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Unlike a physical grand piano, a physical synthesis instrument, such as one of Pianoteq’s series of grand pianos, is not necessarily constrained at any moment to a single tuning system. This article discusses why a system using discrete piano pitches (not sliding pitches) chosen freely among the audible pitch continuum presents interesting musical and expressive possibilities. Audio and video of compositions and an improvisation exploiting the system demonstrate its potential and a performing interface for it.

Please see the Editorial Comment by Bethany L. Niell discussing this article. BACKGROUND. The success of adjunct breast cancer screening of women with dense breasts can be enhanced by identifying a...

One of the mutations in the microtubule-associated protein tau, P301S, is causative for dominantly inherited frontotemporal dementia characterized by extensive tau pathology for which no licensed treatment is available. Hydromethylthionine is a potent tau aggregation inhibitor. We report treatment of an asymptomatic carrier of the P301S mutation using hydromethylthionine over a 5-year period beginning at the mean age of onset of clinical decline in the family. During the period of treatment, the rates of progression of cerebral atrophy were reduced by 61%–66% in frontal and temporal lobes, and the patient remained clinically asymptomatic.

BackgroundSeveral previous studies have identified a continuity between childhood anxiety/withdrawal and anxiety disorder (AD) in later life. However, not all children with anxiety/withdrawal problems will experience an AD in later life. Previous studies have shown that the severity of childhood anxiety/withdrawal accounts for some of the variability in AD outcomes. However, no studies to date have investigated how variation in features of anxiety/withdrawal may relate to continuity prognoses. The present research addresses this gap.MethodsData were gathered as part of the Christchurch Health and Development Study, a 40-year population birth cohort of 1265 children born in Christchurch, New Zealand. Fifteen childhood anxiety/withdrawal items were measured at 7–9 years and AD outcomes were measured at various interviews from 15 to 40 years. Six network models were estimated. Two models estimated the network structure of childhood anxiety/withdrawal items independently for males and females. Four models estimated childhood anxiety/withdrawal items predicting adolescent AD (14–21 years) and adult AD (21–40 years) in both males and females.ResultsApproximately 40% of participants met the diagnostic criteria for an AD during both the adolescent (14–21 years) and adult (21–40 years) outcome periods. Outcome networks showed that items measuring social and emotional anxious/withdrawn behaviours most frequently predicted AD outcomes. Items measuring situation-based fears and authority figure-specific anxious/withdrawn behaviour did not consistently predict AD outcomes. This applied across both the male and female subsamples.ConclusionsSocial and emotional anxious/withdrawn behaviours in middle childhood appear to carry increased risk for AD outcomes in both adolescence and adulthood.

OBJECTIVE Previous research indicated that the International Committee of Medical Journal Editors guidelines of prospective trial registration with clearly identified primary and secondary outcome measures are only adhered to in 14.4% of studies published in the top five psychiatry journals between 1 January 2009 and 31 July 2013. This study examined if adherence has improved. METHODS The registration information, article information, primary outcome measures (POMs), participant numbers and funding source were extracted from studies published in the same five psychiatry journals between 1 January 2015 and 31 December 2019. Discrepancies between POMs in the articles and registry were tracked. RESULTS Of the 7268 publications, 268 studies required registration. Three (1.1%) were unregistered, 107 (39.9%) were retrospectively registered, and 158 (58.9%) were prospectively registered. Of the 158 prospectively registered studies, 16 (10.1%) had unclear POMs in the article or registration, 22 (13.9%) had discrepancies between registered and published POMs, and 33 (20.9%) had no POM discrepancies but had retrospectively updated POMs in the registry. Of the 22 studies with discrepancies, nine (40.9%) were determined to favour statistically significant results. Overall, 87 (32.5%) of the 268 studies were prospectively registered with no discrepancies between registered and published POMs and no changes to registered POMs or timeframes. CONCLUSION Although this rate of one third of published articles fully adhering to the guidelines is an improvement compared to previous research, further efforts still need to be made by both authors and journals to ensure full transparency in the reporting of studies in psychiatry.

The Cancer and Leukemia Group-B 9343 (CALGB 9343) trial demonstrated that women aged ≥ 70 years with early-stage breast cancer can safely omit radiation therapy (RT) and be treated with breast-conserving surgery (BCS) and adjuvant endocrine therapy (AET) alone. AET adherence is low, leaving an undertreated cohort who may be at increased risk of recurrence and death. We hypothesized that AET adherence and adjuvant treatment choice impact recurrence and survival among CALGB 9343 eligible women. SEER-Medicare was used to identify CALGB 9343 eligible women who underwent BCS between 2007 and 2016. Medicare claims were used to identify AET use, and the proportion of days covered by AET was used to categorize adherent (PDC ≥ 0.80) versus nonadherent patients (PDC

Objective: The term "Mauve factor" (pyrroluria) dates back to 1958 when Dr. Abram Hoffer defined the condition as elevated levels of pyrroles in the urine, currently called hydroxyhemepyrrolin-2-one (HPL). It was suggested that the raised pyrrole levels lead to depletions in zinc and vitamin B6, which, in turn, were hypothesized to result in a range of psychiatric disorders, such as schizophrenia, anxiety, and depression. Treatment implications are supplementation with zinc and B6. This article aimed to review the scientific literature associating pyrroluria with psychiatric symptoms, explore the validity of HPL testing, explore the role of nutrients as treatment options for pyrroluria, and discuss future research directions. Methods: A PRISMA review was conducted using search results from electronic databases PubMed, MEDLINE, PsycINFO, EMBASE from inception to February 2020 using the following keywords: hydroxyhemepyryrrolin (HPL), kryptopyrrole (KP), mauve factor, pyroluria, pyrroluria, monopyrroles. Article reference lists were also scanned and included where relevant. Results: Seventy-three articles were identified of which only three studies identified significantly higher HPL levels in a psychiatric population compared with controls, and there were no placebo-controlled treatment trials directed at pyrroluria. The other 13 clinical studies either showed no association or did not provide adequate data to show group differences in HPL levels. Despite an extensive history of practitioners diagnosing and treating a wide variety of mental health conditions associated with pyrroluria as well as clinical observations of elevated HPL being associated with psychiatric disorders, there was no clear research that showed the following: (1) elevated HPL is robustly associated with increased mental health symptoms, (2) elevated HPL in urine is associated with increased urine excretion of zinc and B6, and (3) high-dose zinc and B6 are an efficacious treatment for mental health problems associated with elevated HPL. Conclusions: Elevated HPL is a clinically observed, but poorly researched biomarker with unclear associations with mental disorders. Based on current evidence, HPL testing is not recommended as a screening or treatment tool. Further research is required in the following areas: establishment of which specific clinical populations exhibit elevated HPL, validation of the chemistry and validity of testing, and controlled trials to establish efficacy of high-dose zinc and B6 as treatment of elevated pyrroles.

