Costs of UK community care for individuals with recessive dystrophic epidermolysis bullosa: Findings of the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin fragility disorder requiring multidisciplinary management. Information regarding costs of current standard treatment is scant. Objectives: As part of a longitudinal natural history study, we explored the community care costs of UK patients with different forms of RDEB. Methods: Fifty-nine individuals with RDEB provided detailed information on multiple facets of RDEB including disease severity scores (iscorEB, BEBS) and patient reported outcomes (quality of life evaluation in epidermolysis bullosa, iscorEB patient questionnaire). Costs data included time spent doing dressings, frequency of dressing changes, details of materials used, and paid and unpaid care. Results: Overall costs of dressing materials and associated care were high in RDEB. Median annual costs across all subtypes for those using dressings (n = 51) were over £26 000. For severe RDEB (RDEB-S), median costs were almost £90 000 per annum, with a median of 18 h per week spent on dressing changes. Half of working-age adults with RDEB were unemployed and 39% of carers were unable to take on full-time or part-time paid employment, adding to indirect costs and the financial burden from RDEB on families and society. Conclusions: The findings demonstrate the high costs of care of RDEB, particularly for RDEB-S. The current expense supports the drive to develop new therapies which accelerate wound healing and diminish total wound burden, thereby reducing costs of dressings and care. While costly to bring to market, these might ultimately reduce the overall cost of treatment and also the impact on individuals living with this rare disease. The data also highlight the need for adequate reimbursement for EB care which can place significant financial strain on families.

Carbon footprint of hospital laundry: a life-cycle assessment.

OBJECTIVES: To assess greenhouse gas (GHG) emissions from a regional hospital laundry unit, and model ways in which these can be reduced. DESIGN: A cradle to grave process-based attributional life-cycle assessment. SETTING: A large hospital laundry unit supplying hospitals in Southwest England. POPULATION: All laundry processed through the unit in 2020-21 and 2021-22 financial years. PRIMARY OUTCOME MEASURE: The mean carbon footprint of processing one laundry item, expressed as in terms of the global warming potential over 100 years, as carbon dioxide equivalents (CO2e). RESULTS: Average annual laundry unit GHG emissions were 2947 t CO2e. Average GHG emissions were 0.225 kg CO2e per item-use and 0.5080 kg CO2e/kg of laundry. Natural gas use contributed 75.7% of on-site GHG emissions. Boiler electrification using national grid electricity for 2020-2022 would have increased GHG emissions by 9.1%, however by 2030 this would reduce annual emissions by 31.9% based on the national grid decarbonisation trend. Per-item transport-related GHG emissions reduce substantially when heavy goods vehicles are filled at ≥50% payload capacity. Single-use laundry item alternatives cause significantly higher per-use GHG emissions, even if reusable laundry were transported long distances and incinerated at the end of its lifetime. CONCLUSIONS: The laundry unit has a large carbon footprint, however the per-item GHG emissions are modest and significantly lower than using single-use alternatives. Future electrification of boilers and optimal delivery vehicle loading can reduce the GHG emissions per laundry item.

Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.

The health care cost of comorbidity in individuals with mental disorders: A Danish register-based study.

AIM: The aim of the study was to estimate the annual health care cost by number of comorbid mental and somatic disorders in persons with a mental disorder. METHODS: All persons living in Denmark between 2004 and 2017 with a hospital diagnosis of a mental disorder were identified. We investigated the cost of different health care services: psychiatric hospitals, somatic hospitals, primary health care (e.g. general practitioners, psychologists and so on) and subsidised prescriptions. Within those with at least one mental disorder, we examined the costs for people with (a) counts of different types of mental disorders (e.g. exactly 1, exactly 2 and so on up to 8 or more) and (b) counts of different types of somatic disorders (e.g. no somatic disorders, exactly 1, exactly 2 and so on up to 15 or more). The estimates are reported in average cost per case and nationwide annual cost in Euro 2017. RESULTS: In total, 447,209 persons (238,659 females and 208,550 males) were diagnosed with at least one mental disorder in the study period. The average annual health care cost per case and nationwide cost was 4471 Euros and 786 million Euro, respectively, for persons with exactly one mental disorder, and 33,273 Euro and 3.6 million Euro for persons with eight or more mental disorders. The annual health care cost was 4613 Euro per case and 386 million Euro for persons without any somatic disorders, while the cost per case was 16,344 Euro and 0.7 million Euro in nationwide cost for persons with 15 or more disorders. The amount and proportion of the different health care costs varied by type of comorbidity and count of disorders. CONCLUSIONS: The annual health care cost per case was higher with increasing number of comorbid mental and somatic disorders, while the nationwide annual health care cost was lower with increasing number of comorbid disorders for persons with a mental disorder in Denmark.

