A cost-of-illness analysis of the economic burden of obsessive-compulsive disorder in the United Kingdom.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition, with diagnosed patients typically experiencing moderate or severe symptoms. This study evaluated the cost-of-illness (CoI) of OCD in the UK, capturing the annual costs accrued to the National Health Service (NHS) and Personal Social Services (PSS), people with OCD, caregivers and society. METHODS: The UK OCD population was estimated and stratified by age group (children, adults, elderly), symptom severity (mild, moderate, severe) and treatment received (including no treatment). Costs for each subpopulation were estimated through a prevalence-based approach. Cost inputs were sourced from national databases, while additional inputs were informed by literature searches or expert clinician opinion. Scenario analyses explored other factors including comorbid depression treatment and presenteeism. RESULTS: The base-case analysis estimated a total annual CoI of £378,356,004 to the NHS, rising to £5,095,759,464 when a societal perspective was considered. The annual cost of care per person with OCD increased with severity (mild: £174; moderate: £365; severe: £902) due to increasing healthcare resource utilisation. The largest contributor to healthcare costs was cognitive behavioural therapy, while societal costs were driven by lost productivity through absenteeism. The base-case results likely underestimated the true economic burden of OCD; including comorbid depression led to a 132% increase in treatment costs, while presenteeism in people with OCD and lost productivity in caregivers amplified indirect costs. CONCLUSIONS: The economic burden of OCD in the UK is substantial and extends beyond direct treatment costs, highlighting a need for research into alternative treatments with greater efficacy.

Effects of exercise on obsessive-compulsive disorder symptoms: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis assessed the efficacy of exercise in reducing OCD symptoms. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, Scopus and grey literature until March 2022. The study was preregistered at Prospero (CRD42021283931). We included randomised controlled and pre-post trials assessing physical activity as an intervention for OCD. Risk of bias was assessed using the Cochrane ROBINS-I tool and the RoB2 tool. RESULTS: The analysis included 6 trials (N = 92); 2 were RCTS and 4 were pre-post design studies. A random-effects meta-analysis of pre-post data identified a large reduction of OCD symptoms following exercise (g = 1.33 [95%CI 1.06-1.61]; k = 6). Exercise was also associated with significant pre-post reductions in anxiety (g = 0.71 [95%CI 0.37-1.05; k = 4) and depression (g = 0.57 [95%CI 0.26-0.89]; k = 2). Risk of bias was moderate-high in uncontrolled trials on the ROBINS-I and RCTs showed 'some concerns' on the RoB2. CONCLUSION: Exercise was associated with a large pre-post reduction of OCD symptoms; however, few trials were of robust quality and all were at risk of bias. Further well-powered and better quality RCTs are required to assess the role of exercise as an intervention for OCD.KEY POINTSStudies exploring exercise as an adjunct therapy for OCD have small participant numbers, therefore a systematic review and meta-analysis is needed to estimate potential efficacy.Pre-post analysis shows that exercise was associated with a large reduction of OCD symptomsThe current systematic review and meta-analysis points to the potential for exercise to be beneficial for the treatment for OCD symptoms. However, more well-powered and better controlled RCTs are required to fully assess the benefit of exercise for the treatment of OCD symptoms.

Alkaptonuria.

Alkaptonuria is a rare inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase activity. The consequent homogentisic acid (HGA) accumulation in body fluids and tissues leads to a multisystemic and highly debilitating disease whose main features are dark urine, ochronosis (HGA-derived pigment in collagen-rich connective tissues), and a painful and severe form of osteoarthropathy. Other clinical manifestations are extremely variable and include kidney and prostate stones, aortic stenosis, bone fractures, and tendon, ligament and/or muscle ruptures. As an autosomal recessive disorder, alkaptonuria affects men and women equally. Debilitating symptoms appear around the third decade of life, but a proper and timely diagnosis is often delayed due to their non-specific nature and a lack of knowledge among physicians. In later stages, patients' quality of life might be seriously compromised and further complicated by comorbidities. Thus, appropriate management of alkaptonuria requires a multidisciplinary approach, and periodic clinical evaluation is advised to monitor disease progression, complications and/or comorbidities, and to enable prompt intervention. Treatment options are patient-tailored and include a combination of medications, physical therapy and surgery. Current basic and clinical research focuses on improving patient management and developing innovative therapies and implementing precision medicine strategies.

Clinical development innovation in rare diseases: overcoming barriers to successful delivery of a randomised clinical trial in alkaptonuria-a mini-review.