Minji K Lee,1 Jennifer L St Sauver,1,2 Roger T Anderson,3 Mark Linzer,4 David T Eton1,2 1Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA; 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 3Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA; 4Hennepin Healthcare, Minneapolis, Minnesota, USA, University of Minnesota Medical School, Minneapolis, MN, USACorrespondence: Minji K LeeRobert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Harwick Building, Second Floor, 200 First St SW, Rochester, MN 55905, USATel +1 507 284 1310Email Lee.Minji@mayo.eduDavid T Eton Email eton.david@mayo.eduPurpose: To examine the factor structure and differential item functioning (DIF) of the Patient Experience with Treatment and Self-management (PETS version 2.0), a measure of treatment burden.Patients and Methods: Version 2.0 of the PETS has 60 items, extending the previously-validated 48-item version 1.0 by three domains (nine items) and three additional items in an existing domain. We conducted confirmatory factor analyses (CFA) on survey responses of 439 community-dwelling adults living with multiple chronic conditions who completed PETS version 2.0, using R packages, “lavaan” and “semTools.” We tested fit of second-order factors to explore simplifying the reporting of PETS scores. We examined DIF for the two second-order factors with “lordif” R package, testing groups by gender, education, and health literacy, using the McFadden pseudo R2 change criterion of ≥ 0.02 to flag items with DIF. Cronbach’s alpha and the intraclass correlation coefficient (ICC) were used to determine the reliability of PETS domains.Results: The first-order CFA model featuring 12 multi-item domains had an excellent fit (Comparative Fit Index [CFI]=0.989), as did the second-order CFA model (CFI=0.987), specifying two superordinate factors of treatment burden (workload and impact). Items in the workload and impact second-order factors did not show any DIF across gender, education, and health literacy groups as shown by McFadden pseudo R2 changes < 0.02. Cronbach’s alphas for all multi-item domain scales were ≥ 0.80, and ICCs of ten scales were ≥ 0.70, meeting the threshold for adequate test–retest reliability.Conclusion: Findings support the construct validity and reliability of PETS version 2.0. The fit of a factor model featuring superordinate (ie, second-order) factors of workload and impact supports index scoring that will simplify reporting of PETS scores. DIF analyses indicate that items from these indices can be interpreted in the same way, regardless of gender, education, or health literacy.Keywords: factor structure, patient-reported outcomes, multi-morbidity, psychometric testing, questionnaire, validation

Objectives: To provide advice and guidance regarding the management of mood disorders, derived from scientific evidence and supplemented by expert clinical consensus to formulate s that maximise clinical utility. Methods: Articles and information sourced from search engines including PubMed, EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (e.g. books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Relevant information was appraised and discussed in detail by members of the mood disorders committee, with a view to formulating and developing consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous consultation and external review involving: expert and clinical advisors, key stakeholders, professional bodies and specialist groups with interest in mood disorders. Results: The Royal Australian and New Zealand College of Psychiatrists mood disorders clinical practice guidelines 2020 (MDcpg2020) provide up-to-date guidance regarding the management of mood disorders that is informed by evidence and clinical experience. The guideline is intended for clinical use by psychiatrists, psychologists, primary care physicians and others with an interest in mental health care. Conclusion: The MDcpg2020 builds on the previous 2015 guidelines and maintains its joint focus on both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. Mood disorders committee: Gin S Malhi (Chair), Erica Bell, Darryl Bassett, Philip Boyce, Richard Bryant, Philip Hazell, Malcolm Hopwood, Bill Lyndon, Roger Mulder, Richard Porter, Ajeet B Singh and Greg Murray.

Background The results of the Cancer and Leukemia Group B (CALGB) 9343 trial showed that radiation therapy (RT) did not improve survival for women older than 70 y with early-stage estrogen receptor + breast cancer treated with breast conserving surgery and adjuvant endocrine therapy. In 2005, guidelines were modified to allow for RT omission; however, minimal change in clinical practice has occurred. The aim of this study was to determine if CALGB long-term follow-up data have affected RT utilization, and to characterize the population still receiving RT after breast conserving surgery. Methods The Surveillance, Epidemiology, and End Results–Medicare database was used to identify women diagnosed with early-stage breast cancer from 2004 to 2015 who matched the CALGB 9343 inclusion criteria. Multivariate logistic regression was carried out to identify the factors that affect the receipt of radiation therapy. We also plotted the overall use of RT over time juxtaposed with the temporal trends of CALGB 9343 clinical trial data, guideline recommendations, and publishing of long-term survival data. Results The study cohort included 25,723 Medicare beneficiaries, of whom 20,328 (79%) received RT and 5395 (21%) did not receive RT. In a multivariate model, the frequency of RT omission increased over time, with those diagnosed in year 2015 being 2.72 times more likely to omit RT compared with those diagnosed in 2004 (95% confidence interval 2.31-3.19). Conclusions This study investigated the impact of long-term CALGB 9343 data on clinical practice. The results of this study support results from previous studies, extend the dates of analysis, and indicate that after long-term follow-up of CALGB 9343 data, RT was less used, but overall trends did not dramatically decrease.

Incidence rates of hospital-presenting self-harm are highest in people under 25 years and are reportedly increasing in some countries. Intentional drug overdose (IDO) is the most common self-harm method among young people, with paracetamol the drug most frequently used. This study aimed to describe the characteristics, incidence, and temporal trends in paracetamol-related IDO among young people. Data from the National Self-Harm Registry Ireland on hospital-presenting self-harm by individuals aged 1024 years during 2007–2018 were examined. Annual IDO rates per 100,000 were calculated by age and gender. Joinpoint regression analyses and incidence rate ratios were used to examine trends in the incidence of paracetamol-related IDO. During the study, 10,985 paracetamol-related IDOs were recorded. The incidence of paracetamol-related IDO among young people increased by 9% between 2007 and 2018 (IRR 1.09 95% CI 1.00–1.19), with the highest annual percentage change (APC) in females aged 18–24 years (APC 1.2%). Conversely, rates of paracetamol-related IDO among males aged 18–24 years decreased significantly (APC 1.6%). Between 2013 and 2018, excesses of 386 and 151 paracetamol-related IDOs were observed in females aged 10–17 and 18–24 years, respectively, and 42 excess presentations were observed for males aged 10–17 years. There were 107 fewer presentations than expected for males aged 18–24 years. The increase in paracetamol-related IDO among specific groups of young people, particularly young females is an issue of growing concern. Interventions targeting IDO among young people are needed, incorporating measures to address the availability of paracetamol and aftercare following IDO.

Objective Usage of radiation among various surgical specialists has not been comprehensively evaluated. A systems-based analysis evaluating intraoperative radiation can help identify high use factors and dose reduction behaviors leading to quality improvement initiatives. Methods A retrospective review of all operative fluoroscopic-guided procedures from 2010 to 2017 from 4 hospitals in a tertiary academic health care system was performed. Results One thousand two hundred fifty-two cases were analyzed, and notable trends in metrics including type of equipment, procedures, surgical field, surgical specialty, and dose reduction techniques were demonstrated. Higher radiation exposures were correlated with fixed vs. mobile C-arm usage (1229 mGy vs. 331 mGy, P = .001), abdominal/pelvic procedures (429.2 mGy vs. 274.0 mGy, P = .002), and embolization (2450.6 mGy vs. 328.2 mGy, P = .019). Vascular surgery averaged 40 times higher radiation exposure per patient than other specialties (613.3 mGy vs. 15.6 mGy, P = .001). Notably, vascular surgeons utilized dose reduction techniques less frequently than urology (21.5% vs. 70%, P = .001) but more than neurosurgery and orthopedics (21.5% vs. 1.3% and 0%, P = .001, respectively). Conclusions A system-wide health care analysis identified vascular surgery procedures, use of a fixed C-arm, abdominal/pelvic procedures, and embolization cases as having the highest radiation exposure. These data can serve as baseline information for future quality improvement initiatives regarding fluoroscopy usage by surgeons.

