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There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method.
Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects.
Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining.
An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.
Solutions like crowd screening and machine learning can assist systematic reviewers with heavy screening burdens but require training sets containing a mix of eligible and ineligible studies. This study explores using PubMed's Best Match algorithm to create small training sets containing at least five relevant studies.
Six systematic reviews were examined retrospectively. MEDLINE searches were converted and run in PubMed. The ranking of included studies was studied under both Best Match and Most Recent sort conditions.
Retrieval sizes for the systematic reviews ranged from 151 to 5,406 records and the numbers of relevant records ranged from 8 to 763. The median ranking of relevant records was higher in Best Match for all six reviews, when compared with Most Recent sort. Best Match placed a total of thirty relevant records in the first fifty, at least one for each systematic review. Most Recent sorting placed only ten relevant records in the first fifty. Best Match sorting outperformed Most Recent in all cases and placed five or more relevant records in the first fifty in three of six cases.
Using a predetermined set size such as fifty may not provide enough true positives for an effective systematic review training set. However, screening PubMed records ranked by Best Match and continuing until the desired number of true positives are identified is efficient and effective.
The Best Match sort in PubMed improves the ranking and increases the proportion of relevant records in the first fifty records relative to sorting by recency.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Major depressive disorder (MDD) is a leading cause of morbidity and mortality. Shortfalls in treatment quantity and quality are well-established, but the specific gaps in pharmacotherapy and psychotherapy are poorly understood. This paper analyzes the gap in treatment coverage for MDD and identifies critical bottlenecks.
Seventeen surveys were conducted across 15 countries by the World Health Organization-World Mental Health Surveys Initiative. Of 35 012 respondents, 3341 met DSM-IV criteria for 12-month MDD. The following components of effective treatment coverage were analyzed: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) adequate severity-specific combination of both.
MDD prevalence was 4.8% (s.e., 0.2). A total of 41.8% (s.e., 1.1) received any mental health services, 23.2% (s.e., 1.5) of which was deemed effective. This 90% gap in effective treatment is due to lack of utilization (58%) and inadequate quality or adherence (32%). Critical bottlenecks are underutilization of psychotherapy (26 percentage-points reduction in coverage), underutilization of psychopharmacology (13-point reduction), inadequate physician monitoring (13-point reduction), and inadequate drug-type (10-point reduction). High-income countries double low-income countries in any mental health service utilization, adequate pharmacotherapy, adequate psychotherapy, and adequate combination of both. Severe cases are more likely than mild-moderate cases to receive either adequate pharmacotherapy or psychotherapy, but less likely to receive an adequate combination.
Decision-makers need to increase the utilization and quality of pharmacotherapy and psychotherapy. Innovations such as telehealth for training and supervision plus non-specialist or community resources to deliver pharmacotherapy and psychotherapy could address these bottlenecks.
Intimations of death often cause symptoms or syndromes of mental or emotional disorder, of which anxiety and depression are the most common. It is entirely appropriate, therefore, for mental health services to be involved with those who care for the dying in whatever setting. Old age psychiatrists have recognized their more direct role in caring for dying patients for many years., And some years ago a particular impetus emerged behind the notion of palliative care in dementia., This followed the early research by Ladislav Volicer and his colleagues in the dementia special care unit (DSCU) as part of the Geriatrics Research Education and Clinical Center at the E.N. Rogers Memorial Veterans Hospital in Bedford, Massachusetts. Since then there has been a burgeoning both in the field and in the literature. Gradually, different sorts of ways to provide palliative care for people with dementia have also emerged.
To develop a staff training intervention for agitation in people with severe dementia, reaching end-of-life, residing in nursing homes (NHs), test feasibility, acceptability, and whether a trial is warranted.
Feasibility study with pre- and post-intervention data collection, qualitative interviews, and focus groups.
Three NHs in South East England with dementia units, diverse in terms of size, ownership status, and location.
Residents with a dementia diagnosis or scoring ≥2 on the Noticeable Problems Checklist, rated as “severe” on Clinical Dementia Rating Scale, family carers, and staff (healthcare assistants and nurses).
Manualized training, delivered by nonclinical psychology graduates focusing on agitation in severe dementia, underpinned by a palliative care framework.
Main outcomes were feasibility of recruitment, data collection, follow-up, and intervention acceptability. We collected resident, family carer, and staff demographics. Staff provided data on resident’s agitation, pain, quality of life, and service receipt. Staff reported their sense of competence in dementia care. Family carers reported on satisfaction with end-of-life care. In qualitative interviews, we explored staff and family carers’ views on the intervention.
