

Effects of Different Types of Intermittent Fasting Interventions on Metabolic Health in Healthy Individuals (EDIF): A Randomised Trial with a Controlled-Run in Phase.

The effects of intermittent fasting (IF) on health promotion in the healthy population remain controversial. Therefore, our study aimed to analyse the efficacy and feasibility of different IF protocols and evaluated the effects within a cohort with a controlled-run in phase on the body mass index (BMI) as the primary outcome, the body composition, and metabolic and haematological markers in healthy participants. A total of 25 individuals were randomised into three fasting groups: 16/8 fasting (n = 11), 20/4 fasting (n = 6), and alternate-day fasting (ADF, n = 8). Assessments were conducted at baseline (visit 1), after a four-week controlled-run in phase (visit 2), and after eight weeks of fasting (visit 3). Both the BMI (p = 0.01) and bodyweight (p = 0.01) were significantly reduced in the ADF group, which was not seen in the 16/8 and 20/4 groups (p > 0.05). Adherence was different but not statistically among the groups (16/8: 84.5 ± 23.0%; 20/4: 92.7 ± 9.5%; and ADF: 78.1 ± 33.5%, p = 0.57). Based on our obtained results, the data suggest that some fasting interventions might be promising for metabolic health. However, adherence to the specific fasting protocols remains challenging even for the healthy population.

No Effect of Serum Electrolyte Levels on Electroconvulsive Therapy Seizure Quality Parameters.

INTRODUCTION: Seizure quality is considered to be associated with treatment outcomes of electroconvulsive therapy (ECT). A wide range of treatment parameters and patient characteristics are known to influence seizure quality. However, conflicting results exist for the role of serum electrolyte levels and seizure quality. METHODS: We retrospectively analyzed a total of 454 patients and a total of 2119 individual acute ECT sessions irrespective of diagnosis where a clinical evaluation of serum levels of sodium, potassium, and calcium took place routinely up to 2 days before the ECT session. To assess the impact of serum electrolyte levels on seizure quality parameters, we used mixed-effects linear regression analysis with Bonferroni correction for multiple testing. RESULTS: Serum sodium, potassium, and calcium levels were not associated with seizure quality markers after correcting the significance level for multiple testing. Younger age was consistently associated with higher postictal suppression, interhemispheric coherence, midictal amplitude, and peak heart rate. Lower dose was consistently associated with longer electroencephalogram and motor seizure duration. CONCLUSIONS: Our results suggest that there is no clinically relevant effect of serum electrolyte levels on seizure quality, at least within clinically commonly observed ranges of serum electrolyte concentrations.

Sustainable space technologies-Strategies toward a predictive aerothermal design of re-useable space transportation systems.

This paper presents a review of current aerothermal design and analysis methodologies for spacecraft. It briefly introduces the most important system architectures, including rockets, gliders, and capsule-based configurations, and gives an overview of the specific aerothermal and thermo-chemical effects that are encountered during their different flight phases and trajectories. Numerical and experimental design tools of different fidelity levels are reviewed and discussed, with a specific focus placed on the present limitations and uncertainty sources of models for the wide range of physical phenomena that are encountered in the analyses. This includes high temperature thermodynamics, chemical effects, turbulence, radiation, and gasdynamic effects. This is followed by a summary of current predictive capabilities and research foci, with missing capabilities identified. Finally, a future strategy toward an efficient and predictive aerothermal design of re-useable space transportation systems is proposed.

Cerebral and Aortic Aneurysms in Electroconvulsive Therapy Patients: A Systematic Review and Results From 12 Years of Screening.

INTRODUCTION: Theoretically, the procedural risk of electroconvulsive therapy (ECT) could be increased in the presence of undetected aneurysms due to the hemodynamic changes associated with ECT. However, empirical evidence is limited to few individual case reports and case series. METHODS: We performed a systematic review of available evidence on ECT treatment in patients with intracranial aneurysms and untreated aortic aneurysms and we retrospectively analyzed data from 252 consecutive patients referred for ECT at the Department of Psychiatry, Psychotherapy and Psychosomatics of Siegen Hospital, Germany, who received magnetic resonance angiographies and abdominal sonographies as part of their routine pre-ECT workup. RESULTS: Of 252 patients referred for ECT, 5 (2.0%) were found to have an intracerebral aneurysm and 1 (0.4%) was found to have an abdominal aortic aneurysm. These cases are reported in detail together with 2 additional cases of aortic aneurysms from the Central Institute of Mental Health, Mannheim, Germany. Electroconvulsive therapy was performed without complications in all 8 cases. CONCLUSIONS: Aneurysms might occur in ECT patients at a similar rate as in the general population. The number of ECTs performed annually in mostly unscreened patients suggests that there might be a significant number of patients with undetected aneurysms in whom ECT is performed without reported complications.