OBJECTIVE. The purpose of this study was to quantify abdominal CT predictors of endoscopically refractory, uncontrolled variceal hemorrhage requiring portal venous intervention. MATERIALS AND METHODS. From 2009 to 2018, 64 patients with endoscopically refractory variceal hemorrhage requiring portal venous intervention (variceal hemorrhage group) and 67 patients without hemorrhage but with symptomatic, pressure gradient-proven portal hypertension (control group) underwent CT. CT scans were retrospectively reviewed for the following: varix size, variceal intraluminal protrusion, liver and spleen volumes, and portal vein diameter. RESULTS. Gastric variceal protrusion was found to be a strong CT parameter associated with refractory hemorrhage (mean depth, 0.75 mm in variceal hemorrhage group vs -2.91 mm in control group; p = 0.001). Gastric varix size was also associated with variceal hemorrhage (mean diameter, 8.03 vs 6.51 mm; p = 0.001). However, this trend was not observed in the sizes of the esophageal varices (mean diameter, 6.28 vs 6.43 mm; p = 0.370). Larger spleen volume (mean, 1312 vs 1152 cm3; p = 0.029) and liver volume (mean, 1514 vs 1143 cm3; p = 0.004) were also found to be predictors of variceal hemorrhage. Significant CT threshold findings included gastric variceal protrusion depth more than 0 mm (odds ratio [OR], 6.44), gastric varix size more than 6 mm (OR, 3.89), spleen volume more than 1000 cm3 (OR, 2.63), and liver volume more than 1000 cm3 (OR, 2.82). CONCLUSION. Quantitative imaging parameters on abdominal CT, such as intraluminal protrusion of gastric varices, gastric varix size, and larger spleen and liver volumes, were predictive of portal venous intervention, whereas esophageal varix size was not.

Background In primary care there is a need for more quality measures of person-centered outcomes, especially ones applicable to patients with multiple chronic conditions (MCCs). The aim of this study was to derive and validate a short-form version of the Patient Experience with Treatment and Self-management (PETS), an established measure of treatment burden, to help fill the gap in quality measurement. Methods Patient interviews (30) and provider surveys (30) were used to winnow items from the PETS (60 items) to a subset targeting person-centered care quality. Results were reviewed by a panel of healthcare providers and health-services researchers who finalized a pilot version. The Brief PETS was tested in surveys of 200 clinic and 200 community-dwelling MCC patients. Surveys containing the Brief PETS and additional measures (e.g., health status, medication adherence, quality of care, demographics) were administered at baseline and follow-up. Correlations and t-tests were used to assess validity, including responsiveness to change of the Brief PETS. Effect sizes (ES) were calculated on mean differences. Results Winnowing and panel review resulted in a 34-item Brief PETS pilot measure that was tested in the combined sample of 400 (mean age = 57.9 years, 50% female, 48% white, median number of conditions = 5). Reliability of most scales was acceptable (alpha > 0.70). Brief PETS scores were associated with age, income, health status, and quality of chronic illness care at baseline (P P P Conclusions The Brief PETS (final version: 32 items) is a reliable and valid tool for assessing person-centered care quality related to treatment burden. It holds promise as a means of giving voice to patient concerns about the complexity of disease management.

Background: The potential impact of the COVID-19 pandemic on population mental health is of increasing global concern. We examine changes in adult mental health in the UK population before and during the lockdown. Methods: In this secondary analysis of a national, longitudinal cohort study, households that took part in Waves 8 or 9 of the UK Household Longitudinal Study (UKHLS) panel, including all members aged 16 or older in April, 2020, were invited to complete the COVID-19 web survey on April 23–30, 2020. Participants who were unable to make an informed decision as a result of incapacity, or who had unknown postal addresses or addresses abroad were excluded. Mental health was assessed using the 12-item General Health Questionnaire (GHQ-12). Repeated cross-sectional analyses were done to examine temporal trends. Fixed-effects regression models were fitted to identify within-person change compared with preceding trends. Findings: Waves 6–9 of the UKHLS had 53 351 participants. Eligible participants for the COVID-19 web survey were from households that took part in Waves 8 or 9, and 17 452 (41·2%) of 42 330 eligible people participated in the web survey. Population prevalence of clinically significant levels of mental distress rose from 18·9% (95% CI 17·8–20·0) in 2018–19 to 27·3% (26·3–28·2) in April, 2020, one month into UK lockdown. Mean GHQ-12 score also increased over this time, from 11·5 (95% CI 11·3–11·6) in 2018–19, to 12·6 (12·5–12·8) in April, 2020. This was 0·48 (95% CI 0·07–0·90) points higher than expected when accounting for previous upward trends between 2014 and 2018. Comparing GHQ-12 scores within individuals, adjusting for time trends and significant predictors of change, increases were greatest in 18–24-year-olds (2·69 points, 95% CI 1·89–3·48), 25–34-year-olds (1·57, 0·96–2·18), women (0·92, 0·50–1·35), and people living with young children (1·45, 0·79–2·12). People employed before the pandemic also averaged a notable increase in GHQ-12 score (0·63, 95% CI 0·20–1·06). Interpretation: By late April, 2020, mental health in the UK had deteriorated compared with pre-COVID-19 trends. Policies emphasising the needs of women, young people, and those with preschool aged children are likely to play an important part in preventing future mental illness. Funding: None.

PURPOSE: The CALGB 9343 trial demonstrated that women age 70 or older with early-stage, ER+ breast cancer (BC) may safely forgo radiation therapy (RT) and be treated with breast conserving surgery (BCS) followed by adjuvant endocrine therapy (AET) alone. However, most patients in this population still undergo RT in part because AET adherence is low. We sought to develop a predictive model for AET initiation and adherence in order to improve decision-making with respect to RT omission. METHODS: Women ages 70 and older with early stage, ER+ BC were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidities, socioeconomic measures, prescription medications, and demographics were collected as potential predictors. Bivariate analysis was performed to identify factors associated with AET initiation and adherence. Stepwise selection of significant predictors was used to develop logistic-regression classifiers for initiation and adherence. Model performance was evaluated using the c-statistic and other measures. RESULTS: 11,037 patients met inclusion criteria. Within the cohort, 8,703 (78.9%) patients initiated AET and 6,685 (60.6%) were adherent to AET over one year. Bivariate predictors of AET initiation were similar to predictors of adherence. The best AET initiation and adherence classifiers were poorly predictive with c-statistics of 0.65 and 0.60, respectively. CONCLUSIONS: The best models in the present study were poorly predictive, demonstrating that the reasons for initiation and adherence to AET are complex and individual to the patient, and therefore difficult to predict. Initiation and adherence to AET are important factors in decision-making regarding whether or not to forgo adjuvant RT. In order to better formulate treatment plans for this population, future work should focus on improving individual prediction of AET initiation and adherence.