Current issues and future considerations for the wider implementation of robotic-assisted surgery: a qualitative study.

OBJECTIVES: The effective implementation of a fast-changing healthcare delivery innovation, such as robotic-assisted surgery (RAS), into a healthcare system, can be affected (both positively and negatively) by external contextual factors. As part of a wider project investigating ways to optimise the implementation of RAS, this qualitative study aimed to uncover current issues of RAS and predictions about the future of robotic surgery. We refer to 'current issues' as the topical and salient challenges and opportunities related to the introduction of RAS in the UK healthcare system, from the perspectives of key stakeholders involved in the delivery and implementation of RAS. DESIGN: Semi-structured interviews and focus groups were conducted. A thematic analysis was conducted to summarise salient issues that were articulated by the participants. SETTING AND PARTICIPANTS: The interview sample (n=35) comprised surgeons, wider theatre staff and other relevant personnel involved in the introduction and delivery of RAS services across the UK, including service managers and policymakers/commissioners. Two focus groups were also conducted with surgical trainees (n=7) and members of the public (n=8), respectively. RESULTS: The results revealed a largely positive attitude towards the introduction of RAS technology and an expectation of continued rapid expansion. Areas perceived to be particularly pertinent and requiring ongoing attention were also highlighted, including the need to achieve improved quality control, expertise quantification and training issues and the need to educate the public. Issues of centralisation, service organisation and equity of access were also emphasised. CONCLUSIONS: Our study has highlighted a range of issues perceived to be particularly pertinent to the current and future provision of RAS which should be addressed. The areas outlined can enable healthcare managers and surgeons to plan for the adoption and/or expansion of RAS services.

Photodynamic versus white-light-guided resection of first-diagnosis non-muscle-invasive bladder cancer: PHOTO RCT.

BACKGROUND: Around 7500 people are diagnosed with non-muscle-invasive bladder cancer in the UK annually. Recurrence following transurethral resection of bladder tumour is common, and the intensive monitoring schedule required after initial treatment has associated costs for patients and the NHS. In photodynamic diagnosis, before transurethral resection of bladder tumour, a photosensitiser that is preferentially absorbed by tumour cells is instilled intravesically. Transurethral resection of bladder tumour is then conducted under blue light, causing the photosensitiser to fluoresce. Photodynamic diagnosis-guided transurethral resection of bladder tumour offers better diagnostic accuracy than standard white-light-guided transurethral resection of bladder tumour, potentially reducing the chance of subsequent recurrence. OBJECTIVE: The objective was to assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis-guided transurethral resection of bladder tumour. DESIGN: This was a multicentre, pragmatic, open-label, parallel-group, non-masked, superiority randomised controlled trial. Allocation was by remote web-based service, using a 1 : 1 ratio and a minimisation algorithm balanced by centre and sex. SETTING: The setting was 22 NHS hospitals. PARTICIPANTS: Patients aged ≥ 16 years with a suspected first diagnosis of high-risk non-muscle-invasive bladder cancer, no contraindications to photodynamic diagnosis and written informed consent were eligible. INTERVENTIONS: Photodynamic diagnosis-guided transurethral resection of bladder tumour and standard white-light cystoscopy transurethral resection of bladder tumour. MAIN OUTCOME MEASURES: The primary clinical outcome measure was the time to recurrence from the date of randomisation to the date of pathologically proven first recurrence (or intercurrent bladder cancer death). The primary health economic outcome was the incremental cost per quality-adjusted life-year gained at 3 years. RESULTS: We enrolled 538 participants from 22 UK hospitals between 11 November 2014 and 6 February 2018. Of these, 269 were allocated to photodynamic diagnosis and 269 were allocated to white light. A total of 112 participants were excluded from the analysis because of ineligibility (n = 5), lack of non-muscle-invasive bladder cancer diagnosis following transurethral resection of bladder tumour (n = 89) or early cystectomy (n = 18). In total, 209 photodynamic diagnosis and 217 white-light participants were included in the clinical end-point analysis population. All randomised participants were included in the cost-effectiveness analysis. Over a median follow-up period of 21 months for the photodynamic diagnosis group and 22 months for the white-light group, there were 86 recurrences (3-year recurrence-free survival rate 57.8%, 95% confidence interval 50.7% to 64.2%) in the photodynamic diagnosis group and 84 recurrences (3-year recurrence-free survival rate 61.6%, 95% confidence interval 54.7% to 67.8%) in the white-light group (hazard ratio 0.94, 95% confidence interval 0.69 to 1.28; p = 0.70). Adverse event frequency was low and similar in both groups [12 (5.7%) in the photodynamic diagnosis group vs. 12 (5.5%) in the white-light group]. At 3 years, the total cost was £12,881 for photodynamic diagnosis-guided transurethral resection of bladder tumour and £12,005 for white light. There was no evidence of differences in the use of health services or total cost at 3 years. At 3 years, the quality-adjusted life-years gain was 2.094 in the photodynamic diagnosis transurethral resection of bladder tumour group and 2.087 in the white light group. The probability that photodynamic diagnosis-guided transurethral resection of bladder tumour was cost-effective was never > 30% over the range of society's cost-effectiveness thresholds. LIMITATIONS: Fewer patients than anticipated were correctly diagnosed with intermediate- to high-risk non-muscle-invasive bladder cancer before transurethral resection of bladder tumour and the ratio of intermediate- to high-risk non-muscle-invasive bladder cancer was higher than expected, reducing the number of observed recurrences and the statistical power. CONCLUSIONS: Photodynamic diagnosis-guided transurethral resection of bladder tumour did not reduce recurrences, nor was it likely to be cost-effective compared with white light at 3 years. Photodynamic diagnosis-guided transurethral resection of bladder tumour is not supported in the management of primary intermediate- to high-risk non-muscle-invasive bladder cancer. FUTURE WORK: Further work should include the modelling of appropriate surveillance schedules and exploring predictive and prognostic biomarkers. TRIAL REGISTRATION: This trial is registered as ISRCTN84013636. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 40. See the NIHR Journals Library website for further project information.

