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Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change.
Methods
This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories.
Results
The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed.
Conclusions
FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions.
Climate change is resulting in global changes to sea level and wave climates, which in many locations significantly increase the probability of erosion, flooding and damage to coastal infrastructure and ecosystems. Therefore, there is a pressing societal need to be able to forecast the morphological evolution of our coastlines over a broad range of timescales, spanning days-to-decades, facilitating more focused, appropriate and cost-effective management interventions and data-informed planning to support the development of coastal environments. A wide range of modelling approaches have been used with varying degrees of success to assess both the detailed morphological evolution and/or simplified indicators of coastal erosion/accretion. This paper presents an overview of these modelling approaches, covering the full range of the complexity spectrum and summarising the advantages and disadvantages of each method. A focus is given to reduced-complexity modelling approaches, including models based on equilibrium concepts, which have emerged as a particularly promising methodology for the prediction of coastal change over multi-decadal timescales. The advantages of stable, computationally-efficient, reduced-complexity models must be balanced against the requirement for good generality and skill in diverse and complex coastal settings. Significant obstacles are also identified, limiting the generic application of models at regional and global scales. Challenges include the accurate long-term prediction of model forcing time-series in a changing climate, and accounting for processes that can largely be ignored in the shorter term but increase in importance in the long term. Further complications include coastal complexities, such as the accurate assessment of the impacts of headland bypassing. Additional complexities include complex structures and geology, mixed grain size, limited sediment supply, sources and sinks. It is concluded that with present computational resources, data availability limitations and process knowledge gaps, reduced-complexity modelling approaches currently offer the most promising solution to modelling shoreline evolution on daily-to-decadal timescales.
Species tend to peak in abundance at different times after fires. Over time, species richness (α) and landscape heterogeneity are prone to increase and lead to greater between-site diversity (β). However, post-fire salvage logging can reduce β-diversity, both directly and through its influence on succession. The as-yet understudied response of land snails to long-term habitat modification after wildfires and forest management is important for decision-making in forest restoration and conservation. We expected to detect differences in land snails and diversity in both the short and long term and between treatments in a natural park in the Mediterranean Basin. However, our results showed that post-fire management was a non-significant variable for snail community diversity, the exception being open-habitat endemic species. Plant succession and leaf litter cover were the main variables that shaped snail diversity and abundance over time after fires. Eighteen years after a fire, the land snail diversity had improved and the community composition had diversified, irrespective of the post-fire treatment, but threatened species disappeared and the total snail numbers had notably declined. To preserve threatened open-habitat species, prescribed fires and livestock grazing are recommended in combination with mature areas that can act as shelters where forest snails can recover from future disturbances.
First-episode psychosis is a critical period for early interventions to reduce the risk of poor outcomes and relapse as much as possible. There are now many studies revealing the patterns of course in the short and medium terms, but uncertainties about the long-term outcomes of symptomatology remain to be ascertained.
Objectives
First, we ascertained whether the structure of psychopathological symptoms, dimensions and domains of psychopathology remains invariant over time between first-episode psychosis and long-term follow-up. Second, we analysed the changes in the interrelationships of psychopathological symptoms, dimensions and domains of psychopathology between FEP and long-term follow-up at three levels.
Methods
We performed network analysis to investigate first-episode and long-term stages of psychosis at three levels of analysis: micro, meso and macro. The sample was a cohort of 510 patients with first-episode psychoses from the SEGPEP study, who were reassessed at the long-term follow-up (n = 243). We used the Comprehensive Assessment of Symptoms and History (CASH) for their assessments.
Results
Our results showed a similar pattern of clustering between first episodes and long-term follow-up in seven psychopathological dimensions at the micro level, 3 and 4 dimensions at the meso level, and one at the macro level. They also revealed significant differences between first-episode and long-term network structure and centrality measures at the three levels.
Conclusions
Our findings suggest that disorganization symptoms have more influence in long-term stabilized patients. The main results of the current study add evidence to the hierarchical, dimensional and longitudinal structuring of first-episode psychoses.
Edited by
James Law, University of Newcastle upon Tyne,Sheena Reilly, Griffith University, Queensland,Cristina McKean, University of Newcastle upon Tyne
Language is fundamental to success in many life domains, and children showing vulnerabilities in their language development may be at risk of poorer lifelong outcomes. This chapter synthesises evidence from longitudinal population-based and community samples to describe the long-term psychosocial outcomes associated with a history of language problems. Notably, this chapter centres on the outcomes of late talkers and children with developmental language disorder (DLD). The chapter begins by profiling the outcomes experienced when language difficulties are identified at a single point in the child’s development. Next, the influence of changes in language profiles over time on the long-term psychosocial outcomes is considered. Throughout the chapter, outcomes are explored across key areas including literacy and numeracy, educational and vocational attainment, emotional and behavioural functioning, social connections, and mental health and well-being. The studies presented show that while heterogeneity exists, children with language problems at one point in development are at increased risk of difficulties in other domains of life, and these adverse outcomes can persist into adulthood.