Catatonia and ECT across the lifespan.

Electroconvulsive therapy (ECT) is a safe and effective treatment for catatonia with high response rates. Although empirical data suggest that tolerability and efficacy are at least as good as in adults, ECT treatment of children, adolescents, and geriatric patients seems to pose a specific challenge for many practitioners. This article intends to explore and discuss reasons hindering the use of ECT in these patient groups, give an overview on the use of ECT to treat catatonia and provide practical advice on ECT in children, adolescents, and geriatric patients for the treatment of catatonia. Classification of catatonia as a subform of schizophrenia and a diagnostic overlap with other common conditions in children, adolescents, and geriatric patients might lead to underdiagnosis of catatonia. Concerns about the mechanism of action and about a lack of controlled studies as well as general concerns about the use of ECT in children and adolescents might lead to underutilization of ECT. However, studies of ECT to treat catatonia in children, adolescents, and geriatric patients consistently show its safety and effectiveness. Administration of ECT needs to consider some specific characteristics of children, adolescents, and geriatric patients. In conclusion, ECT is a safe and highly effective treatment for catatonia across the lifespan. Existing evidence does not warrant restrictions of its use in certain age groups.

Age disparities in glucose-lowering treatment for Danish people with type 2 diabetes: a cross-sectional study between 2019 and 2020.

BACKGROUND: The pharmacotherapeutic guidelines for type 2 diabetes have changed considerably during the past decades. SGLT2 inhibitors and GLP-1 receptor agonists have emerged as first-line agents by preventing cardiovascular events within a few years of treatment. In contrast, sulphonylureas and insulin have been deprioritised due to less beneficial effects and the risk of hypoglycaemia-particularly in older people who are frail. We hypothesised that medications with a high risk of hypoglycaemia were used more often in older people compared with younger people. METHODS: In a nationwide cohort of people with type 2 diabetes in Denmark from 2019 to 2020, we described the use of specific glucose-lowering medications in relation to age and glycated haemoglobin A1C (HbA1c) by descriptive statistics and regression models adjusted for sex, socioeconomic factors, renal function, and several comorbidities. FINDINGS: Among 290 890 people with type 2 diabetes, glucose-lowering medication usage peaked at age 70 years. Increasing age was associated with relatively less use of metformin, GLP-1 receptor agonists, and SGLT2 inhibitors and more use of basal insulin, DDP-4 inhibitors, and sulphonylureas. When comparing 80-year-olds with 60-year-olds at similar HbA1c levels of 6·5% (48 mmol/mol), 80-year-olds used 8% (95% CI 7-10%) fewer glucose-lowering medications, were 55% less likely to receive GLP-1 receptor agonists or SGLT2 inhibitors (relative ratio 0·45, 95% CI 0·42-0·48), and 65% more likely to receive sulphonylureas (1·65, 1·54-1·76). Among 23 032 individuals aged 80 years or older with HbA1c levels of less than 6·5% (<48 mmol/mol), 2291 (10%) used sulphonylureas or insulin. INTERPRETATION: In Danish people with type 2 diabetes, the likelihood of using glucose-lowering medications with a high risk of hypoglycaemia (eg, sulphonylureas and basal insulin) increased with age, whereas the likelihood of using GLP-1 receptor agonists and SGLT2 inhibitors decreased. Some people aged 80 years or older with an HbA1c level of less than 6·5% (48 mmol/mol) were potentially overtreated with sulphonylureas or insulin. These findings emphasise the importance of frequently re-evaluating glucose-lowering treatments. FUNDING: None. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Usp22 Deficiency Leads to Downregulation of PD-L1 and Pathological Activation of CD8+ T Cells and Causes Immunopathology in Response to Acute LCMV Infection.

Ubiquitin-specific peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, including histone H2B and transcription factors. Recently, it was reported that Usp22 acts as a negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency in acute viral infection with lymphocytic choriomeningitis virus (LCMV). We found that the lack of Usp22 on bone marrow-derived cells (Usp22fl/fl Vav1-Cre mice) reduced the induction of type I and II interferons. A limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22-deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

Methodological Considerations for Describing Medication Changes in Relation to Clinical Events and Death: An Applied Example in Patients with Type 2 Diabetes and Cancer.