Around 7500 people are diagnosed with early-stage bladder cancer in the UK each year. Early bladder cancer is contained within the bladder and has not yet invaded the bladder's muscle wall or spread elsewhere in the body. The cancer will return (recur) in around half of people after initial treatment and they have to attend hospital for regular check-ups, with costs to both them and the NHS. The first step in treating early bladder cancer is surgery to remove the tumour. This surgery is normally performed under white light. Photodynamic diagnosis is a new technique in which a liquid is put into the patient's bladder before surgery and a blue light is used during the operation. This causes the bladder cancer to fluoresce so that it can be seen more easily by the surgeon. The Photodynamic versus white-light-guided resection of first diagnosis non-muscle-invasive bladder cancer ( PHOTO ) trial aimed to find out whether or not using photodynamic diagnosis at initial surgery would reduce how often the cancer recurred and whether or not this could reduce the cost of treating early bladder cancer. A total of 538 people with early bladder cancer who had a medium to high chance of their cancer returning after treatment were enrolled in the PHOTO trial. They were included in one of two treatment groups, at random: 269 had photodynamic surgery and 269 had standard white-light surgery. People in both groups were monitored regularly for any recurrences, with further treatment as appropriate. After 3 years, 4 out of 10 people in each group had a recurrence of their bladder cancer. We found no difference between the treatment groups in the number of people with recurrences. We found no evidence of a benefit to patients, and the total costs of photodynamic surgery were higher than those of standard white light. We therefore recommend that it is no longer used in the treatment of this group of patients.

Temporal changes in sex- and age-specific incidence profiles of mental disorders-A nationwide study from 1970 to 2016.

OBJECTIVE: Information on mental disorders over time is critical for documenting changes in population burden, and aiding understanding of potential causal and non-causal factors. The aim of this study was to provide temporal changes in the sex- and age-specific incidence rates (IR) of mental disorders diagnosed in Danish hospitals during five decades and investigate whether such changes may be attributable to changes in administrative reporting practice. METHODS: This population-based cohort study included all people living in Denmark between 1970 and 2016. Mental disorders diagnoses were obtained from the Danish Psychiatric Central Research Register. We estimated the IR of each mental disorder (all persons, and sex- and age-specific IRs) and examined the impact of two administrative changes. RESULTS: Our study included 9 107 157 people, followed for 233.0 million person-years. During follow-up, 9.5% were diagnosed with at least one mental disorder. The IR for any mental disorder was 39.0 per 10,000 person-years. Despite fluctuations, this increased between 1970-84 and 2005-2016, from 28.9 to 63.0 per 10,000 person-years. Increases were most pronounced for younger age groups. Administrative changes did appear to influence incidence rates. CONCLUSION: Mental disorder IRs have increased in Denmark since 1970, with age of diagnosis shifting downwards. Both trends were likely impacted by administrative changes, while the latter is likely to be (partly) attributable to earlier detection and increased reporting of child-onset conditions. Our findings may provide valuable context of the epidemiology of mental disorders across age groups for comparison with other studies and populations.