The target three NHs participated: 28 (49%) residents, 53 (74%) staff, and 11 (85%) family carers who were eligible to participate consented. Eight-four percent of staff attended ≥3 sessions, and we achieved 93% follow-up. We were able to complete quantitative interviews. Staff and family carers reported the intervention and delivery were acceptable and helpful.
The intervention was feasible and acceptable indicating a larger trial for effectiveness may be warranted.
To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes.
Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQHarvard) and Phenol-Explorer (SFFQPE) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDRPE). Validity was assessed using Spearman’s rank correlation coefficients deattenuated for random measurement error (rs), and reproducibility was assessed using rank intraclass correlation coefficients.
This validation study included primarily participants from two large observational cohort studies.
Six hundred forty-one men and 724 women.
When compared with two 7DDRPE, the validity of total flavonoid intake assessed by SFFQPE was high for both men and women (rs = 0·77 and rs = 0·74, respectively). The rs for flavonoid subclasses ranged from 0·47 for flavones to 0·78 for anthocyanins in men and from 0·46 for flavonols to 0·77 for anthocyanins in women. We observed similarly moderate (0·4–0·7) to high (≥0·7) validity when using SFFQHarvard estimates, except for flavonesHarvard (rs = 0·25 for men and rs = 0·19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0·69 (flavonolsPE) to 0·80 (proanthocyanidinsPE) in men and from 0·67 (flavonolsPE) to 0·77 (flavan-3-ol monomersHarvard) in women.
SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.
There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.
Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.
Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.
Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.
Family caregivers of people with dementia can experience loss and grief before death. We hypothesized that modifiable factors indicating preparation for end of life are associated with lower pre-death grief in caregivers.
Caregivers of people with dementia living at home or in a care home.
In total, 150 caregivers, 77% female, mean age 63.0 (SD = 12.1). Participants cared for people with mild (25%), moderate (43%), or severe dementia (32%).
Primary outcome: Marwit-Meuser Caregiver Grief Inventory Short Form (MMCGI-SF). We included five factors reflecting preparation for end of life: (1) knowledge of dementia, (2) social support, (3) feeling supported by healthcare providers, (4) formalized end of life documents, and (5) end-of-life discussions with the person with dementia. We used multiple regression to assess associations between pre-death grief and preparation for end of life while controlling for confounders. We repeated this analysis with MMCGI-SF subscales (“personal sacrifice burden”; “heartfelt sadness”; “worry and felt isolation”).
Only one hypothesized factor (reduced social support) was strongly associated with higher grief intensity along with the confounders of female gender, spouse, or adult child relationship type and reduced relationship closeness. In exploratory analyses of MMCGI-SF subscales, one additional hypothesized factor was statistically significant; higher dementia knowledge was associated with lower “heartfelt sadness.”
We found limited support for our hypothesis. Future research may benefit from exploring strategies for enhancing caregivers’ social support and networks as well as the effectiveness of educational interventions about the progression of dementia (ClinicalTrials.gov ID: NCT03332979).
There is increasing interest in the clinical and aetiological overlap between autism spectrum disorders and schizophrenia spectrum disorders, reported to co-occur at both diagnostic and trait levels. Individually, sub-clinical autistic and psychotic traits are associated with poor clinical outcomes, including increased depressive symptomatology, self-harming behaviour and suicidality. However, the implications when both traits co-occur remain poorly understood. The study aimed to (1) examine the relationship between autistic and psychotic traits and (2) determine if their co-occurrence increases depressive symptomatology, self-harm and suicidality.
Cross-sectional data from a self-selecting (online and poster advertising) sample of the adult UK population (n = 653) were collected using an online survey. Validated self-report measures were used to assess sub-clinical autistic and psychotic traits, depressive symptomatology, self-harming behaviour and suicidality. Correlation and regression analyses were performed.
A positive correlation between sub-clinical autistic and positive psychotic traits was confirmed (rs = 0.509, p < 0.001). Overall, autistic traits and psychotic traits were, independently, significant predictors of depression, self-harm and suicidality. Intriguingly, however, depression was associated with a negative interaction between the autistic domain attention to detail and psychotic traits.
