As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases1–3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Implementation of CBT and FI is poor, particularly for FI. Reasons for poor implementation and service implications are discussed.

Objectives To evaluate the effectiveness of integrated motivational interviewing and cognitive behavioural therapy in addition to standard care for patients with psychosis and a comorbid substance use problem.Design Two centre, open, rater blind randomised controlled trial.Setting Secondary care in the United Kingdom.Participants 327 patients with a clinical diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a diagnosis of dependence on or misuse of drugs, alcohol, or both according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.Intervention The intervention was integrated motivational interviewing and cognitive behavioural therapy plus standard care, which was compared with standard care alone. Phase one of therapy—“motivation building”—concerns engaging the patient, then exploring and resolving ambivalence for change in substance use. Phase two—“action”—supports and facilitates change using cognitive behavioural approaches. Up to 26 therapy sessions were delivered over one year.Main outcome measures The primary outcome was death from any cause or admission to hospital in the 12 months after completion of therapy. Secondary outcomes were frequency and amount of substance use (assessed using the timeline followback method), readiness to change, perceived negative consequences of use, psychotic symptom ratings, number and duration of relapses, and global assessment of functioning and deliberate self harm at 12 and 24 months, with additional timeline followback assessments at 6 and 18 months. Analysis was by intention to treat and robust treatment effect estimates were produced.Results 327 participants were randomly allocated to either the intervention (n=164) or treatment as usual (n=163). At 24 months, 326 (99.7%) were assessed on the primary outcome and 246 (75.2%) on the main secondary outcomes. Treatment had no beneficial effect on hospital admissions or death during follow-up, with 23.3% (38/163) of the therapy group and 20.2% (33/163) of controls deceased or admitted (adjusted odds ratio 1.16, 95% confidence interval 0.68 to 1.99; P=0.579). Therapy had no effect on the frequency of substance use or the perceived negative consequences of misuse, but did have a statistically significant effect on amount used per substance using day (adjusted ORs for main substance 1.50, 95% CI 1.08 to 2.09; P=0.016; and all substances 1.48, 95% CI 1.07 to 2.05; P=0.017). Treatment had a statistically significant effect on readiness to change use at 12 months (adjusted OR 2.05, 95% CI 1.26 to 3.31; P=0.004) that was not maintained at 24 months (0.78, 95% CI 0.48 to 1.28; P=0.320). There were no effects of treatment on clinical outcomes such as relapses, psychotic symptoms, functioning, and self harm.Conclusions Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and substance misuse do not improve outcome in terms of hospitalisation, symptom outcomes, or functioning. This approach does reduce the amount of substance use...

Relapse of psychosis is common and has profound adverse consequences. Early signs interventions assume that timely prediction of relapse allows preventative action to reduce the chance of full relapse. The utility of early signs in this context is critically reviewed. Cohort studies suggest that early signs (e.g. anxiety, insomnia) appear in the few weeks before relapse and have modest predictive validity (sensitivity 10%-80%, median 61%; specificity 38%-100%, median 81%), indicating that accuracy of relapse prediction needs improvement. Trials using early signs to target interventions show that targeted antipsychotic medication is less effective than adequately dosed maintenance medication but relapse rates are lower than when intervention is delayed until relapse. The relative value of more complex interventions including psycho-education and relapse prevention strategies is not yet clearly established because there are few trials, some with important design limitations. Basic symptoms are subtle, subjective, qualitative changes in experience claimed to precede psychosis. One retrospective cohort study and studies of "at risk mental states'" transition to psychosis indicate some predictive validity. We suggest that basic symptoms are potentially valuable additions to the range of early signs and deserve further investigation in the effort to enhance the predictive validity of the early signs syndrome.

Background Schizophrenia relapses are common, have profound, adverse consequences for patients and are costly to health services. Early signs interventions aim to use warning signs of deterioration to prevent full relapse. Such interventions show promise but could be further developed. This study addresses 2 developments: adding basic symptoms to checklists of conventional early signs and using a mobile phone app ExPRESS to aid early signs monitoring. Objective This study aimed to (1) design a pool of self-report items assessing basic symptoms (Basic Symptoms Checklist, BSC); (2) develop and beta test a mobile phone app (ExPRESS) for monitoring early signs, basic symptoms, and psychotic symptoms; and (3) evaluate the long-term acceptability of ExPRESS via qualitative feedback from participants in a 6-month feasibility study. Methods The BSC items and ExPRESS were developed and then adjusted following feedback from beta testers (n=5) with a schizophrenia diagnosis. Individuals (n=18) experiencing a relapse of schizophrenia within the past year were asked to use ExPRESS for 6 months to answer weekly questions about experiences of early signs, basic symptoms, and psychotic symptoms. At the end of follow-up, face-to-face qualitative interviews (n=16; 2 were uncontactable) explored experiences of using ExPRESS. The topic guide sought participants’ views on the following a priori themes regarding app acceptability: item content, layout, and wording; app appearance; length and frequency of assessments; worries about app use; how app use fitted with participants’ routines; and the app’s extra features. Interview transcripts were analyzed using the framework method, which allows examination of both a priori and a posteriori themes, enabling unanticipated aspects of app use experiences to be explored. Results Participants’ mean age was 38 years (range 22-57 years). Responses to a priori topics indicated that long-term use of ExPRESS was acceptable; small changes for future versions of ExPRESS were suggested. A posteriori themes gave further insight into individuals’ experiences of using ExPRESS. Some reported finding it more accessible than visits from a clinician, as assessments were more frequent, more anonymous, and did not require the individual to explain their feelings in their own words. Nevertheless, barriers to app use (eg, unfamiliarity with smartphones) were also reported. Despite ExPRESS containing no overtly therapeutic components, some participants found that answering the weekly questions prompted self-reflection, which had therapeutic value for them. Conclusions This study suggests that apps are acceptable for long-term symptom monitoring by individuals with a schizophrenia diagnosis across a wide age range. If the potential benefits are unders...