Critical analysis of quality of life and cost-effectiveness of enhanced recovery after surgery (ERAS) for patient's undergoing urologic oncology surgery: a systematic review.

PURPOSE: Enhanced recovery after surgery (ERAS) protocols have been implemented across a variety of disciplines to improve outcomes. Herein we describe the impact of ERAS on quality of life (QOL) and cost for patients undergoing urologic oncology surgery. METHODS: A systematic literature search using the MEDLINE, Scopus, Clinictrials.gov, and Cochrane Review databases for studies published between 1946 and 2020 was conducted. Articles were reviewed and assigned a risk of bias by two authors and were included if they addressed ERAS and either QOL or cost-effectiveness for patients undergoing urologic oncology surgery. RESULTS: The literature search yielded a total of 682 studies after removing duplicates, of which 10 (1.5%) were included in the review. Nine articles addressed radical cystectomy, while one addressed ERAS and QOL for laparoscopic nephrectomy. Six publications assessed the impact of ERAS on QOL domains. Questionnaires used for assessment of QOL varied across studies, and timing of administration was heterogeneous. Overall, ERAS improved patient QOL during early phases of recovery within the realms of bowel function, physical/social/cognitive functioning, sleep and pain control. Costs were assessed in 4 retrospective studies including 3 conducted in the United States and one from China all addressing radical cystectomy. Studies demonstrated either decreased costs associated with ERAS as a result of decreased length of stay or no change in cost based on ERAS implementation. CONCLUSION: While limited studies are published on the subject, ERAS implementation for radical cystectomy and laparoscopic nephrectomy improved patient-reported QOL during early phases of recovery. For radical cystectomy, there was a decreased or neutral overall financial cost associated with ERAS. Further studies assessing QOL and cost-effectiveness over the entire global period of care in a variety of urologic oncology surgeries are warranted.

The development of the Cystectomy-Pathway Assessment Tool (C-PAT): a concise tool to assess the quality of care in the cystectomy pathway.

OBJECTIVES: To develop and test the psychometric properties of a concise, patient-reported questionnaire, designed to assess key aspects of the radical cystectomy (RC) patient pathway that are important to both patients and clinicians. PATIENTS AND METHODS: Draft items were developed by a consultation with a 13-member expert clinical panel, and the in-depth qualitative analysis of 14 semi-structured interviews with patients who had received RC within the previous 18 months. A further nine cognitive interviews with patients refined the items and ensured they were easy to complete. Pilot testing in 122 patients recruited from five hospitals in England tested the properties of validity and reliability of the resulting 17-item questionnaire. RESULTS: Patients and clinicians identified the following aspects as important for the delivery of quality patient care. These included timely referral and initial test results; an explanation of risk/benefits of treatment; access to a cancer nurse specialist; training and support in stoma management; timely surgery, surgical complications, and timely follow-up. Pilot testing showed missing data was low (≤3% for all items), and between 73% and 89% of the responses to items were the most positive about their care (indicating ceiling effects). Five items were identified using factor analysis as being statistically related (Cronbach's α 0.76, intraclass correlation coefficient test-retest reliability of 0.95) and formed the scored part of the tool 'care and support', scored 0-16. There was insufficient evidence at this stage to show the tool was capable of measuring differences between cancer centres. CONCLUSION: We have developed a questionnaire that captures aspects of quality of care within the RC patient pathway. The results support the validity and reliability of the 17-item Cystectomy-Pathway Assessment Tool (C-PAT). We envisage the tool can be the basis for audit of the patient reported assessment of the quality of care for individual cancer centres.

The cost of mental disorders in Denmark: a register-based study.

The aim of the study was to undertake a detailed analysis of healthcare cost, public transfer payments, and income loss associated with a broad range of mental disorders in Denmark. Based on all persons living in Denmark, we identified those with a hospital diagnosis of one of 18 types of mental disorders and 10 age- and sex-matched controls per case. For each mental disorder, the outcomes were nationwide totals, cost per case, and cost per capita, investigated by sex, age strata, and the number of years after diagnosis. We found a substantial annual income loss of 5 billion Euros and excess healthcare cost of 1 billion Euros for persons with any mental disorder. Each mental disorder was associated with an income loss, excess healthcare cost, and excess public transfer payments compared to matched controls. An interactive data visualisation site with summary data is available at https://nbepi.com/cost .