This study supports previous findings that sub-clinical autistic and psychotic traits are largely independently associated with depression, self-harm and suicidality, and is novel in finding that their combined presence has no additional effect on depression, self-harm or suicidality. These findings highlight the importance of considering both autistic and psychotic traits and their symptom domains in research and when developing population-based depression prevention and intervention strategies.
Nearly half of care home residents with advanced dementia have clinically significant agitation. Little is known about costs associated with these symptoms toward the end of life. We calculated monetary costs associated with agitation from UK National Health Service, personal social services, and societal perspectives.
Prospective cohort study.
Thirteen nursing homes in London and the southeast of England.
Seventy-nine people with advanced dementia (Functional Assessment Staging Tool grade 6e and above) residing in nursing homes, and thirty-five of their informal carers.
Data collected at study entry and monthly for up to 9 months, extrapolated for expression per annum. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Health and social care costs of residing in care homes, and costs of contacts with health and social care services were calculated from national unit costs; for a societal perspective, costs of providing informal care were estimated using the resource utilization in dementia (RUD)-Lite scale.
After adjustment, health and social care costs, and costs of providing informal care varied significantly by level of agitation as death approached, from £23,000 over a 1-year period with no agitation symptoms (CMAI agitation score 0–10) to £45,000 at the most severe level (CMAI agitation score >100). On average, agitation accounted for 30% of health and social care costs. Informal care costs were substantial, constituting 29% of total costs.
With the increasing prevalence of dementia, costs of care will impact on healthcare and social services systems, as well as informal carers. Agitation is a key driver of these costs in people with advanced dementia presenting complex challenges for symptom management, service planners, and providers.
Integrating geophysical survey with the study of community settlement patterns can be challenging because of cultural and environmental factors including (1) site formation and house preservation, (2) the coordination of domestic tasks at extra-household scales, and (3) the survey environment of the study area. In this article, we present the results of a program of geophysical survey comprising magnetic susceptibility and magnetometry at Weeden Island (8Pi1)—a shell-bearing, wooded site with nearly pure sand soils on the Gulf Coast of Florida. Combining remote sensing techniques mitigated some of the challenges of surveying forested terrain while providing insight into community organization at a site with minimal preserved structural remains. Compared with previous traditional surveys of the area, the geophysical survey extended the recognized boundaries of occupational activity, provided additional definition to the spatial structure of deposits, and allowed us to identify specific domestic features. Excavations at each area of intensive occupation provided evidence about the organization of the domestic economy at the site and showed the potential of this approach to reveal significant patterns of community settlement.
To provide cross-national data for selected countries of the Americas on service utilization for psychiatric and substance use disorders, the distribution of these services among treatment sectors, treatment adequacy and factors associated with mental health treatment and adequacy of treatment.
Data come from data collected from 6710 adults with 12 month mental disorder surveys across seven surveys in six countries in North (USA), Central (Mexico) and South (Argentina, Brazil, Colombia, Peru) America who were interviewed 2001–2015 as part of the World Health Organization (WHO) World Mental Health (WMH) Surveys. DSM-IV diagnoses were made with the WHO Composite International Diagnostic Interview (CIDI). Interviews also assessed service utilization by the treatment sector, adequacy of treatment received and socio-demographic correlates of treatment.
Little over one in four of respondents with any 12 month DSM-IV/CIDI disorder received any treatment. Although the vast majority (87.1%) of this treatment was minimally adequate, only 35.3% of cases received treatment that met acceptable quality guidelines. Indicators of social-advantage (high education and income) were associated with higher rates of service use and adequacy, but a number of other correlates varied across survey sites.
These results shed light on an enormous public health problem involving under-treatment of common mental disorders, although the problem is most extreme among people with social disadvantage. Promoting services that are more accessible, especially for those with few resources, is urgently needed.
Fiona Sampson looks beyond any simplistic account of legacy in her nuanced tracing of Plath’s continuing influence on British poetry. While Plath left no substantial or explicit articulation of her poetics, her early published work indicates some of her own literary debts. The free verse which eventually muscles its way out of that initial formality is closely related, in both rhythm and register, to exactly contemporary work by Ted Hughes. Almost universally read by contemporary British poets, she contributes a Plathian dimension to contemporary British poetics as a whole. This is less apparent in today’s Confessional free verse, which owes much to life writing and oral forms, than in the continuation, alongside the Hardy/Larkin mainstream, of a more risk-taking, symbolic and higher-register tradition. Its protagonists include Sharon Olds, Louise Glück, Selima Hill and Denise Riley.