Neuropsychological impairment represents a key aspect of bipolar disorder (BD) that is evident even in early-course patients and is a strong predictor of functional outcomes among those affected. Previous meta-analyses of longitudinal studies suggest that BD-related cognitive deficits may not progress along the course of the disorder. However, short test-retest periods were used in most primary studies and comparisons with healthy controls were limited. The aim of this review was to synthesize the findings of research reports comparing long-term neurocognitive trajectories between BD patients and healthy individuals. PubMed, PsycINFO, and Scopus databases were searched from inception through July 2021. Publications were considered for inclusion if they reported cognitive test scores of BD patients and healthy controls at two different time points, with a minimum test-retest interval of 5 years. Fifteen studies compared the long-term course of cognition in BD patients with that of healthy controls. Ten of these were included in the quantitative analysis and involved 540 BD patients and 644 healthy individuals (mean follow-up period: 8.9 years). Patient-control effect sizes (standardized mean differences) were calculated for test-score changes in 24 neuropsychological variables and combined by means of meta-analytic procedures. No significant differences were found between patients and controls regarding long-term cognitive outcomes. These findings are consistent with previous shorter-term longitudinal meta-analyses and do not provide evidence for progressive cognitive deterioration in most bipolar individuals. Future studies should address the longitudinal course of cognition in different subgroups of BD patients and its prognostic and therapeutic value.
Commercialization of 2,4-D-resistant soybean varieties allows for postemergence (POST) applications of 2,4-D in soybean. With the increase in POST applications of 2,4-D in soybean, shifts in weed populations may occur. A long-term field trial was conducted over 7 yr in a corn-soybean rotation. Weed populations were subjected to four herbicide strategies with variable levels of 2,4-D reliance. The strategies used included 1) diversified glyphosate strategy with six herbicide sites of action (SOAs); 2) 2,4-D reliant strategy with three SOAs; 3) diversified 2,4-D reliant strategy with seven SOAs; and 4) fully diversified strategy with eight SOAs. Soil residual herbicides were used for both corn and soybean years, except for the 2,4-D-reliant strategy, which used only a residual herbicide during the corn years. A 52% or greater reduction in weed densities for all herbicide strategies, except the 2,4-D-reliant strategy, was observed by the end of the study. However, the density of weeds tolerant to 2,4-D, such as monocots, increased after 3 yr of selection pressure, and more than doubled after 5 yr of selection pressure in the 2,4-D-reliant strategy. Additionally, in the 2,4-D-reliant strategy with three SOAs, species richness was 30% higher in the soil seedbank compared to herbicides strategies with six or more SOAs. In order to delay weed shifts, diversified herbicide strategies with more than three SOAs that include residual herbicides should be used in corn:soybean rotational systems that use 2,4-D-resistant soybean.
Bloodstream fungal infections have a high mortality rate. There is little data about the long-term mortality rate of fungaemia.This study aimed to explore the mortality of fungaemia and the influencing factors associated with death. In total, 204 intensive care unit (ICU) patients with fungaemia from Multi-parameter Intelligent Monitoring in Intensive Care-III (MIMIC-III) Database were studied. Age, gender, major underlying diseases, data about vital signs and blood test results were analysed to identify the predictors of the mortality and prognosis of fungaemia in ICU patients. Cox regression models were constructed, together with Kaplan−Meier survival curves. The 30-day, 1-year, 2-year, 3-year and 4-year mortality rates were 41.2%, 62.3%, 68.1%, 72.5% and 75%, respectively. Age (P < 0.001, OR = 1.530; P < 0.001, OR = 1.485),serum bilirubin (P = 0.016, OR = 2.125;P = 0.001, OR = 1.748) and international normalised ratio (INR) (P = 0.001, OR = 2.642; P < 0.001 OR = 2.065) were predictors of both the 30-day and 4-year mortality rates. Renal failure (P = 0.009, OR = 1.643) performed good in prediction of the 4-year mortality. The mortality of fungaemia is high. Age,the serum bilirubin and INR are good predictors of the 30-day and 4-year mortality rates of fungaemia. Renal failure has good performance in predicting the long-term mortality.