A Randomized Trial of PHOTOdynamic Surgery in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Recurrence of non­muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumor (TURBT). Photodynamic diagnosis (PDD) provides better diagnostic accuracy and more complete tumor resection and may reduce recurrence. However, there is limited evidence on the longer-term clinical effectiveness and cost-effectiveness of PDD-guided resection. METHODS: In this pragmatic, open-label, parallel-group randomized trial conducted in 22 U.K. National Health Service hospitals, we recruited participants with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence on the basis of routine visual assessment before being listed for TURBT. Participants were assigned (1:1) to PDD-guided TURBT or to standard white light (WL)­guided TURBT. The primary clinical outcome was time to recurrence at 3 years of follow-up, analyzed by modified intention to treat. RESULTS: A total of 538 participants were enrolled (269 in each group), and 112 participants without histologic confirmation of NMIBC or who had had cystectomy were excluded. After 44 months' median follow-up, 86 of 209 in the PDD group and 84 of 217 in the WL group had recurrences. The hazard ratio for recurrence was 0.94 (95% confidence interval [CI], 0.69 to 1.28; P=0.70). Three-year recurrence-free rates were 57.8% (95% CI, 50.7 to 64.2) and 61.6% (95% CI, 54.7 to 67.8) in the PDD and WL groups, respectively, with an absolute difference of −3.8 percentage points (95% CI, −13.37 to 5.59) favoring PDD. Adverse events occurred in less than 2% of participants, and rates were similar in both groups, as was health-related quality of life. PDD-guided TURBT was £876 (95% CI, −766 to 2518; P=0.591) more costly than WL-guided TURBT over a 3-year follow-up, with no evidence of a difference in quality-adjusted life years (−0.007; 95% CI, −0.133 to 0.119; P=0.444). CONCLUSIONS: PDD-guided TURBT did not reduce recurrence rates, nor was it cost-effective compared with WL at 3 years. (Funded by the National Institute for Health and Care Research Health Technology Assessment program; ISRCTN number, ISRCTN84013636.)

Disparities in multiple sleep characteristics among non-Hispanic White and Hispanic/Latino adults by birthplace and language preference: cross-sectional results from the US National Health Interview Survey.

OBJECTIVE: To investigate whether sleep disparities vary by birthplace among non-Hispanic White (NHW) and Hispanic/Latino adults in the USA and to investigate language preference as an effect modifier. DESIGN: Cross-sectional. SETTING: USA. PARTICIPANTS: 254 699 men and women. METHODS: We used pooled 2004-2017 National Health Interview Survey data. Adjusting for sociodemographic and behavioural/clinical characteristics, survey-weighted Poisson regressions with robust variance estimated prevalence ratios (PRs) and 95% CIs of self-reported sleep characteristics (eg, sleep duration, trouble staying asleep) among (1) foreign-born NHW adults and Hispanic/Latino heritage groups versus US-born NHW adults and (2) Hispanic/Latino heritage groups versus foreign-born NHW adults. We further stratified by language preference in comparisons of Hispanic/Latino heritage groups with the US-born NHW group. RESULTS: Among 254 699 participants with a mean age±SE 47±0.9 years, 81% self-identified their race/ethnicity as NHW, 12% Mexican, 2% Puerto Rican, 1% Cuban, 1% Dominican and 3% Central/South American. Compared with US-born NHW adults, foreign-born NHW adults were more likely to report poor sleep quality (eg, PRtrouble staying asleep=1.27 (95% CI: 1.17 to 1.37)), and US-born Mexican adults were no more likely to report non-recommended sleep duration while foreign-born Mexican adults were less likely (eg, PR≤5-hours=0.52 (0.47 to 0.57)). Overall, Mexican adults had lower prevalence of poor sleep quality versus US-born NHW adults, and PRs were lowest for foreign-born Mexican adults. US-born Mexican adults were more likely than foreign-born NHW adults to report shorter sleep duration. Regardless of birthplace, Puerto Rican adults were more likely to report shorter sleep duration versus NHW adults. Generally, sleep duration and quality were better among Cuban and Dominican adults versus US-born NHW adults but were similar versus foreign-born NHW adults. Despite imprecision in certain estimates, Spanish language preference was generally associated with increasingly better sleep among Hispanic/Latino heritage groups compared with US-born NHW adults. CONCLUSION: Sleep disparities varied by birthplace, Hispanic/Latino heritage and language preference, and each characteristic should be considered in sleep disparities research.

Register-based metrics of years lived with disability associated with mental and substance use disorders: a register-based cohort study in Denmark.

