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Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general populations yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m2, respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p

BackgroundHospital patient registries provide substantial longitudinal data sets describing the clinical and medical health statuses of inpatients and their pharmacological prescriptions. Despite the multiple advantages of routinely collecting multidimensional longitudinal data, those data sets are rarely suitable for advanced statistical analysis and they require customization and synthesis. ObjectiveThe aim of this study was to describe the methods used to transform and synthesize a raw, multidimensional, hospital patient registry data set into an exploitable database for the further investigation of risk profiles and predictive and survival health outcomes among polymorbid, polymedicated, older inpatients in relation to their medicine prescriptions at hospital discharge. MethodsA raw, multidimensional data set from a public hospital was extracted from the hospital registry in a CSV (.csv) file and imported into the R statistical package for cleaning, customization, and synthesis. Patients fulfilling the criteria for inclusion were home-dwelling, polymedicated, older adults with multiple chronic conditions aged ≥65 who became hospitalized. The patient data set covered 140 variables from 20,422 hospitalizations of polymedicated, home-dwelling older adults from 2015 to 2018. Each variable, according to type, was explored and computed to describe distributions, missing values, and associations. Different clustering methods, expert opinion, recoding, and missing-value techniques were used to customize and synthesize these multidimensional data sets. ResultsSociodemographic data showed no missing values. Average age, hospital length of stay, and frequency of hospitalization were computed. Discharge details were recoded and summarized. Clinical data were cleaned up and best practices for managing missing values were applied. Seven clusters of medical diagnoses, surgical interventions, somatic, cognitive, and medicines data were extracted using empirical and statistical best practices, with each presenting the health status of the patients included in it as accurately as possible. Medical, comorbidity, and drug data were recoded and summarized. ConclusionsA cleaner, better-structured data set was obtained, combining empirical and best-practice statistical approaches. The overall strategy delivered an exploitable, population-based database suitable for an advanced analysis of the descriptive, predictive, and survival statistics relating to polymedicated, home-dwelling older adults admitted as inpatients. More research is needed to develop best practices for customizing and synthesizing large, multidimensional, population-based registries. International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2019-030030

Abstract Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population’s yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m2, respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p

Abstract Background Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer’s disease (AD) pathology and cognitive decline. Methods One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. Results None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). Conclusion Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.

IntroductionMajor depressive disorder (MDD) exhibits heterogeneity in treatment response.ObjectiveThis exploratory analysis aims to evaluate the differential changes in individual items of the MADRS between melancholic MDD (M-MDD) and unspecified MDD (U-MDD) following electroconvulsive therapy (ECT).MethodsThe study included 23 patients with unipolar MDD who received ECT. Patients were classified as M-MDD or U-MDD according to DSM-5 criteria. MADRS scores were assessed at baseline and one-month post-ECT. Differences between subtypes were analyzed using the Wilcoxon test and multiple linear regression.ResultsAmong 23 participants receiving ECT for MDD, 10 had M-MDD and 13 had U-MDD. Baseline MADRS items showed significantly higher scores in the M-MDD group, except for reported sadness, suicidal ideation, and concentration difficulties. Total MADRS score reduction was significantly greater in the M-MDD group. This decline was especially pronounced in M-MDD patients for specific items, including apparent sadness, inability to feel, pessimistic thoughts, sleep disturbances, reduced appetite, and concentration difficulties, after adjusting for age and sex.ConclusionMADRS score reductions were more substantial for M-MDD than U-MDD in both total and specific items following one month of ECT. Further research with larger samples is needed to clarify MADRS response differences after ECT between melancholic and unspecified depressive subtypes.

