Lifetime Course Research Articles

Alleviating the burden of depression: a simulation study on the impact of mental health services.

Depressive disorders are ranked as the single leading cause of disability worldwide. Despite immense efforts, there is no evidence of a global reduction in the disease burden in recent decades. The aim of the study was to determine the public health impact of the current service system (status quo), to quantify its effects on the depression-related disease burden and to identify the most promising strategies for improving healthcare for depression on the population level. A Markov model was developed to quantify the impact of current services for depression (including prevention, treatment and aftercare interventions) on the total disease burden and to investigate the potential of alternative scenarios (e.g., improved reach or improved treatment effectiveness). Parameter settings were derived from epidemiological information and treatment data from the literature. Based on the model parameters, 10,000,000 individual lives were simulated for each of the models, based on monthly transition rates between dichotomous health states (healthy vs. diseased). Outcome (depression-related disease burden) was operationalized as the proportion of months spent in depression. The current healthcare system alleviates about 9.5% (95% confidence interval [CI]: 9.2%-9.7%) of the total disease burden related to depression. Chronic cases cause the majority (83.2%) of depression-related burden. From a public health perspective, improving the reach of services holds the largest potential: Maximum dissemination of prevention (26.9%; CI: 26.7%-27.1%) and treatment (26.5%; CI: 26.3%-26.7%) would result in significant improvements on the population level. The results confirm an urgent need for action in healthcare for depression. Extending the reach of services is not only more promising but also probably more achievable than increasing their effectiveness. Currently, the system fails to address the prevention and treatment of chronic cases. The large proportion of the disease burden associated with chronic courses highlights the need for improved treatment policies and clinical strategies for this group (e.g., disease management and adaptive or personalized interventions). The model complements the existing literature by providing a new perspective on the depression-related disease burden and the complex interactions between healthcare services and the lifetime course.

The economic burden of autism spectrum disorder with and without intellectual disability in China: A nationwide cost-of-illness study

ObjectiveThe economic burden of autism spectrum disorder (ASD) on individuals, their families and society as a whole is poorly understood. Accurate figures are crucial for economic estimates and service planning. MethodsThe total lifetime individual costs and annual societal costs of ASD in China were estimated with a prevalence-based, gross cost of illness approach and data from multiple sources. The direct medical costs in outpatient and inpatient settings from the electronic health records (EHRs) of hospitals, and direct nonmedical costs from a national survey were included. The indirect costs were from both the national survey and the estimation using human capital methods. Age-specific lifetime incremental societal costs were measured. Comorbidity-related and unrelated costs were analyzed separately. ResultsThe discounted lifetime cost for an individual with ASD in China was $2.65 million (at 2020 prices, $) for those without intellectual disability (ID) and $4.61 million (at 2020 prices, $) for those with ID. The total cost of ASD amounted to $41.8 billion in 2020. Productivity loss were major cost drivers for ASD individuals without ID. Direct nonmedical costs (rehabilitation or adult care costs etc.) were major drivers for ASD individuals with ID. In a lifetime course, the total annual costs for middle aged and elderly (>42 years) were highest, followed by transitional adults (18–29 years) and preschoolers, both for individuals with or without ID. The distribution of costs over the lifespan varied by the cost category. ConclusionsASD imposes a substantial economic burden on families and health care systems. Sectors and services coordination should be given policy considerations.

Air pollution and cardiovascular heath in a changing climate

Air pollution and cardiovascular heath in a changing climate

Immunosuppressive drugs in renal transplantation

A kidney transplant, sometimes known as a renal transplant, is the treatment of choice for kidney failure at end stage renal disease (ESRD). The renal transplant surgery is followed by a lifetime course of immunosuppressive agents, divided into initial induction phase and later maintenance phase. It is seen that the risk of acute rejection is maximum in the initial months after transplantation (induction phase) and then reduces later (maintenance phase). In induction phase there is use of high-intensity immunosuppression immediately after transplantation, when the risk of rejection is maximum and then the dose reduced for long- term therapy. The main challenge in the renal transplantation community is long- term transplant survival. Long-term graft loss is mainly due to acute and chronic graft rejection, and also due to complications of immunosuppressive therapy. Currently, there is triple therapy as conventional immunosuppressive protocol: a calcineurin inhibitor, an antimetabolite agent, and a corticosteroid. The main aim of development of new immunosuppressive agents is not only improvement of short- term outcomes but also to increase the long- term graft survival by less nephrotoxicity, and minimal side-effects.

20-Year Prospective, Sequential Follow-Up Study of Heterogeneity in Associations of Duration of Untreated Psychosis With Symptoms, Functioning, and Quality of Life Following First-Episode Psychosis.