Several types of psychological treatment for posttraumatic stress disorder (PTSD) are considered well established and effective, but evidence of their long-term efficacy is limited. This systematic review and meta-analysis aimed to investigate the long-term outcomes across psychological treatments for PTSD. MEDLINE, Cochrane Library, PTSDpubs, PsycINFO, PSYNDEX, and related articles were searched for randomized controlled trials with at least 12 months of follow-up. Twenty-two studies (N = 2638) met inclusion criteria, and 43 comparisons of cognitive behavioral therapy (CBT) were available at follow-up. Active treatments for PTSD yielded large effect sizes from pretest to follow-up and a small controlled effect size compared with non-directive control groups at follow-up. Trauma-focused treatment (TFT) and non-TFT showed large improvements from pretest to follow-up, and effect sizes did not significantly differ from each other. Active treatments for comorbid depressive symptoms revealed small to medium effect sizes at follow-up, and improved PTSD and depressive symptoms remained stable from treatment end to follow-up. Military personnel, low proportion of female patients, and self-rated PTSD measures were associated with decreased effect sizes for PTSD at follow-up. The findings suggest that CBT for PTSD is efficacious in the long term. Future studies are needed to determine the lasting efficacy of other psychological treatments and to confirm benefits beyond 12-month follow-up.
Antipsychotic medications are used in a wide range of mental health and neurodevelopmental conditions in children and adolescents. Their efficacy and tolerability with long-term use have not been clearly established. We aimed to conduct a systematic review and meta-analysis to evaluate the long-term use of antipsychotics in children and adolescents. All relevant double-blind randomized control trials (RCTs), on any antipsychotic used for 12 weeks or longer in any mental health/neurodevelopmental condition in this age group, were included. We evaluated several efficacy and tolerability measures. Meta-analysis was performed for adverse events. Seven RCTs were identified (n = 939, age = 5-17 years), four on aripiprazole and three on risperidone. All studies reported symptomatic/functional improvements or more time before discontinuation with antipsychotics compared to placebo. Weight gain was identified as a significant side effect with antipsychotics. Serum prolactin was reduced with aripiprazole and increased with risperidone, and abdominal pain/discomfort, respiratory tract infections, were more common with Aripiprazole compared to placebo. Musculoskeletal pain may be more common with aripiprazole compared to placebo. Use of antipsychotics for 12 weeks or longer may be associated with symptomatic/functional improvements, but may be associated with additional side effects compared to short-term treatment. Further research in this population is needed.
This chapter explores the rationale for a pension fund to integrate sustainability in its investment analysis and decisions, and why engagement is an important tool for an active and long-term investor in creating value for beneficiaries. Based on our experiences this does not neccessarily carry the higher costs traditionally associated with active management, but it will put higher demands on asset managers and analysts to understand and translate new data and information into the fundamental financial analysis. In a time where increasing capital is being allocated to passive index strategies, we argue that active and long-term owners foster corporate accountability and a broader concept of value creation. We stress the importance of developing in-house capacity for engagement and stewardship, as this enables leverage on key industry insights, while at the same time recognising when investor collaboration towards a common objective is more efficent.
Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia.
Methods
Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score.
Results
About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104.
Conclusion
In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.
The addition of dicamba as a weed control option in soybean [Glycine max (L.) Merr.] is a valuable tool. However, this technology must be utilized with other herbicide sites of action (SOAs) to reduce selection pressure on weed communities and ensure its prolonged usefulness. A long-term trial was conducted for 7 yr in Indiana to evaluate weed community densities and species richness with four levels of dicamba selection pressure in a corn (Zea mays L.)–soybean rotation. Monocot densities and richness increased over time in the dicamba-reliant treatment. Dicot densities in the dicamba-reliant treatment declined over time, but dicot richness increased. The soil weed seedbank was affected by the varying herbicide strategies. The dicamba-reliant strategy had greater than 43% higher total weed density than all other treatments, primarily due to having a monocot density that was at least 71% higher than the other treatments. The fully diversified strategy with eight SOAs and residual herbicides used every year had the lowest total weed species richness in the soil seedbank, which supported the in-field observations.
It has long been known that most patients with bipolar disorder have a course marked by multiple recurrence of major depressive and manic episodes. More recently, many epidemiological studies have shown that at least 50% of unipolar depressive patients have one or more subsequent episodes of depression in their lifetimes. Likewise, relapse following successful short-term treatment of depression is so common that it is now recommended to prolong treatment in the form of maintenance pharmacotherapy. Interest in preventing the recurrence of depression has been stimulated by the results from long-term trials involving antidepressant drugs and lithium. However, these pharmacological studies suffer somewhat from methodological deficits, making difficult any clear and complete interpretation of their results. While some methodological recommendations have now been established to compensate for previous deficits (eg, definition of relapse and recurrence, duration of acute and maintenance treatments, statistical analysis of efficacy), unfortunately, many key points still remain to be resolved (eg, selection of patients, dosage in maintenance and prophylactic phases, maximum length of a course of treatment, etc).