BACKGROUND: Mental disorders account for a substantial proportion of the years lived with disability (YLDs) globally. These estimates have generally been calculated top down based on summary statistics. The aim for this study was to calculate YLDs and a novel related measure, Health Loss Proportion (HeLP), for 18 mental and substance use disorders, based on person-level register data (bottom up). METHODS: A cohort of 6 989 627 Danish residents (5·9% had a diagnosis of a mental or substance use disorder registered in the Danish Psychiatric Central Research Register) was investigated. YLDs (the duration of disease multiplied by a disability weight) were calculated for the disorder of interest and for comorbid mental and substance use disorders. HeLPs were estimated as YLDs associated with an index disorder and comorbid mental and substance use disorders divided by person-years at risk in persons with the index disorder. All analyses were adjusted for mental and substance use comorbidity using a multiplicative model of disability weights. FINDINGS: Major depressive disorder was the most prevalent disorder, although schizophrenia was the leading cause of YLDs in both sexes combined (YLDs 273·3 [95 % CI 232·3-313·6] per 100 000 person-years). People diagnosed with schizophrenia lost the equivalent of 73% (63-83%) of healthy life per year due to mental and substance use disorders, the largest HeLP of all mental and substance use disorders. Comorbidity of mental and substance use disorders accounted for 69-83% of HeLPs in people with either cannabis use disorders, other drug use disorder and ADHD. By contrast, comorbidity explained 11-23% of the HeLPs in people with autism spectrum disorders, conduct disorder, and schizophrenia. INTERPRETATION: Substantial variation in disability was observed across age, sex, and disorders. The new HeLP metric provides novel details of the contribution of comorbidity to the disability associated with mental and substance use disorders. FUNDING: The Danish National Research Foundation, Queensland Government Department of Health, European Union's Horizon 2020, Lundbeck Foundation, Stanley Medical Research Institute. TRANSLATION: For the Danish translation of the abstract see Supplementary Materials section.

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial.

INTRODUCTION: Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. METHODS: A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. PRIMARY OUTCOME: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. ETHICS AND DISSEMINATION: Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03763253; ISCRTN58401737.

Risk of Early-Onset Depression Associated With Polygenic Liability, Parental Psychiatric History, and Socioeconomic Status.

Importance: Combining information on polygenic risk scores (PRSs) with other known risk factors could potentially improve the identification of risk of depression in the general population. However, to our knowledge, no study has estimated the association of PRS with the absolute risk of depression, and few have examined combinations of the PRS and other important risk factors, including parental history of psychiatric disorders and socioeconomic status (SES), in the identification of depression risk. Objective: To assess the individual and joint associations of PRS, parental history, and SES with relative and absolute risk of early-onset depression. Design, Setting, and Participants: This case-cohort study included participants from the iPSYCH2012 sample, a case-cohort sample of all singletons born in Denmark between May 1, 1981, and December 31, 2005. Hazard ratios (HRs) and absolute risks were estimated using Cox proportional hazards regression for case-cohort designs. Exposures: The PRS for depression; SES measured using maternal educational level, maternal marital status, and paternal employment; and parental history of psychiatric disorders (major depression, bipolar disorder, other mood or psychotic disorders, and other psychiatric diagnoses). Main Outcomes and Measures: Hospital-based diagnosis of depression from inpatient, outpatient, or emergency settings. Results: Participants included 17 098 patients with depression (11 748 [68.7%] female) and 18 582 (9429 [50.7%] male) individuals randomly selected from the base population. The PRS, parental history, and lower SES were all significantly associated with increased risk of depression, with HRs ranging from 1.32 (95% CI, 1.29-1.35) per 1-SD increase in PRS to 2.23 (95% CI, 1.81-2.64) for maternal history of mood or psychotic disorders. Fully adjusted models had similar effect sizes, suggesting that these risk factors do not confound one another. Absolute risk of depression by the age of 30 years differed substantially, depending on an individual's combination of risk factors, ranging from 1.0% (95% CI, 0.1%-2.0%) among men with high SES in the bottom 2% of the PRS distribution to 23.7% (95% CI, 16.6%-30.2%) among women in the top 2% of PRS distribution with a parental history of psychiatric disorders. Conclusions and Relevance: This study suggests that current PRSs for depression are not more likely to be associated with major depressive disorder than are other known risk factors; however, they may be useful for the identification of risk in conjunction with other risk factors.

Development and validation of a recommended checklist for assessment of surgical videos quality: the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool.