INTRODUCTION: Certain clinical events reduce life expectancy and necessitate a reassessment of patient treatment. OBJECTIVE: To describe medication changes in relation to a cancer diagnosis and the end of life and to highlight challenges and limitations with such descriptions. METHODS: From a cohort with all Danish patients with type 2 diabetes, we matched patients with incident cancer during 2000-2021 (n = 41,745) with patients without cancer (n = 166,994) using propensity scores. We described their medication usage from cancer diagnosis until death. RESULTS: The 1- and 5-year mortality were 51% and 86%, respectively, in the cancer group, and 13% and 59% in the non-cancer group. In relation to cancer diagnosis and death, the use of symptomatic medications (e.g., opioids, benzodiazepines) increased (10-60 incident medications per 100 patient-months), and the use of preventive medications (e.g., antihypertensives, statins) decreased (5-30% fewer users). The changes in relation to the diagnosis were driven by patients with short observed lengths of survival (< 2 years). In contrast, changes occurring within a year before death were less dependent on survival strata, and > 60% used preventive medications in their last months. CONCLUSIONS: Medication changes in relation to a cancer diagnosis were frequent and correlated to the length of survival. The results showcase the challenges and limited clinical utility of anchoring analyses on events or death. While the former diluted the results by averaging changes across patients with vastly different clinical courses, the latter leveraged information unavailable to the treating clinicians. While medication changes were common near death, preventive medications were often used until death.

[Climate change, biodiversity loss and pollution: consequences for psychiatry]. / Klimawandel, Biodiversitätsverlust und Verschmutzung: Folgen für die Psychiatrie.

The climate crisis, loss of biodiversity and increasing global pollution are a threat to mental health. Comprehensive transformations are needed to overcome these crises, which will also affect the mental healthcare system. If done correctly these change processes can seize the chance to improve mental health while at the same time addressing the crises. This includes avoiding the need for psychiatric treatment by strengthening the focus on mental health promotion and prevention, and also considering environmental aspects when targetting therapy procedures. In addition, by focusing on nutrition, mobility and the effects of nature, patients can be empowered to increase their mental resilience whilst reducing the negative effects on the environment. At the same time, the mental healthcare system must adapt to changing environmental conditions: increasing heat waves make protective measures necessary, especially for people with mental illnesses and increasing extreme weather events can lead to shifts in the spectrum of illnesses. Appropriate funding mechanisms will have to be established to support mental healthcare throughout this transformation.

Expression of Interferon Regulatory Factor 8 (IRF8) and Its Association with Infections in Dialysis Patients.

Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC p < 0.001, mDC1 p < 0.001, mDC2 p = 0.005) and increased numbers of IRF8-positive monocytes (p < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections (p = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.

Medication changes implemented during medication reviews and factors related to deprescribing: Posthoc analyses of a randomized clinical trial in geriatric outpatients with polypharmacy.

AIMS: To provide posthoc analyses of a clinical trial that reported beneficial effects of medication reviews on health-related quality of life. Specifically, to describe the medication changes with a focus on deprescribing and to explore patient- and medication-related factors that may identify patients most likely to benefit from medication reviews. METHODS: Posthoc analyses of data from a pragmatic, nonblinded, randomized clinical trial investigating a medication review intervention (NCT03911934) in 408 geriatric outpatients treated with ≥9 medicines. RESULTS: In the medication review group (n = 196), 26% of the medicines prescribed at baseline were discontinued with 82% still being discontinued after 13 months. The most common reason for discontinuation was lack of indication (72% of discontinuations). The medicines most often discontinued in the medication review group compared with usual care included: metoclopramide (11/15 = 73% discontinued vs. 1/12 = 8% in usual care), acetylsalicylic acid (20/48 = 42% vs. 2/47 = 4%), simvastatin (18/48 = 38% vs. 2/58 = 3%), zopiclone (23/59 = 39% vs. 4/54 = 7%), quinine (9/14 = 64% vs. 6/16 = 38%), citalopram (4/18 = 22% vs. 0/20 = 0%) and tramadol (18/37 = 49% vs. 8/30 = 27%). Factors associated with number of deprescribed medicines included: number of prescribed medicines, Drug Burden Index, patient motivation for medicine changes, and prescriptions of metoclopramide, iron preparations, antidepressants other than selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, or drugs for urinary incontinence. CONCLUSION: Physician-led medication reviews resulted in persistent deprescribing of medicines in older polypharmacy patients treated with ≥9 medicines. Motivation for having their medicine changed, treatment with more medicines, and a higher burden of sedative and anticholinergic medicines characterized the patients most likely to benefit from physician-led medication reviews.

Imaging via Correlation of X-Ray Fluorescence Photons.

We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecond-duration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters. Since fluorescence can dominate coherent scattering, this may enable imaging uncrystallised macromolecules.