Long-term treatment with antidepressants is now an accepted strategy in the management of depression. The demonstration of efficacy in this setting requires specific placebo-controlled trials of patients with recurrent depression studied after an adequate period of euthymia and for a long period of follow-up. This review examines the evidence for the prophylactic efficacy of antidepressant therapy with particular emphasis on the selective serotonin reuptake inhibitor, paroxetine.
Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes.
Methods
The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers.
Results
During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319 mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score.
Conclusions
In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.
The long-term effects of pediatric concussion on white matter microstructure are poorly understood. This study investigated long-term changes in white matter diffusion properties of the corpus callosum in youth several years after concussion.
Methods:
Participants were 8–19 years old with a history of concussion (n = 36) or orthopedic injury (OI) (n = 21). Mean time since injury for the sample was 2.6 years (SD = 1.6). Participants underwent diffusion magnetic resonance imaging, completed cognitive testing, and rated their post-concussion symptoms. Measures of diffusivity (fractional anisotropy, mean, axial, and radial diffusivity) were extracted from white matter tracts in the genu, body, and splenium regions of the corpus callosum. The genu and splenium tracts were further subdivided into 21 equally spaced regions along the tract and diffusion values were extracted from each of these smaller regions.
Results:
White matter tracts in the genu, body, and splenium did not differ in diffusivity properties between youth with a history of concussion and those with a history of OI. No significant group differences were found in subdivisions of the genu and splenium after correcting for multiple comparisons. Diffusion metrics did not significantly correlate with symptom reports or cognitive performance.
Conclusions:
These findings suggest that at approximately 2.5 years post-injury, youth with prior concussion do not have differences in their corpus callosum microstructure compared to youth with OI. Although these results are promising from the perspective of long-term recovery, further research utilizing longitudinal study designs is needed to confirm the long-term effects of pediatric concussion on white matter microstructure.
The world’s most fragile states contain 38% of the world’s population and are among the world’s poorest. In these states up to 10% of all deaths and 20% of deaths among young adults may be attributed to untreated surgical disease, and over 500 000 women die each year during childbirth. International aid organizations have a presence in fragile states notably the International Committee of the Red Cross (ICRC). The potential for long-term field missions to address disparities in access to acute trauma, surgical, and obstetric care is not to be underestimated. Every opportunity for training and support of local health care staff is to be valued. The success of long-term deployments rests on sound planning before the implementation of programs and honest appraisal of ongoing programs.
Highly weathered soils from humid tropics naturally have low contents of available potassium (K) to plants. Under these conditions, the K deprivation can change the equilibrium among cations in the soil and the nutritional status of some crops as soybean (Glycine max (L.) Merrill). A field experiment related to K fertilisation, spring soybean and diverse species of fall/winter crops, such as wheat (Triticum aestivum L.), corn (Zea mays L.), sunflower (Helianthus annuus L.) or oat (Avena strigosa L.), has been carried out in Southern Brazil since 1983. The K deprivation for 8 years reduced soybean grain yield and the K contents in soil and plant tissues. K extractants, such as Mehlich-1 and ion exchange resins, had diverse sensitivities with the variation in the K exchangeable contents induced by K rates. The increased soil K content after K fertilisation reduced calcium (Ca) and magnesium (Mg) contents in index leaves and altered its contents in the soil extracted by 1 mol L−1 KCl and ion exchange resins. Among the micronutrients, only B contents changed due to increased K rates, and had significant correlations with K and Ca contents in index leaves. The calculated Diagnosis and Recommendation Integrated System (DRIS) indices were compatible with soybean yield and K contents in soybean index leaves.
John H. Esling, University of Victoria, British Columbia,Scott R. Moisik, Nanyang Technological University, Singapore,Allison Benner, University of Victoria, British Columbia,Lise Crevier-Buchman, Centre National de la Recherche Scientifique (CNRS), Paris
Terminology for voice quality is revised, particularly for the lower vocal tract. The concepts of ‘voice quality’ as the long-term, habitual postural settings in an accent and ‘voice quality’ as the vibratory, phonatory portion of speech are reconciled through the laryngeal articulator mechanism that explains how multiple configurational adjustments and vibratory elements are achieved in the lower vocal tract. The origins of voice quality theory are reviewed, and articulatory settings of the laryngeal mechanism, velopharyngeal opening, the tongue, the jaw, and the lips are reviewed. The descriptions from Laver (1980) are reinforced, connections to laryngeal articulation are made explicit, and the musculature responsible for each setting is outlined. New drawings of the mechanisms of the vocal tract provide a fresh perspective on articulatory movements and resulting auditory qualities. Pharyngeal/epiglottal articulations are remapped, and their status as laryngeal configurations is made explicit.