INTRODUCTION: There has been a constant increase in the number of published surgical videos with preference for open-access sources, but the proportion of videos undergoing peer-review prior to publication has markedly decreased, raising questions over quality of the educational content presented. The aim of this study was the development and validation of a standard framework for the appraisal of surgical videos submitted for presentation and publication, the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool. METHODS: An international committee identified items for inclusion in the LAP-VEGaS video assessment tool and finalised the marking score utilising Delphi methodology. The tool was finally validated by anonymous evaluation of selected videos by a group of validators not involved in the tool development. RESULTS: 9 items were included in the LAP-VEGaS video assessment tool, with every item scoring from 0 (item not presented in the video) to 2 (item extensively presented in the video), with a total marking score ranging from 0 to 18. The LAP-VEGaS video assessment tool resulted highly accurate in identifying and selecting videos for acceptance for conference presentation and publication, with high level of internal consistency and generalisability. CONCLUSIONS: We propose that peer review in adherence to the LAP-VEGaS video assessment tool could enhance the overall quality of published video outputs.

Alcohol-attributed disease burden in four Nordic countries between 2000 and 2017: Are the gender gaps narrowing? A comparison using the Global Burden of Disease, Injury and Risk Factor 2017 study.

INTRODUCTION AND AIMS: The gender difference in alcohol use seems to have narrowed in the Nordic countries, but it is not clear to what extent this may have affected differences in levels of harm. We compared gender differences in all-cause and cause-specific alcohol-attributed disease burden, as measured by disability-adjusted life-years (DALY), in four Nordic countries in 2000-2017, to find out if gender gaps in DALYs had narrowed. DESIGN AND METHODS: Alcohol-attributed disease burden by DALYs per 100 000 population with 95% uncertainty intervals were extracted from the Global Burden of Disease database. RESULTS: In 2017, all-cause DALYs in males varied between 2531 in Finland and 976 in Norway, and in females between 620 in Denmark and 270 in Norway. Finland had the largest gender differences and Norway the smallest, closely followed by Sweden. During 2000-2017, absolute gender differences in all-cause DALYs declined by 31% in Denmark, 26% in Finland, 19% in Sweden and 18% in Norway. In Finland, this was driven by a larger relative decline in males than females; in Norway, it was due to increased burden in females. In Denmark, the burden in females declined slightly more than in males, in relative terms, while in Sweden the relative decline was similar in males and females. DISCUSSION AND CONCLUSIONS: The gender gaps in harm narrowed to a different extent in the Nordic countries, with the differences driven by different conditions. Findings are informative about how inequality, policy and sociocultural differences affect levels of harm by gender.

Sleep Health and Serious Psychological Distress: A Nationally Representative Study of the United States among White, Black, and Hispanic/Latinx Adults.

PURPOSE: Prior studies investigating the relationship between sleep and serious psychological distress (SPD) have lacked racial/ethnic diversity and generalizability. We investigated associations between sleep and SPD among a large, nationally representative, and racially/ethnically diverse sample of US adults. METHODS: We pooled cross-sectional data from the 2004 to 2017 National Health Interview Survey. Participants self-reported sleep duration and sleep disturbances (eg, trouble falling and staying asleep). SPD was defined as a Kessler Psychological Distress Scale (K6) score ≥13. Adjusting for sociodemographic, health behavior, and clinical characteristics, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) of SPD for each sleep characteristic, overall and by race/ethnicity. RESULTS: Among 316,840 participants, the mean age ± standard error was 46.9 ± 0.1 years, 52% were women, 75% were non-Hispanic (NH)-White, 16% NH-Black, and 9% Hispanic/Latinx. The prevalence of SPD was 3.4% for NH-Whites, 4.1% for NH-Blacks, and 4.5% for Hispanics/Latinxs. Participants with <7 hours versus 7-9 hours of sleep duration were more likely to have SPD, and the magnitude of the association was strongest among NH-Black participants (PRNH-Blacks=3.50 [95% CI: 2.97-4.13], PR Hispanics/Latinx=2.95 [2.42-3.61], and PRNH-Whites=2.66 [2.44-2.89]). Positive associations between sleep disturbances and SPD were generally stronger among NH-Black and Hispanic/Latinx compared to NH-White adults. CONCLUSION: Poor sleep health was positively associated with SPD, and the magnitude of the association was generally stronger among racial/ethnic minorities. Future investigations should prospectively focus on the determinants and health consequences of SPD attributable to objectively measured sleep across racial/ethnic groups.

Urodynamics tests for the diagnosis and management of bladder outlet obstruction in men: the UPSTREAM non-inferiority RCT.