Objective: The International Classification of Diseases, 11th Revision classification of personality disorder removes all categories of disorder in favour of a single diagnostic spectrum extending from no personality dysfunction to severe personality disorder. Following concerns from some clinicians and Personality Disorder Societies, it was subsequently agreed to include a borderline pattern descriptor as a qualifier of the main diagnosis. We explore the value of this additional descriptor by examining personality data in patients with major depression. Method: We examined personality data obtained using the Structured Clinical Interview for Personality Disorder-II in 606 patients enrolled in five randomised controlled trials of depression. The Structured Clinical Interview for Personality Disorder-II uses the Diagnostic and Statistical Manual of Mental Disorders categorical system, which includes borderline personality disorder. The International Classification of Diseases, 11th Revision classification has five domain traits. Each of the Diagnostic and Statistical Manual of Mental Disorders personality disorder symptoms or behaviours from Structured Clinical Interview for Personality Disorder-II was reordered into the five domains independently by two assessors. The relationship between the two systems was examined by tabular and correlational analysis. Results: The findings showed that the symptoms of borderline personality disorder were associated with greater severity of personality disturbance in the International Classification of Diseases, 11th Revision classification ( p Conclusion: The addition of a borderline pattern descriptor is likely to add little to the International Classification of Diseases, 11th Revision classification of personality disorder. Its features are well represented within the severity/domain structure, which allows for more fine-grained description of the personality features that constitute the borderline concept.

Experimental data is required to estimate unknown parameters for a mathematical model describing thin film growth and to optimize the chemical vapor deposition (CVD) process. The most informative experimental data can be obtained by sequential model-based design of experiments (MBDoE), but this requires significant effort to implement compared to factorial design of experiments (DoE). For CVD processes it is not clear which approach is better or more efficient. Here, we compare the effectiveness of sequential A-optimal (MBDoE) with a factorial (DoE) using a case study involving a mechanistic model of thin-film deposition. The sequential A-optimal MBDoE and factorial DoE are compared based on their effectiveness in obtaining accurate parameter estimates and model predictions. Synthetic experimental data is generated from simulations with the true parameters plus noise. The results suggest that the A-optimal MBDoE is slightly better than factorial DoE for estimating model parameters. The parameter estimates from each experimental design approach are used to solve a model-based optimization problem. The results indicate that model-based optimization from the model with parameter estimates obtained by the A-optimal design gives a significantly better estimate of the optimal process conditions than factorial DoE.

Background Untreated antenatal depression and anxiety can be associated with short and long term health impacts on the pregnant woman, her infant and the rest of the family. Alternative interventions to those currently available are needed. This clinical trial aims to investigate the efficacy and safety of a broad-spectrum multinutrient formula as a treatment for symptoms of depression and anxiety in pregnant women and to determine the impact supplementation has on the general health and development of the infant. Methods This randomised, controlled trial will be conducted in Canterbury, New Zealand between April 2017 and June 2022. One hundred and twenty women aged over 16 years, between 12 and 24 weeks gestation and who score ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) will be randomly assigned to take the intervention (n = 60) or an active control formula containing iodine and riboflavin (n = 60) for 12 weeks. After 12 weeks, participants can enter an open-label phase until the birth of their infant and naturalistically followed for the first 12 months postpartum. Infants will be followed until 12 months of age. Randomisation will be computer-generated, with allocation concealment by opaque sequentially numbered envelopes. Participants and the research team including data analysts will be blinded to group assignment. The EPDS and the Clinical Global Impressions Scale of Improvement (CGI-I) will be the maternal primary outcome measures of this study and will assess the incidence of depression and anxiety and the improvement of symptomatology respectively. Generalized linear mixed effects regression models will analyse statistical differences between the multinutrient and active control group on an intent-to-treat basis. A minimum of a three-point difference in EPDS scores between the groups will identify clinical significance. Pregnancy outcomes, adverse events and side effects will also be monitored and reported. Discussion Should the multinutrient formula be shown to be beneficial for both the mother and the infant, then an alternative treatment option that may also improve the biopsychosocial development of their infants can be provided for pregnant women experiencing symptoms of depression and anxiety. Trial registration Trial ID: ACTRN12617000354381; prospectively registered at Australian New Zealand Clinical Trials Registry on 08/03/2017.

PURPOSE: The purpose of this study was to test the known-groups validity and responsiveness to change of the Patient Experience with Treatment and Self-management (PETS, vs. 2.0), a measure of treatment burden. METHODS: The PETS and other standard measures were mailed at baseline and 12-month follow-up to adults living with multiple chronic conditions in southeast Minnesota (USA). A sample of 365 people (mean age = 62.1 years) completed both surveys. Baseline, 12-month, and changes in PETS burden scores were examined. Clinical anchors used to test validity included number of diagnoses (2-4 vs. 5+), mental health diagnosis (yes/no), medication adherence and health literacy (suboptimal/optimal), and changes in self-efficacy, global physical and global mental health (worsening/improving). Independent samples t-tests were used to compare scores. RESULTS: PETS scales showed good internal consistency (alphas ≥ 0.80). There were few differences across number of diagnoses, but having a mental health diagnosis was associated with higher baseline PETS burden scores (Ps < .05). Suboptimal medication adherence and health literacy over time were associated with worse 12-month PETS burden scores (Ps < .05). Compared with improvements, declines over time in self-efficacy, global physical health, and global mental health were each associated with worsening change scores on PETS impact summary, medical expenses, and bother due to medication reliance and medication side effects (Ps < .05). CONCLUSION: Among multi-morbid adults, the PETS demonstrated evidence of known-groups validity and responsiveness to change across both objective (e.g., mental health diagnoses) and subjective anchors (e.g., changes in self-efficacy, global physical and mental health).

This article presents what is widely considered to be the best biographical account of the life of the controversial popular author, journalist and amateur spy, William Le Queux. The article originally appeared in Soldiers of the Queen, the journal of the Victorian Military Society, and is reproduced here with their kind permission in order to bring it before a new audience. It documents Le Queux’s life, from the little that is known about his early career through to his high-profile involvement in defence scaremongering before and during the First World War to his subsequent lapse into postwar obscurity.

BACKGROUND The purpose of this study was to estimate the proportion of Chinese cancer survivors experiencing financial hardship and then examine the relationship between material and behavioral financial hardship. METHODS This study surveyed 964 cancer survivors who were 30 to 64 years old and 644 survivors who were 65 years old or older during 2015-2016 (1608 survivors in all). Material financial hardship was measured by whether they had borrowed money because of cancer, its treatment, or the lasting effects of treatment, and behavioral financial hardship was measured by whether they had forgone some cancer-related medical care because of cost. Multivariable logistic regression models were used to examine factors associated with material financial hardship by age group. RESULTS Approximately 44% of the cancer survivors who were 65 years old or older borrowed money or went into debt because of cancer, and 54% of younger patients (P

Objectives We sought to identify and consider methodological issues that may have limited or confounded investigations into links between depression and acute coronary syndrome (ACS) events. Methods We reviewed salient research studies to identify such issues. Results Against previous conclusions, we found that lifetime depression is unlikely to have any primary ACS impact, while we clarify that ‘incident depression’ (depression commencing at variable periods around the time of the ACS event) appears to confer a greater risk than non-incident depression. As the time periods of incident depressions are likely to have quite differing causes, evaluating any consolidated risk period appears unwise. It remains unclear whether it is ‘depression’ that provides the risk for ACS events or a higher order factor. Variable use of depression measures and failure to evaluate depressive sub-types have further limited clarification. The response by ACS patients to antidepressant medication appears limited, and it remains to be determined whether exposure to an antidepressant might be a contributing factor. Finally, studies may have focused on an excessively refined association, and neglected to recognise that depression is associated with a wide range of vascular events, suggesting that a broader conceptual model may be required. Limitations The authors have considered only a limited set of studies in preparing this review, with the critique relying at times on subjective interpretation. Conclusions After decades of research pursuing links between depression and ACS events explanatory links remain obscure, presumably reflecting a range of methodological issues that we have discussed in this paper .