BackgroundDepression is a highly prevalent psychopathological condition among older adults, particularly those institutionalized in nursing homes (NHs). Unfortunately, it is poorly identified and diagnosed. NH residents are twice as likely to fall as community-dwelling older adults. There is a need for more knowledge about the mechanisms and relationships between depression and falls. ObjectiveThis study aims to identify, analyze, and synthesize research on the relationships between depression and falls among NH residents. MethodsA literature search was conducted in October 2023 in the following bibliographic databases: MEDLINE ALL Ovid, Embase, CINAHL with Full Text EBSCO, APA PsycInfo Ovid, Web of Science Core Collection, the Cochrane Database of Systematic Reviews Wiley, and ProQuest Dissertations & Theses A&I. Clinical trials were searched for in the Cochrane Central Register of Controlled Trials Wiley, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. Additional searches were performed using Google Scholar, the DART-Europe E-theses Portal, and backward citation tracking. The Newcastle-Ottawa Scale and the Appraisal tool for Cross-Sectional Studies were used to evaluate study quality. ResultsThe review included 7 quantitative studies published in 7 different countries from 3 continents; of these, 6 (86%) were cross-sectional studies, and 1 (14%) was a prospective cohort study. Results suggested high frequencies of depressive symptoms and falls among older adults living in NHs, and depressive symptoms were considered a risk factor for falls. The 15-item and 10-item versions of the Geriatric Depression Scale were the most commonly used measurement tools, followed by the Cornell Scale for Depression in Dementia and the Resident Assessment Instrument-Minimum Data Set 2.0. The prevalence of depression was heterogeneous, varying from 21.5% to 47.7% of NH residents. The studies used heterogeneous descriptions of a fall, and some considered the risk of falls, recurrent fallers, and near falls in their data. The prevalence of fallers was disparate, varying from 17.2% to 63.1%. Of the 7 retained studies, 6 (86%) reported a relationship between depression and falls or the risk of falls. Among the 19 other risk factors identified in the review as being associated with falls among NH residents were a history of falls in the last 180 days, >1 fall in the past 12 months, and respiratory illnesses. ConclusionsThere is a paucity of research examining falls among older adults with depressive symptoms in NHs. These findings should alert nurses to the need to consider depression as a risk factor in their work to prevent falls. More research is needed to gain a comprehensive understanding of fall risk among NH residents with depressive symptoms. International Registered Report Identifier (IRRID)RR2-10.2196/46995

Electroconvulsive therapy is an effective and well-tolerated antidepressant treatment for the elderly population. The place of electroconvulsive therapy in the treatment sequence for depression in the elderly is currently not well established. This review aims to identify the factors that contribute to a positive response and remission in elderly patients with depression undergoing electroconvulsive therapy treatment. We searched five bibliographic databases (Medline ALL Ovid, Embase.com, APA PsycInfo Ovid, Cochrane Library Wiley and Web of Science Core Collection) for articles published between 1995 and June 2023. Of the 2149 articles screened, 19 were included in the review. No significant associations were found between remission and/or response and salivary cortisol, baseline hippocampal and white matter hyperintensities, total amyloid load or global cortical atrophy. The reviewed articles did not show a significant difference in remission between unilateral and bilateral electroconvulsive therapy treatment. Other interesting findings are that moderately elevated levels of CRP and S100B levels, lower retardation scores, poorer performance on the word reading task at baseline and longer post-ictal reorientation time may be associated with higher remission and/or response rates. Medial temporal atrophy can be associated with lower Montgomery-Åsberg Depression Rating Scale (MADRS) decrease after electroconvulsive therapy. Finally, elderly patients had higher rates of electroconvulsive therapy response; retardation and psychotic features may mediate this association. Incorporation of this data into clinical practice may facilitate a personalised approach to electroconvulsive therapy. However, research on this topic is scarce and there are few studies that focus specifically on older people.

BackgroundFrailty is a widespread geriatric syndrome among older adults, including hospitalized older inpatients. Some countries use electronic frailty measurement tools to identify frailty at the primary care level, but this method has rarely been investigated during hospitalization in acute care hospitals. An electronic frailty measurement instrument based on population-based hospital electronic health records could effectively detect frailty, frailty-related problems, and complications as well be a clinical alert. Identifying frailty among older adults using existing patient health data would greatly aid the management and support of frailty identification and could provide a valuable public health instrument without additional costs. ObjectiveWe aim to explore a data-driven frailty measurement instrument for older adult inpatients using data routinely collected at hospital admission and discharge. MethodsA retrospective electronic patient register study included inpatients aged ≥65 years admitted to and discharged from a public hospital between 2015 and 2017. A dataset of 53,690 hospitalizations was used to customize this data-driven frailty measurement instrument inspired by the Edmonton Frailty Scale developed by Rolfson et al. A 2-step hierarchical cluster procedure was applied to compute e-Frail-CH (Switzerland) scores at hospital admission and discharge. Prevalence, central tendency, comparative, and validation statistics were computed. ResultsMean patient age at admission was 78.4 (SD 7.9) years, with more women admitted (28,018/53,690, 52.18%) than men (25,672/53,690, 47.81%). Our 2-step hierarchical clustering approach computed 46,743 inputs of hospital admissions and 47,361 for discharges. Clustering solutions scored from 0.5 to 0.8 on a scale from 0 to 1. Patients considered frail comprised 42.02% (n=19,643) of admissions and 48.23% (n=22,845) of discharges. Within e-Frail-CH’s 0-12 range, a score ≥6 indicated frailty. We found a statistically significant mean e-Frail-CH score change between hospital admission (5.3, SD 2.6) and discharge (5.75, SD 2.7; P

Abstract Background Despite most centenarians facing age-related declines in functional and cognitive capacities, the severity of these declines varies among individuals, as does the maintenance of good mental health (e.g., depressive symptoms) despite these declines. This study aims to examine this heterogeneity in centenarians from the Second Heidelberg Centenarian Study, which collected data from 112 centenarians living in Germany. In our study, we focus on a subsample of 73 centenarians who provided self-reports for our measures of interest (M age = 100.4, SD age = 0.55). Methods We examined correlations between functional capacity (i.e., PADL, IADL), cognitive capacity (i.e., MMSE), and depressive symptoms (i.e., GDS), and the existence of different profiles using hierarchical clustering. Results Higher functional capacity was related to higher cognitive capacity and to fewer depressive symptoms. Yet, higher cognitive capacity was associated with more depressive symptoms. Hierarchical clustering analysis elucidated this contradiction by identifying three profiles: low-capacity individuals (i.e., 24 individuals had low functional and cognitive capacities, with low depressive symptoms), high-capacity individuals (i.e., 33 individuals with high functional and cognitive capacities, with low depressive symptoms), and low-functional-high-cognitive-capacity individuals (i.e., 16 individuals showed low functional but high cognitive capacity, with high depressive symptoms). Our post-hoc analyses highlighted arthritis and pain as risk factors for functional dependence and depression. Conclusions Our findings emphasize the importance of identifying centenarian subgroups with specific resource- and risk profiles to better address their needs, and of treating pain to improve functional capacity and mental health in centenarians.

Abstract Background Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. Results A global methylation increase was noted after the first month of treatment, which was more pronounced (p

Mismatch repair-deficient (dMMR) prostate cancer (PCa) is a rare (1–5%) but highly actionable molecular subgroup of PCa, vulnerable to immune checkpoint inhibitors. Our case of sporadic dMMR PCa due to large monoallelic co-deletion of EPCAM, MSH2, and MSH6 features a clinically aggressive disease presentation and a major response to pembrolizumab. We report a 65-year-old patient with primary metastatic PCa, Gleason score 5 + 5 = 10, with penile and lymph node metastases at diagnosis. Patient showed rapid progression on first-line ADT and enzalutamide. Tumor next-generation sequencing (NGS) revealed microsatellite instability and a tumor mutational burden of 40.8 mutations/megabase. Immunohistochemistry showed co-loss of MSH2 and MSH6. Review of NGS row data confirmed large monoallelic deletion in chromosome 2p, including EPCAM, MSH2, and MSH6. No germline alterations in mismatch repair genes were detected. Patient showed excellent response to pembrolizumab, which is still ongoing. We conclude that early molecular tumor profiling is essential to enable personalized management of advanced PCa, especially in patients with aggressive or atypical disease course.

Completion of an advance care planning (ACP) process and/or an advance directive should result in patients receiving the care they desire at the end of life. However, three decades of research have shown that is just not the case. ACP has been a front runner in developing the science within palliative care. Some positive outcomes such as lowering levels of surrogate grief may be associated with ACP. Yet, it does not appear that further ACP research will ensure that seriously ill patients will get goal-concordant care. An unfortunate consequence of palliative care research and advocacy so far is the misguided notion of many hospital systems trying to solve their palliative care problems by only implementing an ACP initiative. At best, ACP is but one tool in the collective palliative care toolbox. New tools are needed. Given that we have finite resources, future research should focus more on tools to improve symptom management, better models of care, and systems that will ensure goal-concordant care that meet the needs of the population that the health care system is designed to meet.

Abstract Background Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing. Methods Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall. Results Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles.Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment.Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03–1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02–1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04–1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04–1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment.Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

Objective: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. Design: Secondary analysis of a prospective population-based cohort study. Participants: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. Measurements: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. Methods: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. Results: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (−3% to 26.5%)] and eggs [18% (2.3%–33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. Conclusion: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results.

BackgroundPsychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.MethodsBetween 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.ResultsA total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.ConclusionThe observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

Summary: Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere to neurodegeneration and cognitive decline, and have cholesterol-lowering, anti-inflammatory, and antioxidant qualities. Here, we investigated the potential associations between circulating cholesterol precursors and metabolites, triglycerides, and phytosterols with cognitive decline in older people by performing multivariate analysis on 246 participants engaged in a population-based prospective study. In our analysis we considered the potential effect of sex and APOEe4. We reveal particular dysregulations of diet-derived phytosterols and endogenous cholesterol synthesis and metabolism, and their variations over time linked to cognitive decline in the general population. These results are significant to the development of interventions to avoid cognitive decline in older adults and suggest that levels of circulating sterols should be taken into account when evaluating risk.

Abstract Introduction Adverse childhood events (ACEs) have been linked to widespread chronic pain (CP) in various cross-sectional studies, mainly in clinical populations. However, the independent role of different ACEs on the development of different types of CP remains elusive. Accordingly, we aimed to prospectively assess the associations between specific types of ACEs with the development of multisite CP in a large population-based cohort. Methods Data stemmed from the three first follow-up evaluations of CoLaus|PsyCoLaus, a prospective population-based cohort study of initially 6734 participants (age range: 35–75 years). The present sample included 1537 participants with 2161 analyzable intervals (49.7% men, mean age 57.3 years). Diagnostic criteria for ACEs were elicited using semi-structured interviews and CP was assessed by self-rating questionnaires. Multinomial logistic regressions with generalized estimating equations method analyzed the relationship between the different ACEs measured in the beginning of the interval and the risk of developing multisite CP during the follow-up. Sensitivity analyses were performed to assess the predictive value of ACEs on multisite CP with neuropathic features. Results Participants with a history of parental divorce or separation had an increased risk of developing multisite CP at during follow-up in comparison to those without (RR1.98; 95% CI 1.13–3.47). A strong association was highlighted between parental divorce or separation and the risk of subsequent CP with neuropathic characteristics (RR 4.21, 95% CI 1.45–12.18). Conclusion These results highlight the importance of psychotherapeutic management of people experiencing parental separation to prevent CP in the future.

Chemical disinfectants employed in water and wastewater treatment can produce a variety of transformation products, including carbonyl compounds (e.g., saturated and unsaturated aldehydes and ketones). Experiments conducted under conditions relevant to chlorination at drinking water treatment plants and residual chlorine application in distribution systems indicate that α,β-unsaturated carbonyl compounds readily react with free chlorine and free bromine over a wide pH range but react slowly with combined chlorine (i.e., NH2Cl). For nearly all of the 11 α,β-unsaturated carbonyl compounds studied, the apparent second-order rate constants for the reaction with free chlorine increased in a linear manner with hypochlorite (OCl-) concentrations, yielding species-specific second-order rate constants for the reaction with OCl- ranging from 0.21 to 12 M-1 s-1. Predictions based on the second-order rate constants indicate that a substantial fraction (i.e., >60%) of several of the more prominent α,β-unsaturated carbonyls (e.g., acrolein, crotonaldehyde) will be transformed to an appreciable extent in distribution systems by free chlorine. Products from the reaction of chlorine with acrolein, crotonaldehyde, and methyl vinyl ketone were tentatively identified using nuclear magnetic resonance (NMR) and gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC-HRT-MS). These products lacked unsaturated carbons and, in some cases, contained multiple halogens.

BackgroundAging exposes individuals to new health disorders and debilitating chronic diseases, yet most older adults, even in functional decline, do not want to leave their homes. Nevertheless, for many, institutionalization in a nursing home (NH) may become essential to ensure their continued safety and health. Depression is one of the most common psychiatric disorders among older adults, especially among those who are institutionalized. Depressed NH residents face a high risk of future functional decline and falls, decreasing their quality of life. The relationship between depression and falls is complex and bidirectional. Previous reviews have focused on home-dwelling older adults or explored the relationship between antidepressant drugs and falls. To the best of our knowledge, no integrative literature reviews have explored the relationship between depression and falls among NH residents. ObjectiveAnalyze studies on the relationship between depression and falls among NH residents. MethodsWe will conduct an integrative literature review of published articles in relevant scientific journals on the relationship between depression and depressive symptomatology and falls among NH residents. As usually defined, we will consider NH residents to be people aged 65 years and older who can no longer live safely and independently in their homes. We will also consider older adults on short-term stays in an NH for rehabilitation after hospital discharge. Retrieved articles will be screened for eligibility and analyzed following previously reported steps. The most pertinent bibliographical databases will be examined for qualitative, quantitative, and mixed methods studies, from inception until August 31, 2023, thus ensuring that all relevant literature is included. We will also hand-search the bibliographies of all the relevant articles found and search for unpublished studies in any language. If appropriate, we will consider conducting a meta-analysis of the studies retrieved. ResultsA first round of data collection was completed in March 2023. We retrieved a total of 2276 references. A supplementary literature search to ensure the most up-to-date evidence is ongoing. We anticipate that the review will be completed in late September 2023, and we expect to publish results at the end of December 2023. ConclusionsThis integrative review will increase knowledge and understanding of the complex relationship between depression and falls in NH environments. Its findings will be important for developing integrated, multidisciplinary models and care recommendations, adaptable to each NH resident’s situation and health status, and for creating preventive interventions to help them maintain or recover optimal health stability. International Registered Report Identifier (IRRID)DERR1-10.2196/46995

Despite decades of research on the fate of phenolic compounds when water is disinfected with hypochlorous acid (HOCl), there is still considerable uncertainty regarding the formation mechanisms and identity of ring cleavage products, especially at higher chlorine doses. This study focuses on the formation of electrophilic ring cleavage products-a class of compounds that poses potential health risks at relatively low concentrations-from the reactions of phenols with chlorine. By monitoring the formation of products of reactions between ring cleavage products and the model nucleophile N-α-acetyl-lysine, we identified the α,β-unsaturated dialdehyde 2-butene-1,4-dial (BDA) and its chlorinated analogue, chloro-2-butene-1,4-dial (Cl-BDA), after the chlorination of phenol, para- and ortho-substituted chlorophenols (2-Cl, 4-Cl, 2,4-diCl-, 2,6-diCl, and 2,4,6-triCl-phenol), and 3,5-di-Cl-catechol. Maximum yields of BDA were observed when chlorine was present in large excess (HOCl/phenol ratios of 30:1 to 50:1), with yields ranging from 18% for phenol to 46% for 3,5-diCl-catechol. BDA and Cl-BDA formation was also observed during the chlorination of brominated phenols. For methyl-substituted phenols, the presence of methyl substituents in both positions ortho to the hydroxy group inhibited BDA and Cl-BDA formation, but the chlorination of cresols and 2,3-dimethylphenol yielded methyl- and dimethyl-BDA species. This study provides new insights into the formation of reactive and toxic electrophiles during chlorine disinfection. It also provides evidence for the importance of phenoxy radicals produced by one-electron transfer reactions initiated by chlorine in the production of dicarbonyl ring cleavage products.