BACKGROUND: Lower urinary tract symptoms (LUTS) in men may indicate bladder outlet obstruction (BOO) or weakness, known as detrusor underactivity (DU). Severe bothersome LUTS are a common indication for surgery. The diagnostic tests may include urodynamics (UDS) to confirm whether BOO or DU is the cause, potentially reducing the number of people receiving (inappropriate) surgery. OBJECTIVES: The primary objective was to determine whether a care pathway including UDS is no worse for symptom outcome than one in which it is omitted, at 18 months after randomisation. Rates of surgery was the key secondary outcome. DESIGN: This was a pragmatic, multicentre, two-arm (unblinded) randomised controlled trial, incorporating a health economic analysis and qualitative research. SETTING: Urology departments of 26 NHS hospitals in England. PARTICIPANTS: Men (aged ≥ 18 years) seeking further treatment, potentially including surgery, for bothersome LUTS. Exclusion criteria were as follows: unable to pass urine without a catheter, having a relevant neurological disease, currently undergoing treatment for prostate or bladder cancer, previously had prostate surgery, not medically fit for surgery and/or unwilling to be randomised. INTERVENTIONS: Men were randomised to a care pathway based on non-invasive routine tests (control) or routine care plus invasive UDS (intervention arm). MAIN OUTCOME MEASURES: The primary outcome was International Prostate Symptom Score (IPSS) at 18 months after randomisation and the key secondary outcome was rates of surgery. Additional secondary outcomes included adverse events (AEs), quality of life, urinary and sexual symptoms, UDS satisfaction, maximum urinary flow rate and cost-effectiveness. RESULTS: A total of 820 men were randomised (UDS, 427; routine care, 393). Sixty-seven men withdrew before 18 months and 11 died (unrelated to trial procedures). UDS was non-inferior to routine care for IPSS 18 months after randomisation, with a confidence interval (CI) within the margin of 1 point (-0.33, 95% CI -1.47 to 0.80). A lower surgery rate in the UDS arm was not found (38% and 36% for UDS and routine care, respectively), with overall rates lower than expected. AEs were similar between the arms at 43-44%. There were more cases of acute urinary retention in the routine care arm. Patient-reported outcomes for LUTS improved in both arms and satisfaction with UDS was high in men who received it. UDS was more expensive than routine care. From a secondary care perspective, UDS cost an additional £216 over an 18-month time horizon. Quality-adjusted life-years (QALYs) were similar, with a QALY difference of 0.006 in favour of UDS over 18 months. It was established that UDS was acceptable to patients, and valued by both patients and clinicians for its perceived additional insight into the cause and probable best treatment of LUTS. LIMITATIONS: The trial met its predefined recruitment target, but surgery rates were lower than anticipated. CONCLUSIONS: Inclusion of UDS in the diagnostic tests results in a symptom outcome that is non-inferior to a routine care pathway, but does not affect surgical rates for treating BOO. Results do not support the routine use of UDS in men undergoing investigation of LUTS. FUTURE WORK: Focus should be placed on indications for selective utilisation of UDS in individual cases and long-term outcomes of diagnosis and therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56164274. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 42. See the NIHR Journals Library website for further project information.

After hospital referral, men with bothersome lower urinary tract symptoms (LUTS) are assessed with standard tests. These include measurement of urine flow rate, bladder diaries and questionnaires, including the International Prostate Symptom Score (IPSS). UPSTREAM (Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods) researched whether or not including an extra test, urodynamics (UDS), helps when considering treatment options. UDS is a more invasive test and measures pressure in the bladder to check whether or not the prostate is causing obstruction. It was presumed that, if there is no obstruction, surgery would not be offered, so that using UDS would reduce the number of prostate operations. Each man participating (820 in total) was assessed with the standard tests. Around half of them had no extra tests (the 'routine care' arm of the trial); the rest had the UDS tests (the 'UDS' arm). Men then went on to have treatment, which they chose having discussed their test results with a urologist. IPSS and other symptom scores were examined for each man 18 months after joining the trial. At 18 months, surgery outcomes were known for 792 men and IPSS was known for 669 men. We investigated if the two trial arms showed similar changes in the IPSS and if there were fewer operations done in the UDS arm. We identified similar reductions in the IPSS in both arms. However, UDS tests did not reduce the number of operations. Analysing all the costs, it was found that a pathway including UDS costs more than routine care. Interviews were conducted that showed that men found UDS acceptable, and that the additional information helped both the men and their doctors consider which treatment would be most appropriate. These results do not support the routine use of UDS in the assessment of every man considering prostate surgery for LUTS. Further exploration of the data may identify circumstances in which UDS could be helpful.