Using long-term survival data from the C9343 trial as a temporal reference point, this study aimed to determine radiation therapy (RT) treatment trends for older patients with early-stage breast cancer. The study also examined rates of adherence to adjuvant endocrine therapy (AET). The surveillance, epidemiology, and end results–medicare database was used to identify women with a diagnosis of breast cancer from 2007 through 2016. Bivariate associations were calculated to determine variable characteristics by time frame (group 1: 2007–2012 vs. group 2: 2013–2016). Multivariate logistic regression was used to estimate the effect of group on the RT use and AET adherence. The temporal rates for both RT and AET adherence over time were plotted. The final study cohort included 12,210 Medicare beneficiaries. Use of RT differed significantly between the groups, with a higher proportion omitting RT in the later period (25% of group 2 vs. 20% of group 1; p

Cardiovascular risk is associated with cognitive decline and this effect is attributed to brain pathology, including white matter hyperintensity (WMH) burden. Low-dose aspirin is frequently recommended for reducing vascular events. We investigated the effect of taking aspirin on the association between cardiovascular risk, WMH burden and cognitive function.The study sample was drawn from 318 dementia-free adults aged 67-71 years. Brain magnetic resonance imaging (MRI) scans were acquired from 239 participants.WMH total lesion volumes (TLV) were extracted using the automated lesion segmentation algorithm. We measured cardiovascular risk by calculating ASSIGN score. Cognitive ability was measured using a test of processing speed. We developed structural equation models to test our hypothesis.Sixty-eight participants (47.1 % male, mean age = 68.8 years) reported that they took aspirin. The demographic measures did not differ significantly by aspirin use. Among aspirin users, there was a strong negative association between WMH TLV and cognition (β = -0.43, p-value0.001), while in non-users of aspirin the only significant predictor of poorer cognition was cardiovascular risk (β = -0.17, p-value = 0.001).Aspirin use moderates the negative effect of WMH burden on cognition. Considering WMH burden in addition to cardiovascular risk could improve the prediction of cognitive decline in older adults with aspirin use.

Objective New breast screening modalities are being investigated to address the need for more sensitive breast cancer screening in women with dense breasts. We investigated the preferences and attitudes of these patients regarding adjunct screening modalities to help evaluate the acceptability of these exams. Methods In this institutional review board–approved prospective study, patients with dense breasts on their prior mammogram were invited to complete a survey. Patients were asked to estimate their personal breast cancer risk compared with peers, indicate their level of concern related to screening callbacks, radiation exposure, and intravenous (IV) contrast allergies, and identify which factors might deter them from getting adjunct screening exams. Results Five hundred eight patients with dense breasts presenting for screening mammography completed surveys. While most patients (304/508, 59.9%) felt it was likely or very likely that cancer could be missed on their mammogram, only 8.9% (45/508) had undergone adjunct screening exams in the past 3 years. The most commonly cited deterrents to adjunct screening were cost (340/508, 66.9%), pain (173/508, 34.1%), and concern that adjunct screening could lead to additional procedures (158/508, 31.1%). When asked to select among three hypothetical breast cancer screening modalities, patients strongly preferred the more sensitive examination, even if this involved greater cost (162/508, 31.9%) or IV-contrast administration (315/508, 62.0%). Conclusion Our data suggest that patients with dense breasts prefer adjunct screening exams that are both sensitive and inexpensive, although an increase in sensitivity could outweigh additional cost or even IV-line placement.

Background: Ambient air pollution affects neurological function, but its association with schizophrenia risk is unclear. We investigated exposure to nitrogen oxides (NOX) as a whole and nitrogen dioxide (NO2) specifically, as well as PM10, and PM2·5, during childhood and subsequent schizophrenia risk. Methods: People born in Denmark from 1980 to 1984 (N=230 844), who were residing in the country on their tenth birthday, and who had two Danish-born parents were followed-up from their tenth birthday until schizophrenia diagnosis or Dec 31, 2016. Mean daily exposure to each pollutant (NO2, NOX, PM10, and PM2·5) at all of an individual's residential addresses from birth to their tenth birthday was modelled. Incidence rate ratios, cumulative incidence, and population attributable risks were calculated using survival analysis techniques. Findings: We analysed data between Aug 1, 2018, and Nov 15, 2019. Of 230 844 individuals included, 2189 cohort members were diagnosed with schizophrenia during follow-up. Higher concentrations of residential NO2 and NOX exposure during childhood were associated with subsequent elevated schizophrenia risk. People exposed to daily mean concentrations of more than 26·5 μg/m3 NO2 had a 1·62 (95% CI 1·41–1·87) times increased risk compared with people exposed to a mean daily concentration of less than 14·5 μg/m3. The absolute risks of developing schizophrenia by the age of 37 years when exposed to daily mean concentrations of more than 26·5 μg/m3 NO2 between birth and 10 years were 1·45% (95% CI 1·30–1·62%) for men and 1·03% (0·90–1·17) for women, whereas when exposed to a mean daily concentration of less than 14·5 μg/m3, the risk was 0·80% (95% CI 0·69–0·92%) for men and 0·67% (0·57–0·79) for women. Associations between exposure to PM2·5 or PM10 and schizophrenia risk were less consistent. Interpretation: If the association between air pollution and schizophrenia is causal, reducing ambient air pollution including NO2 and NOX could have a potentially considerable effect on lowering schizophrenia incidence at the population level. Further investigations are necessary to establish a causal relationship. Funding: Lundbeck Foundation, Stanley Medical Research Institute, European Research Council, NordForsk, Novo Nordisk Foundation, National Health and Medical Research Council, Danish National Research Foundation.

BackgroundNatural disasters are increasing in frequency and impact; they cause widespread disruption and adversity throughout the world. The Canterbury earthquakes of 2010–2011 were devastating for the people of Christchurch, New Zealand. It is important to understand the impact of this disaster on the mental health of children and adolescents.AimsTo report psychiatric medication use for children and adolescents following the Canterbury earthquakes.MethodDispensing data from community pharmacies for the medication classes antidepressants, antipsychotics, anxiolytics, sedatives/hypnotics and methylphenidate are routinely recorded in a national database. Longitudinal data are available for residents of the Canterbury District Health Board (DHB) and nationally. We compared dispensing data for children and adolescents residing in Canterbury DHB with national dispensing data to assess the impact of the Canterbury earthquakes on psychotropic prescribing for children and adolescents.ResultsAfter longer-term trends and population adjustments are considered, a subtle adverse effect of the Canterbury earthquakes on dispensing of antidepressants was detected. However, the Canterbury earthquakes were not associated with higher dispensing rates for antipsychotics, anxiolytics, sedatives/hypnotics or methylphenidate.ConclusionsMental disorders or psychological distress of a sufficient severity to result in treatment of children and adolescents with psychiatric medication were not substantially affected by the Canterbury earthquakes.