Evolution of Length-Dependent Properties of Discrete n-Type Oligomers Prepared via Scalable Direct Arylation.

Efficient organic electronic devices are fabricated from both small molecules and disperse polymers, but materials with characteristics in between remain largely unexplored. Here, we present a gram-scale synthesis for a series of discrete n-type oligomers comprising alternating naphthalene diimide (NDI) and bithiophene (T2). Using C-H activation, discrete oligomers of type T2-(NDI-T2)n (n ≤ 7) and persistence lengths up to ∼10 nm are made. The absence of protection/deprotection reactions and the mechanistic nature of Pd-catalyzed C-H activation allow one to produce symmetrically terminated species almost exclusively, which is key to the fast preparation, high yields, and the general success of the reaction pathway. The reaction scope includes different thiophene-based monomers, end-capping to yield NDI-(T2-NDI)n (n ≤ 8), and branching at T2 units by nonselective C-H activation under certain conditions. We show how the optical, electronic, thermal, and structural properties depend on oligomer length along with a comparison to the disperse, polymeric analogue PNDIT2. From theory and experiments, we find that the molecular energy levels are not affected by chain length resulting from the strong donor-acceptor system. Absorption maxima saturate for n = 4 in vacuum and for n = 8 in solution. Linear oligomers T2-(NDI-T2)n are highly crystalline with large melting enthalpies up to 33 J/g; NDI-terminated oligomers show reduced crystallinity, stronger supercooling, and more phase transitions. Branched oligomers and those with bulky thiophene comonomers are amorphous. Large oligomers exhibit similar packing characteristics compared to PNDIT2, making these oligomers ideal models to study length-structure-function relationships at constant energy levels.

Effects of Different Fasting Interventions on Cardiac Autonomic Modulation in Healthy Individuals: A Secondary Outcome Analysis of the EDIF Trial.

The impact of a fasting intervention on electrocardiographic (ECG) time intervals and heart rate variability (HRV) is a focus that is scarcely analyzed. The main focus of these secondary outcome data was to describe the impact of a different fasting intervention on ECG and HRV analyses. Twenty-seven healthy individuals participated in this study (11 females, aged 26.3 ± 3.8 years, BMI 24.7 ± 3.4 kg/m2), including a pre-intervention controlled run-in period. Participants were randomized to one of the three fasting cohorts: (I) alternate day fasting (ADF, n = 8), (II) 16/8 fasting (16/8 h of fasting/feasting, n = 11) and (III) 20/4 fasting (20/4 h of fasting/feasting, n = 8). An analysis of baseline ECG parameters and HRV parameters following different fasting interventions demonstrated the safety of these interventions without impacting on heart rate variability parameters during Schellong-1 testing, and revealed comparable preserved autonomic cardiac modulation (ACM) independently of the fasting intervention. In conclusion, different short-term fasting interventions demonstrated no safety ECG-based concerns and showed comparable ACM based on ECG and HRV assessments. Finally, our research topic might strengthen the scientific knowledge of intermittent fasting strategies and indicate potential clinically preventive approaches with respect to occurring metabolic disease and obesity in healthy young subjects.

Age-Dependent Dose Increase During an Acute Electroconvulsive Therapy Series.

INTRODUCTION: Electroconvulsive therapy (ECT) dose is highly relevant for ECT efficacy as well as adverse effects. It is often based on seizure threshold (ST). Studies have shown that ST increases over the course of an ECT series. Clinical observation suggests that this rise might be more pronounced in geriatric patients. METHODS: Retrospectively, we analyzed ECT dose during the first 20 ECT treatments in 472 patients undergoing ECT. Dose adjustments were assessed in relation to patients' age using generalized least squares regression analysis. Response was defined as Clinical Global Impression Improvement Scale < 4. RESULTS: Dose increased in all patients during the course of the ECT series (mean initial dose, 64.97 ± 68.04 mC; at 10th ECT, 385.46 ± 211.28 mC). Dose was significantly correlated with ECT treatment number, electrode placement, and the interaction between age and ECT treatment number. In other words, dose increase was significantly positively correlated with increasing age, that is dose increased more in older compared with younger patients during the course of an ECT series ( z = 9.47, P < 0.001). Response was not correlated with age-dependent dose increase; however, the length of the ECT series in responders was negatively associated with the dose increase from the first to the seventh ECT session ( F = 5.28, P = 0.0228). CONCLUSIONS: Our results indicate that ST increases more rapidly during the course of an ECT series in older compared with younger patients. To ensure high efficacy throughout the course of treatment, attention should be paid to decreasing seizure quality, especially in older patients, and dose should be adjusted accordingly.