Determining the extent to which relationships between duration of untreated psychosis (DUP) and outcome endure longitudinally across the lifetime course of psychotic illness requires prospective, systematic studies of epidemiologically representative incidence cohorts across decades. Transience, persistence, or heterogeneity in associations between DUP and distinct outcome domains are yet to be investigated over such time frames. Prospective, sequential follow-up studies of an epidemiologically representative first-episode psychosis incidence cohort in Ireland were conducted at 6 months and 4, 8, 12, and 20 years (N=171). Linear mixed-model analyses were applied to determine whether prospective associations of DUP with symptoms, functioning, and quality of life were consistent or varied across psychotic illness trajectory over a 20-year period. Evaluations included time, DUP quartile, and DUP quartile-by-time interaction effects. Prospective, sequential follow-ups showed positive and negative symptoms, function, and quality of life to exhibit distinct trajectories of improvement in relation to shorter DUP. Despite heterogeneity in course and relationship to premorbid features, associations between shorter DUP and greater improvement were still evident 20 years after the first psychotic episode. Across the long-term course of psychotic illness, trajectories of association between shorter DUP and better outcome differed between domains of psychopathology, functionality, and quality of life. Nevertheless, such associations with shorter DUP were sustained for at least 20 years. These profiles indicate that while associations between DUP and long-term outcome can vary according to the domain of outcome, they are sustained across decades in a manner that could not be fully accounted for in terms of premorbid features or lead-time bias.

Key findings on bipolar disorders from the longitudinal FondaMental Advanced Center of Expertise-Bipolar Disorder (FACE-BD) cohort

BackgroundThe FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort. Method & resultsWe included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning. ConclusionsThe FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health.

Major Depression and Its Recurrences: Life Course Matters.

Major depression is one of the most prevalent and debilitating personal and public health conditions worldwide. Less appreciated is that depression's tremendous burdens are not shared equally among all who become depressed. Some will suffer recurrences over the rest of their lives, whereas half or more will never have a recurrence. Based on these two distinctive life course prototypes, we propose a subtype distinction for research on the origins and lifetime course of major depression. A pressing goal is to determine at the time of depression's first onset who will follow which clinical trajectory. The lack of recognition of this distinction has resulted in many obstacles, including conceptual biases, methodological oversights, and definitional dead ends. Current theories are reviewed and compared. The implications for contemporary diagnostic controversies, reevaluating research on treatment and prevention, and enhancing the predictive strength of traditionally weak indicators of recurrences and recurrent depression are discussed.

Vascular Contributions to Brain Health: Cross-Cutting Themes.

As life expectancy grows, brain health is increasingly seen as central to what we mean by successful aging-and vascular brain health as central to overall brain health. Cerebrovascular pathologies are highly prevalent independent contributors to age-related cognitive impairment and at least partly modifiable with available treatments. The current Focused Update addresses vascular brain health from multiple angles, ranging from pathophysiologic mechanisms and neuroimaging features to epidemiologic risk factors, social determinants, and candidate treatments. Here we highlight some of the shared themes that cut across these distinct perspectives: (1) the lifetime course of vascular brain injury pathogenesis and progression; (2) the scientific and ethical imperative to extend vascular brain health research in non-White and non-affluent populations; (3) the need for improved tools to study the cerebral small vessels themselves; (4) the potential role for brain recovery mechanisms in determining vascular brain health and resilience; and (5) the cross-pathway mechanisms by which vascular and neurodegenerative processes may interact. The diverse perspectives featured in this Focused Update offer a sense of the multidisciplinary approaches and collaborations that will be required to launch our populations towards improved brain health and successful aging.

Possible role of the mitochondrial genome in the pathogenesis of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic renal disease in adults and is due to heterozygous germ line variants in either PKD1, PKD2 or rarely other genes. It is characterized by marked intra-familial disease variability suggesting that other genetic and/or environmental factors are involved in determining the lifetime course ADPKD. Recently, research indicates that polycystin-mediated mitochondrial dysfunction and metabolic re-programming contributes to the progression of ADPKD. Although biochemical abnormalities have gained the most interest, variants in the mitochondrial genome could be one of the mechanisms underlying the phenotypic variability in ADPKD. This narrative review aims to evaluate the role of the mitochondrial genome in the pathogenesis of APDKD.

Duration of Treatment in Electroconvulsive Therapy Among Patients Beginning With Acute Course Right Unilateral Brief Pulse Stimuli.

Right unilateral brief pulse (RUL-BP) electroconvulsive therapy (ECT) has been adopted as a technique for reducing the cognitive side effects of ECT relative to sine wave or bilateral treatments, but it is unknown how often patients are transitioned to alternative electrode placements. This study analyzes time in first lifetime acute course RUL-BP ECT. A single-center retrospective chart review was conducted of adult patients receiving a first lifetime course of ECT from 2000 to 2017 beginning with individualized seizure threshold determination using RUL-BP treatment parameters. A total of 1383 patients met study criteria and received a mean number of 9.4 ± 3.1 treatments, of which 7.6 ± 3.3 were using RUL-BP stimuli. Only 37.5% of patients were transitioned from RUL to bilateral treatments. Younger patients and those diagnosed with bipolar disorder were more likely to transition from RUL-BP to bilateral treatments, but the overall number of treatments did not differ based on age or primary diagnosis. Among patients who begin treatment with RUL-BP ECT, more than 60% use exclusively those parameters throughout their acute course.

Course of tic disorders over the lifespan.

To summarize and update information on the course of tic disorders from childhood through later life. Tics tend to improve substantially over the first year after they appear. However, contrary to widespread opinion, tics usually last longer than one year, though usually at minimal severity. Tics often wane to clinical insignificance over the teen years, possibly resurging occasionally over the lifespan. However, in an important minority of patients, tics remain clinically relevant throughout life. Tics rarely first come to clinical attention later in adulthood, but new reports describe additional such cases. Recent publications have shown tics to persist past a few months more often than previously thought, though often at minimal severity, and recurrence after an asymptomatic period is common. The safety and efficacy of behavior therapy for tics, together with prospective indicators of early prognosis, make feasible the possibility of bettering the lifetime course of tic disorders with early intervention.

Neutrophil-to-Lymphocyte Ratio as a Cardiovascular Risk Marker May Be Less Efficient in Women Than in Men.

Cardiovascular disease (CVD) is the leading cause of death in women, although traditionally, it has been considered as a male dominated disease. Chronic inflammation plays a crucial role in the development of insulin resistance, diabetes type 2 and CVD. Since studies on women were scarce, in order to improve diagnosis and treatment of CVD, there is a need to improve understanding of the role of inflammation in the development of CVD in women. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive and widely available marker of inflammation, and has been studied in cardio-metabolic disorders. There is a paucity of data on sex specific differences in the lifetime course of NLR. Men and women differ to each other in sex hormones and characteristics of immune reaction and the expression of CVD. These factors can determine NLR values and their variations along the life course. In particular, menopause in women is a period associated with profound physiological and hormonal changes, and is coincidental with aging. An emergence of CV risk factors with aging, and age-related changes in the immune system, are factors that are associated with an increase in prevalence of CVD in both sexes. The aim of this review is to comprehend the available evidence on this issue, and to discuss sex specific differences in the lifetime course of NLR in the light of immune and inflammation mechanisms.

Economic evaluation of betibeglogene autotemcel (Beti-cel) gene addition therapy in transfusion-dependent β-thalassemia

ABSTRACT Background Standard of care (SoC) for transfusion-dependent β-thalassemia (TDT) requires lifelong, regular blood transfusions as well as chelation to reduce iron accumulation. Objective This study investigates the cost-effectiveness of betibeglogene autotemcel (‘beti-cel’; LentiGlobin for β-thalassemia) one-time, gene addition therapy compared to lifelong SoC for TDT. Study design Microsimulation model simulated the lifetime course of TDT based on a causal sequence in which transfusion requirements determine tissue iron levels, which in turn determine risk of iron overload complications that increase mortality. Clinical trial data informed beti-cel clinical parameters; effects of SoC on iron levels came from real-world studies; iron overload complication rates and mortality were based on published literature. Setting USA; commercial payer perspective Participants TDT patients age 2–50 Interventions Beti-cel is compared to SoC. Main outcome measure Incremental cost-effectiveness ratio (ICER) utilizing quality-adjusted life-years (QALYs) Results The model predicts beti-cel adds 3.8 discounted life years (LYs) or 6.9 QALYs versus SoC. Discounted lifetime costs were $2.28 M for beti-cel ($572,107 if excluding beti-cel cost) and $2.04 M for SoC, with a resulting ICER of $34,833 per QALY gained. Conclusion Beti-cel is cost-effective for TDT patients compared to SoC. This is due to longer survival and cost offset of lifelong SoC.

Anxiety and Depression: A Key to Understanding the Complete Expression of Personality Disorders.

Anxiety and depressive disorders affect one fourth of the population. Personality disorders often present comorbid with anxiety and depressive disorders during the lifetime course of the illness. To fully explore the interplay between personality disorders and anxiety or depression, 179 patients, consecutively admitted to the Anxiety and Depression Outpatient Department, were clinically evaluated and tested with the Mini-International Neuropsychiatric Interview and the Iowa Personality Disorder Screening. Twenty-six percent of the total sample was affected only by personality disorders (PDs), and 21% had a comorbidity between a personality, anxiety, and/or depressive disorder (Comorbidity). Compared with PDs, Comorbidity used more antipsychotics and benzodiazepines (4.3% vs. 9.6%, χ2 = 0.267; 43.4 vs. 72.6, p = 0.004), showing a worse clinical picture, and expressed more personality traits even without statistical significance (6.863 ± 2.328 vs. 7.609 ± 1.674, p = 0.105). The different impact of personality disorders compared with anxiety and/or depression has to be further analyzed in terms of economic load and resource allocation.

Rate of continuing acute course treatment using right unilateral ultrabrief pulse electroconvulsive therapy at a large academic medical center.

Right unilateral ultrabrief pulse (RUL-UBP) ECT has emerged as a promising technique for minimizing cognitive side effects of ECT while retaining clinical efficacy, but it is unknown how often patients will require alternative treatment parameters and at what point in the treatment course this occurs. To better define this problem, this study analyzes continuation in RUL-UBP ECT in a retrospective cohort of patients beginning acute course treatment. A single-center retrospective chart review was conducted of adult patients receiving a first lifetime course of ECT from 2010 to 2017 starting with RUL-UBP treatment parameters. 1793 patients met study criteria. Patients received a mean of 10.0 ± 3.2 ECT treatments, of which a mean of 8.4 ± 3.4 were RUL-UBP treatments; proportion using RUL-UBP through 12 treatments was 57.8%. In total, 65.6% of patients were treated with RUL-UPB ECT exclusively. Mean dose increased from 7.6 × seizure threshold at the second RUL-UBP treatment to 14.3 × seizure threshold at the twelfth RUL-UBP treatment. Rates of continuation in RUL-UBP ECT did not differ based on age or on primary diagnosis of major depression vs. bipolar disorder. Among patients beginning acute-course treatment using RUL-UPB ECT, two thirds were treated with these parameters exclusively. Among patients who received twelve RUL-UBP treatments, mean final dose was 14.3 × seizure threshold. Further studies regarding optimal dosing of RUL-UBP ECT are indicated.

Ruminative Inertia and Its Association With Current Severity and Lifetime Course of Depression

Rumination has been consistently shown to play a critical role in the severity and course of depression. Relatively understudied, however, is the nature of rumination across time and how individual differences in the temporal dynamics of rumination may be related to depression. In this study, we investigated the association between ruminative inertia (the degree to which rumination levels are resistant to change from day to day) and both current and past depression in a clinical sample. Participants ( N = 71) completed daily-diary surveys for 3 weeks. Ruminative inertia was positively associated with current depressive symptoms and negatively associated with the number of past depressive episodes. These findings suggest that more severe depressive symptoms are associated with rumination that is more resistant to change over time, whereas a greater number of past depressive episodes is related to less ruminative inertia. Additional research is needed to explore the directionality of these effects.

Total Charge Required to Induce a Seizure in a Retrospective Cohort of Patients Undergoing Dose Titration of Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy.

The use of ultrabrief pulse (UBP) stimuli and individual seizure threshold determination have been proposed as ways of minimizing the cognitive side effects of electroconvulsive therapy (ECT), but large samples of patients receiving UBP ECT are lacking. This study reports a retrospective cohort of patients receiving an index course of right unilateral UBP ECT and characterizes the amount of charge required to induce a seizure. A single-center retrospective chart review was conducted of adult patients receiving a first lifetime course of ECT using an UBP titration from 2005 to 2017. There were 2328 patients that received a dose titration during the study period, with a mean dose of 21.82 ± 21.61 mC applied to induce a seizure. During the early part of the study period, a mean dose of 18.73 ± 8.99 mC was used, with 28% of patients seizing at a dose of less than 19.2 mC. In the later period, the initial step of dose titration was standardized at 19.2 mC, yielding a mean initial dose to induce a seizure of 22.72 ± 24.00 mC. Mean seizure thresholds may be lower than reported in previous studies, and a significant proportion of patients may have a seizure threshold lower than the first step of many existing dose titration protocols.

Persistent depressive disorder across the adult lifespan: results from clinical and population-based surveys in Germany

BackgroundAlthough the individual and economic disease burden of depression is particularly high for long-term symptoms, little is known of the lifetime course of chronic depression. Most evidence derives from clinical samples, and the diagnostic distinction between persistent depressive disorder (PDD) and non-chronic major depression (NCMDD) is still debated. Thus, we examined characteristics of PDD among clinical vs. non-clinical cases, and the associated disease burden at a population level.MethodsData were drawn from the mental health module of the German Health Interview and Examination Survey for Adults (DEGS1-MH, 2009–2012, n = 4483) and a clinical sample of PDD inpatients at Charité – Universitätsmedizin Berlin (2018–2019, n = 45). The DSM-5 definition of PDD was operationalized a priori to the study using interview-based DSM-IV diagnoses of dysthymia and major depression lasting at least 2 years in both surveys. Additional depression characteristics (depression onset, self-classified course, suicidality, comorbid mental disorders, treatment history and current depressive symptoms [Patient Health Questionnaire-9]) were assessed. In the DEGS1-MH, health-related quality of life (Short Form Health Survey-36, SF-36), chronic somatic conditions, number of sick days (past 12 months) or days with limitations in normal daily life activities (past 4 weeks), and health service utilization (past 12 months) were compared for PDD vs. NCMDD.ResultsPDD cases from the clinical sample had a significantly earlier depression onset, a higher proportion of self-classification as persistent course, and treatment resistance than PDD and NCMDD cases in DEGS1-MH. At a population level, PDD cases showed worse outcomes compared with NCMDD cases in terms of somatic comorbidity, SF-36 mental component score, and activity limitations owing to mental health problems, as well as a higher risk for outpatient mental health care contact.ConclusionsThe distinction between PDD and NCMDD proposed for DSM-5 seems warranted. Early onset depression, self-classification as persistent depressive course, and treatment resistance are suggested as markers of more severe and chronic depression courses. At a population level, PDD is associated with remarkably higher individual and economic disease burden than NCMDD, highlighting the need to improve medical recognition of chronic courses and establish specific treatment concepts for chronic depression.

Life stress and major depression: The mysteries of recurrences.

Approximately half of the people who suffer a major depressive episode for the first time experience recurrences, while the other half do not. Among the initially depressed, however, who will have recurrences remains a mystery, and cannot be forecasted with any statistical or clinical confidence. It is well documented, though, that highly stressful life events commonly precede first episodes of major depression, and that these experiences become progressively less common prior to recurrences. Determining the basis for this consistent empirical observation holds promise for discovering among the initially depressed who will become recurrent, helping to solve the current-day conundrum of recurrences. The present article has 2 overarching objectives. First, we evaluate stress sensitization, the prevailing theory for explaining the decreasing association of major life events with successive recurrences. Conceptual gaps, discrepancies, and misunderstandings are found for understanding the decreasing association, as well as for understanding recurrences. Research practices and logical errors also are exposed that compromise the integrity of the existing empirical record. Second, alternative theoretical accounts are proposed to explain the decreasing association of major life stress with recurrences. Two "dual pathway models" provide viable alternative explanations, fill in existing theoretical gaps, and supply additional advantages for understanding life stress, depression, and recurrences. Recommendations are made for evaluating the 3 respective models. In closing, limitations and remaining questions are discussed for discovering who, early in the lifetime course of major depression, is likely to have a lifetime of repeated recurrences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Novel treatment approaches and future perspectives in follicular lymphoma.

Follicular lymphoma (FL) is a common B-cell malignancy characterized by relatively indolent growth and incurability with an expected lifetime course of serial intermittent treatment courses. Many patients with FL have lives shortened by the disease and despite a relatively favorable prognosis relative to other incurable systemic malignancies, optimal management of FL has not been achieved. This review focuses on identifying both patients for whom novel therapies might be most beneficial as well as systematically reviewing novel strategies at various levels of investigation. Prognostic markers incorporating clinical measurements and tumor genetics are discussed, yet at the time of diagnosis do not yet powerfully discriminate patients for whom specific strategies are beneficial. Reassessment of prognosis after evaluating the response to initial therapy is the most powerful identifier of those in need of novel management strategies. For initial therapy of high burden systemic disease, anti-CD20 antibody along with chemotherapy or immunomodulators all offer relatively similar effects on overall survival with subtly different effects on progression-free survival and quality of life. Several new agents currently under investigation in the upfront setting are discussed. Perhaps the best testing ground for novel therapies is in patients with early relapse following initial immunochemotherapy. Ongoing research in multiple therapy classes including, novel monoclonal antibodies, antibody drug conjugates, immunomodulatory agents, intracellular pathway inhibitors, immune checkpoint inhibitors, and epigenetic regulators are discussed herein.