OBJECTIVE To examine trends in uninsured rates between 2012 and 2016 among low-income adults aged RESEARCH DESIGN AND METHODS Data for 3,129 U.S. counties, obtained from the Small Area Health Insurance Estimates and Area Health Resources Files, were used to analyze trends in uninsured rates among populations with a household income ≤138% of the federal poverty level. Multivariable analysis adjusted for the percentage of county populations aged 50–64 years, the percentage of women, Distressed Communities Index value, and rurality. RESULTS In 2012, 39% of the population in the Diabetes Belt and 34% in non-Belt counties were uninsured (P < 0.001). In 2016 in states where Medicaid was expanded, uninsured rates declined rapidly to 13% in Diabetes Belt counties and to 15% in non-Belt counties. Adjusting for county demographic and economic factors, Medicaid expansion helped reduce uninsured rates by 12.3% in Diabetes Belt counties and by 4.9% in non-Belt counties. In 2016, uninsured rates were 15% higher for both Diabetes Belt and non-Belt counties in the nonexpansion states than in the expansion states. CONCLUSIONS ACA-driven Medicaid expansion was more significantly associated with reduced uninsured rates in Diabetes Belt than in non-Belt counties. Initial disparities in uninsured rates between Diabetes Belt and non-Belt counties have not existed since 2014 among expansion states. Future studies should examine whether and how Medicaid expansion may have contributed to an increase in the use of health services in order to prevent and treat diabetes in the Diabetes Belt.

Background Switching antidepressant medications is recommended when an initial antidepressant is not effective, when it is unable to be tolerated or when there are significant drug interactions. The aim of this paper is to review the evidence regarding when to switch antidepressants and the optimal approach to switching. Methods Clinical and academic experts in mood disorders from Australia and New Zealand (Treatment Algorithm Group, TAG) met to discuss the key considerations regarding switching antidepressants in the treatment of depression and formulate recommendations about switching strategies. Results While switching is recommended, there is limited data to guide on how best to approach switching antidepressants (e.g. whether to switch within class or out of class), and how to define the best time to consider switching. Broadly, switching within class after non-response is recommended for mild-moderate depression and out-of-class for patients with a more severe depression or melancholia. Limitations There is a limited evidence-base to draw on to make definitive recommendations on switching approaches. Conclusions Switching antidepressants is an appropriate strategy to use if there is a minimal response to an initial antidepressant. Further research is required to determine the optimal switching approach.

Background Studies conducted in the UK and in Ireland have reported increased rates of self-harm in adolescent females from around the time of the 2008 economic recession and through periods of subsequent national austerity programme implementation. It is not known if incidence rates have increased similarly in other Western European countries during this period. Methods Data from interlinked national administrative registers were extracted for individuals born in Denmark during 1981–2006. We estimated gender- and age-specific incidence rates (IRs) per 10,000 person-years at risk for hospital-treated non-fatal self-harm during 2000–2016 at ages 10–19 years. Results Incidence of self-harm peaked in 2007 (IR 25.1) and then decreased consistently year on year to 13.8 in 2016. This pattern was found in all age groups, in both males and females and in each parental income tertile. During the last 6 years of the observation period, 2011–2016, girls aged 13–16 had the highest incidence rates whereas, among boys, incidence was highest among 17–19 year olds throughout. Conclusions The temporal increases in incidence rates of self-harm among adolescents observed in some Western European countries experiencing major economic recession were not observed in Denmark. Restrictions to sales of analgesics, access to dedicated suicide prevention clinics, higher levels of social spending and a stronger welfare system may have protected potentially vulnerable adolescents from the increases seen in other countries. A better understanding of the specific mechanisms behind the temporal patterns in self-harm incidence in Denmark is needed to help inform suicide prevention in other nations.

New, non-chemical weed suppression methods are needed to support multi-tactic integrated weed management (IWM) programs that reduce reliance on herbicides. One such approach is to manage arbuscular mycorrhizal (AM) fungal communities to enhance their weed biocontrol. Successful implementation will require a better understanding of AM fungi-crop-weed relationships under field conditions, especially in the face of soil disturbances imposed by agricultural practices. We examined root AM fungal communities of four weed species and one model crop species (i.e., corn) in a field experiment with contrasting tillage and cover cropping treatments in Illinois, USA. Our objectives were to quantify the impact of AM fungi on the growth of corn and weed species, to assess influences of plant species, tillage, and cover cropping on AM fungal community structure, and to characterize the co-occurrence patterns of AM fungal taxa in weed and corn roots. Our results showed that effects of AM fungal taxa on corn and weed growth varied widely depending on plant species, and several AM fungal taxa had species-specific negative effects on weeds but not on corn. In addition, plant identity was the primary factor affecting root AM fungal community structure and co-occurrence patterns, whereas effects of tillage and cover cropping were relatively limited. We propose that AM fungal taxa that have selectively suppressive effects on weeds but not on corn are candidates for developing new strategies for weed biocontrol as part of IWM. Future approaches to weed management based on direct inoculation with AM fungal taxa or manipulation of AM fungal communities through specific management practices, are promising opportunities to increase the density of weed-suppressive AM fungal taxa in agroecosystems, and our methods provide important insights for AM fungal taxa selection.

Background The present study aimed to first describe the work‐related outcomes of cancer survivors and to then identify those characteristics that influenced the decision to stop working in rural China. Methods We assessed 752 cancer survivors (residents of rural areas, working at the time of diagnosis, >1 year since completing treatment) from the cross‐sectional study “China Survey of Experiences with Cancer”. Participants reported changes in employment status, income, and the ability to perform physical jobs due to cancer, as well as the work‐related outcomes of their informal caregivers. Logistic regression analyses were used to examine the association between sociodemographic characteristics, cancer characteristics, and changes in work (ie, continue to work vs not working). Results The participants were largely farmers (96%), women (56%), younger than 65 years old (69%), and diagnosed with colorectal (31%) and breast cancer (31%). Thirty‐nine percent reported reducing working hours, and 40% reported stopping work altogether. Approximately 7% of informal caregivers also stopped working in order to take care of those diagnosed with cancer. Thirty‐three percent of cancer survivors and 5% of their informal caregivers had no source of income following treatment. Controlling for other variables, lower educational attainment, physical limitations in work, and different cancer sites were significantly associated with ending employment in both men and women, while among men specifically, we observed that older age, being unmarried, and being diagnosed at later stages were significantly associated with an end to working. Conclusion Rural cancer survivors are at a high risk for stopping work after completing treatment, and many survivors and their caregivers experience poor work‐related outcomes and economic hardship. These results highlight the importance of paying attention to the work experiences of cancer survivors in rural China., The present study aimed to first describe the long‐term effects of cancer diagnosis and treatment on the work status of cancer survivors, and to then identify those characteristics that influenced the decision to stop working in rural China