Alkaptonuria is a rare inherited disorder for which there was no disease-modifying treatment. In order to develop a successful approved therapy of AKU multiple barriers had to be overcome. These included activities before the conduct of the study including deciding on the drug therapy, the dose of the drug to be used, clarify the nature of the disease, develop outcome measures likely to yield a positive outcome, have a strategy to ensure appropriate patient participation through identification, build a consortium of investigators, obtain regulatory approval for proposed investigation plan and secure funding. Significant barriers were overcome during the conduct of the multicentre study to ensure harmonisation. Mechanisms were put in place to recruit and retain patients in the study. Barriers to patient access following completion of the study and regulatory approval were resolved.

Evaluation of Homogentisic Acid, a Prospective Antibacterial Agent Highlighted by the Suitability of Nitisinone in Alkaptonuria 2 (SONIA 2) Clinical Trial.

Despite urgent warnings about the spread of multidrug-resistant bacteria, the antibiotic development pipeline has remained sparsely populated. Naturally occurring antibacterial compounds may provide novel chemical starting points for antibiotic development programs and should be actively sought out. Evaluation of homogentisic acid (HGA), an intermediate in the tyrosine degradation pathway, showed that the compound had innate activity against Gram-positive and Gram-negative bacteria, which was lost following conversion into the degradation product benzoquinone acetic acid (BQA). Anti-staphylococcal activity of HGA can be attributed to effects on bacterial membranes. Despite an absence of haemolytic activity, the compound was cytotoxic to human HepG2 cells. We conclude that the antibacterial activity and in vitro safety profile of HGA render it more suitable for use as a topical agent or for inclusion in a small-molecule medicinal chemistry program.

Facing the "new normal": How adjusting to the easing of COVID-19 lockdown restrictions exposes mental health inequalities.

BACKGROUND: Re-establishing societal norms in the wake of the COVID-19 pandemic will be important for restoring public mental health and psychosocial wellbeing as well as economic recovery. We investigated the impact on post-pandemic adjustment of a history of mental disorder, with particular reference to obsessive-compulsive (OC) symptoms or traits. METHODS: The study was pre-registered (Open Science Framework; https://osf.io/gs8j2/). Adult members of the public (n = 514) were surveyed between July and November 2020, to identify the extent to which they reported difficulties re-adjusting as lockdown conditions eased. All were assessed using validated scales to determine which demographic and mental health-related factors impacted adjustment. An exploratory analysis of a subgroup on an objective online test of cognitive inflexibility was also performed. RESULTS: Adjustment was related to a history of mental disorder and the presence of OC symptoms and traits, all acting indirectly and statistically-mediated via depression, anxiety and stress; and in the case of OC symptoms, also via COVID-related anxiety (all p < 0.001). One hundred and twenty-eight (25%) participants reported significant adjustment difficulties and were compared with those self-identifying as "good adjusters" (n = 231). This comparison revealed over-representation of those with a history or family history of mental disorder in the poor adjustment category (all p < 0.05). 'Poor-adjusters' additionally reported higher COVID-related anxiety, depression, anxiety and stress and OC symptoms and traits (all p < 0.05). Furthermore, history of mental disorder directly statistically mediated adjustment status (p < 0.01), whereas OC symptoms (not OC traits) acted indirectly via COVID-related anxiety (p < 0.001). Poor-adjusters also showed evidence of greater cognitive inflexibility on the intra-extra-dimensional set-shift task. CONCLUSION: Individuals with a history of mental disorder, OC symptoms and OC traits experienced greater difficulties adjusting after lockdown-release, largely statistically mediated by increased depression, anxiety, including COVID-related anxiety, and stress. The implications for clinical and public health policies and interventions are discussed.

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD).

BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). METHODS: The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning. DISCUSSION: We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial. TRIAL REGISTRATION: ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021.

Early intervention for obsessive compulsive disorder: An expert consensus statement.

Obsessive-compulsive disorder (OCD) is common, emerges early in life and tends to run a chronic, impairing course. Despite the availability of effective treatments, the duration of untreated illness (DUI) is high (up to around 10 years in adults) and is associated with considerable suffering for the individual and their families. This consensus statement represents the views of an international group of expert clinicians, including child and adult psychiatrists, psychologists and neuroscientists, working both in high and low and middle income countries, as well as those with the experience of living with OCD. The statement draws together evidence from epidemiological, clinical, health economic and brain imaging studies documenting the negative impact associated with treatment delay on clinical outcomes, and supporting the importance of early clinical intervention. It draws parallels between OCD and other disorders for which early intervention is recognized as beneficial, such as psychotic disorders and impulsive-compulsive disorders associated with problematic usage of the Internet, for which early intervention may prevent the development of later addictive disorders. It also generates new heuristics for exploring the brain-based mechanisms moderating the 'toxic' effect of an extended DUI in OCD. The statement concludes that there is a global unmet need for early intervention services for OC related disorders to reduce the unnecessary suffering and costly disability associated with under-treatment. New clinical staging models for OCD that may be used to facilitate primary, secondary and tertiary prevention within this context are proposed.