Background: Many physical health problems are associated with elevated suicide risk whilst also providing access to means of overdose. We aimed to investigate whether psychiatric patients with physical co-morbidities who die by suicide were more likely than those without co-morbidities to self-poison with non-psychotropic medications. Methods: We analysed data on 14,648 psychiatric patients who died by suicide in England & Wales during 2004-2015, as recorded by the National Confidential Inquiry into Suicide and Safety in Mental Health. Using logistic regression models adjusted for age, gender, ethnicity, and primary drug dependence/misuse we compared patients diagnosed with physical co-morbidities versus those without to assess whether a greater proportion of the former had died by overdose, and medication prescribed to treat such disorders (e.g. opioids, insulin). Results: 24% (n=3525) were recorded as having physical co-morbidity. A greater proportion of these individuals died by self-poisoning than those without physical co-morbidity (37% vs. 20%, p

Background Older people are the fastest-growing demographic group among prisoners in England and Wales and they have complex health and social care needs. Their care is frequently ad hoc and uncoordinated. No previous research has explored how to identify and appropriately address the needs of older adults in prison. We hypothesised that the Older prisoner Health and Social Care Assessment and Plan (OHSCAP) would significantly increase the proportion of met health and social care needs 3 months after prison entry, compared to treatment as usual (TAU). Methods The study was a parallel randomised controlled trial (RCT) recruiting male prisoners aged 50 and over from 10 prisons in northern England. Participants received the OHSCAP or TAU. A clinical trials unit used minimisation with a random element as the allocation procedure. Data analysis was conducted blind to allocation status. The intervention group had their needs assessed using the OHSCAP tool and care plans were devised; processes that lasted approximately 30 min in total per prisoner. TAU included the standard prison health assessment and care. The intention to treat principle was followed. The trial was registered with the UK Clinical Research Network Portfolio (ISRCTN ID: 11841493) and was closed on 30 November 2016. Results Data were collected between 28 January 2014 and 06 April 2016. Two hundred and forty nine older prisoners were assigned TAU of which 32 transferred prison; 12 were released; 2 withdrew and 1 was deemed unsafe to interview. Two hundred and fifty three 3 prisoners were assigned the OHSCAP of which 33 transferred prison; 11 were released; 6 withdrew and 1 was deemed unsafe to interview. Consequently, data from 202 participants were analysed in each of the two groups. There were no significant differences in the number of unmet needs as measured by the Camberwell Assessment of Needs – Forensic Short Version (CANFOR-S). The mean number of unmet needs for the OHSCAP group at follow-up was 2.03 (SD = 2.07) and 2.06 (SD = 2.11) for the TAU group (mean difference = 0.088; 95% CI − 0.276 to 0.449, p = 0.621). No adverse events were reported. Conclusion The OHSCAP was fundamentally not implemented as planned, partly due to the national prison staffing crisis that ensued during the study period. Therefore, those receiving the OHSCAP did not experience improved outcomes compared to those who received TAU. Trial registration Current Controlled Trials: ISRCTN11841493, 25/10/2012.

For patients with diabetes, annual preventive care is essential to reduce the risk of complications. Local healthcare resources affect the utilization of diabetes preventive care. Our objectives were to evaluate the relative efficiency of counties in providing diabetes preventive care and explore potential to improve efficiencies. The study setting is public and private healthcare providers in US counties with available data. County-level demographics were extracted from the Area Health Resources File using data from 2010 to 2013, and individual-level information of diabetes preventive service use was obtained from the 2010 Behavioral Risk Factor Surveillance System. 1112 US counties were analyzed. Cluster analysis was used to place counties into three similar groups in terms of economic wellbeing and population characteristics. Group 1 consisted of metropolitan counties with prosperous or comfortable economic levels. Group 2 mostly consisted of non-metropolitan areas between distress and mid-tier levels, while Group 3 were mostly prosperous or comfortable counties in metropolitan areas. We used data enveopement analysis to assess efficiencies within each group. The majority of counties had modest efficiency in providing diabetes preventive care; 36 counties (57.1%), 345 counties (61.1%), and 263 counties (54.3%) were inefficient (efficiency scores

OBJECTIVE To examine the impact of a treatment package combining Interpersonal and Social Rhythm Therapy (IPSRT) and cognitive remediation (CR), vs IPSRT alone, on cognition, functioning, and mood disturbance outcomes in mood disorders. METHODS A pragmatic randomised controlled trial in adults with bipolar disorder (BD) or major depressive disorder (MDD), recently discharged from mental health services in Christchurch, New Zealand, with subjective cognitive difficulties. Individuals were randomised to a 12-month course of IPSRT with CR (IPSRT-CR), or without CR (IPSRT). In IPSRT-CR, CR was incorporated into therapy sessions from approximately session 5 and continued for 12 sessions. The primary outcome was change in Global Cognition (baseline to 12 months). RESULTS Sixty-eight individuals (BD n = 26, MDD n = 42; full/partial remission n = 39) were randomised to receive IPSRT-CR or IPSRT (both n = 34). Across treatment arms, individuals received an average of 23 IPSRT sessions. Change in Global Cognition did not differ between arms from baseline to treatment-end (12 months). Psychosocial functioning and longitudinal depression symptoms improved significantly more in the IPSRT compared with IPSRT-CR arm over 12 months, and all measures of functioning and mood symptoms showed moderate effect size differences favouring IPSRT (0.41-0.60). At 18 months, small to moderate, non-significant benefits (0.26-0.47) of IPSRT vs IPSRT-CR were found on functioning and mood outcomes. CONCLUSIONS Combining two psychological therapies to target symptomatic and cognitive/functional recovery may reduce the effect of IPSRT, which has implications for treatment planning in clinical practice and for CR trials in mood disorders.

BackgroundSurveillance of clinically treated self-harm episode frequency is an important component of suicide prevention in the dynamic context of COVID-19. Studies published to date have investigated the initial months following the onset of the pandemic, despite national and regional restrictions persisting to Summer 2021.MethodsWe conducted a descriptive time series analysis utilising data from the Greater Manchester Care Record, which contains de-identified, primary care health records of 2.8 million patients. Counts of incident and all episodes of self-harm recorded between 1st January 2019 and 31st May 2021 were made for all patients, with stratification by sex, age group, ethnicity, and index of multiple deprivation (IMD) quintile and examination of overall differences by national and regional restriction phases.FindingsBetween 1st January 2019 and 31st May 2021, 33,444 episodes of self-harm by 13,148 individuals were recorded. Frequency ratios of incident and all episodes of self-harm were 0.59 (95% CI 0.51 to 0.69) and 0.69 (CI 0.63 to 0.75) respectively in April 2020 compared to February 2020. Between August 2020 and May 2021 frequency ratios were 0.92 (CI 0.88 to 0.96) for incident episodes and 0.86 (CI 0.84 to 0.88) for all episodes compared to the same months in 2019. Reductions were largest among men and people living in the most deprived neighbourhoods. An increase in all-episode self-harm (frequency ratio 1.09, CI 1.03 to 1.16) was observed for adolescents aged 10-17 between August 2020 and May 2021.InterpretationThe COVID-19 pandemic has had a sustained impact on help seeking for self-harm. Reductions in primary care recorded self-harm have implications for clinicians’ ability to assess the needs and risks of individuals. Some patients may be experiencing prolonged untreated deterioration in their mental health while other groups are presenting in higher numbers. Our findings have important implications for primary care and mental health services in manging ongoing demand.FundingUKRI COVID-19 Rapid Response Initiative (grant reference COV0499), University of Manchester Presidential Fellowship (SS), and NIHR Greater Manchester Patient Safety Translational Research Centre.

Background Colorectal cancer (CRC) disparities vary by country and population group, but often have spatial features. This study of the United States state of Virginia assessed CRC outcomes, and identified demographic, socioeconomic and healthcare access contributors to CRC disparities. Methods County- and city-level cross-sectional data for 2011–2015 CRC incidence, mortality, and mortality-incidence ratio (MIR) were analyzed for geographically determined clusters (hotspots and cold spots) and their correlates. Spatial regression examined predictors including proportion of African American (AA) residents, rural-urban status, socioeconomic (SES) index, CRC screening rate, and densities of primary care providers (PCP) and gastroenterologists. Stationarity, which assesses spatial equality, was examined with geographically weighted regression. Results For incidence, one CRC hotspot and two cold spots were identified, including one large hotspot for MIR in southwest Virginia. In the spatial distribution of mortality, no clusters were found. Rurality and AA population were most associated with incidence. SES index, rurality, and PCP density were associated with spatial distribution of mortality. SES index and rurality were associated with MIR. Local coefficients indicated stronger associations of predictor variables in the southwestern region. Conclusions Rurality, low SES, and racial distribution were important predictors of CRC incidence, mortality, and MIR. Regions with concentrations of one or more factors of disparities face additional hurdles to improving CRC outcomes. A large cluster of high MIR in southwest Virginia region requires further investigation to improve early cancer detection and support survivorship. Spatial analysis can identify high-disparity populations and be used to inform targeted cancer control programming.

BACKGROUND: Excess deaths during the COVID-19 pandemic compared with those expected from historical trends have been unequally distributed, both geographically and socioeconomically. Not all excess deaths have been directly related to COVID-19 infection. We investigated geographical and socioeconomic patterns in excess deaths for major groups of underlying causes during the pandemic.METHODS: Weekly mortality data from 27/12/2014 to 2/10/2020 for England and Wales were obtained from the Office of National Statistics. Negative binomial regressions were used to model death counts based on pre-pandemic trends for deaths caused directly by COVID-19 (and other respiratory causes) and those caused indirectly by it (cardiovascular disease or diabetes, cancers, and all other indirect causes) over the first 30 weeks of the pandemic (7/3/2020-2/10/2020).FINDINGS: There were 62,321 (95% CI: 58,849 to 65,793) excess deaths in England and Wales in the first 30 weeks of the pandemic. Of these, 46,221 (95% CI: 45,439 to 47,003) were attributable to respiratory causes, including COVID-19, and 16,100 (95% CI: 13,410 to 18,790) to other causes. Rates of all-cause excess mortality ranged from 78 per 100,000 in the South West of England and in Wales to 130 per 100,000 in the West Midlands; and from 93 per 100,000 in the most affluent fifth of areas to 124 per 100,000 in the most deprived. The most deprived areas had the highest rates of death attributable to COVID-19 and other indirect deaths, but there was no socioeconomic gradient for excess deaths from cardiovascular disease/diabetes and cancer.INTERPRETATION: During the first 30 weeks of the COVID-19 pandemic there was significant geographic and socioeconomic variation in excess deaths for respiratory causes, but not for cardiovascular disease, diabetes and cancer. Pandemic recovery plans, including vaccination programmes, should take account of individual characteristics including health, socioeconomic status and place of residence.FUNDING: None.

There is widespread concern over the potential impact of the COVID-19 pandemic on suicide and self-harm globally, particularly in low- and middle-income countries (LMIC) where the burden of these behaviours is greatest. We synthesised the evidence from the published literature on the impact of the pandemic on suicide and self-harm in LMIC. This review is nested within a living systematic review (PROSPERO ID CRD42020183326) that continuously identifies published evidence (all languages) through a comprehensive automated search of multiple databases (PubMed; Scopus; medRxiv, PsyArXiv; SocArXiv; bioRxiv; the WHO COVID-19 database; and the COVID-19 Open Research Dataset by Semantic Scholar (up to 11/2020), including data from Microsoft Academic, Elsevier, arXiv and PubMed Central.) All articles identified by the 4th August 2021 were screened. Papers reporting on data from a LMIC and presenting evidence on the impact of the pandemic on suicide or self-harm were included. Methodological quality was assessed using an appropriate tool, and a narrative synthesis presented. A total of 22 studies from LMIC were identified representing data from 12 countries. There was an absence of data from Africa, the Pacific, and the Caribbean. The reviewed studies mostly report on the early months of COVID-19 and were generally methodologically poor. Few studies directly assessed the impact of the pandemic. The most robust evidence, from time-series studies, indicate either a reduction or no change in suicide and self-harm behaviour. As LMIC continue to experience repeated waves of the virus and increased associated mortality, against a backdrop of vaccine inaccessibility and limited welfare support, continued efforts are needed to track the indirect impact of the pandemic on suicide and self-harm in these countries.

Background Community treatment orders (CTOs) enable patients to be treated in the community rather than under detention in hospital. Population-based studies of suicide among patients subject to a CTO are scarce. Aims To compare suicide rates among patients subject to a CTO with all discharged psychiatric patients and those detained for treatment but not subject to a CTO at discharge (‘CTO-eligible’ patients). Method From a national case series of patients who died by suicide within 12 months of contact with mental health services in England during 2009–2018, we estimated average annual suicide rates for all discharged patients, those on a CTO at the time of suicide, those ever treated under a CTO and CTO-eligible patients. Results Suicide rates for patients on a CTO at the time of suicide (191.3 per 100 000 patients) were lower than all discharged patients (482.3 per 100 000 discharges). Suicide rates were similar in those ever treated under a CTO (350.1 per 100 000 CTOs issued) and in CTO-eligible patients (382.9 per 100 000 discharges). Suicide rates within 12 months of discharge were higher in persons ever under a CTO (205.1 per 100 000 CTOs issued) than CTO-eligible patients (161.5 per 100 000 discharges), but this difference was reversed for rates after 12 months of discharge (153.2 per 100 000 CTOs issued v. 223.4 per 100 000 discharges). Conclusions CTOs may be effective in reducing suicide risk. The relative benefits of CTOs and intensive aftercare may be time-dependent, with the benefit of a CTO being less before 12 months after discharge but greater thereafter. CTO utilisation requires a careful balancing of patient safety versus autonomy.

BackgroundDeaths in the first year of the COVID-19 pandemic in England & Wales have been shown to be unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups.MethodsYLL for registered deaths in England & Wales, from 27th December 2014 until 25th December 2020, were calculated using 2019 single year sex-specific life tables for England & Wales. Panel time-series models were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7th March 2020 and 25th December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease & diabetes, cancer, and other indirect deaths - all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group.FindingsBetween 7th March 2020 and 25th December 2020 there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England & Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from (916; 95% CI: 820 to 1,012) for the least deprived quintile to (1,645; 95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, an average of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, an average of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in both in the North West.InterpretationDuring 2020, the first calendar year of the COVID-19 pandemic, longstanding socioeconomic and geographical health inequalities in England & Wales were exacerbated, with the most deprived areas suffering the greatest losses in potential years of life lost.FundingNone

BackgroundMany studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages.MethodsWe followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices.ResultsEach indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93–1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71–0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67–0.87).ConclusionWe found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed.