Use of cognitive remediation to treat negative symptoms in schizophrenia: is it time yet?

Cognitive remediation is currently recommended to treat cognitive and functional impairments in patients with schizophrenia. Recently, treatment of negative symptoms has been proposed as a new target for cognitive remediation. Evidence of reductions in negative symptoms has been described in different meta-analyses. However, treating primary negative symptoms is still an open question. Despite some emerging evidence, more research focused on individuals with primary negative symptoms is indispensable. In addition, more attention to the role of moderators and mediators and the use of more specific assessments is necessary. Nevertheless, cognitive remediation could be considered as one promising option to treat primary negative symptoms.

The effects of collaborative care versus consultation liaison for anxiety disorders and depression in Denmark: two randomised controlled trials.

BACKGROUND: Collaborative care (CC) and consultation liaison (CL) are two conceptual models aiming to improve mental healthcare in primary care. The effects of these models have not been compared in a Danish setting. AIMS: To examine the effects of CC versus CL for persons with anxiety and depression in Danish general practices (trial registration: NCT03113175 and NCT03113201). METHOD: Two randomised parallel superiority trials for anxiety disorders and depression were carried out in 2018-2019. In the CC-group, care managers collaborated with general practitioners (GPs) to provide evidence-based treatment according to structured treatment plans. They followed up and provided psychoeducation and/or cognitive-behavioural therapy. The GPs initiated pharmacological treatment if indicated, and a psychiatrist provided supervision. In the CL-group, the intervention consisted of the GP's usual treatment. However, the psychiatrist and care manager could be consulted. Primary outcomes were depression symptoms (Beck Depression Inventory-II, BDI-II) in the depression trial and anxiety symptoms (Beck Anxiety Inventory, BAI) in the anxiety trial at 6-month follow-up. RESULTS: In total, 302 participants with anxiety disorders and 389 participants with depression were included. A significant difference in BDI-II score was found in the depression trial, with larger symptom reductions in the CC-group (CC: 12.7, 95% CI 11.4-14.0; CL: 17.5, 95% CI 16.2-18.9; Cohen's d = -0.50, P ≤ 0.001). There was a significant difference in BAI in the anxiety trial (CC: 14.9, 95% CI 13.5-16.3; CL: 17.9, 95% CI 16.5-19.3; Cohen's d = -0.34, P ≤ 0.001), with larger symptom reductions in the CC-group. CONCLUSIONS: Collaborative care was an effective model to improve outcomes for persons with depression and anxiety disorders.

Clinical and cost-effectiveness of social recovery therapy for the prevention and treatment of long-term social disability among young people with emerging severe mental illness (PRODIGY): randomised controlled trial.

BACKGROUND: Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention. AIMS: We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone. METHOD: A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16-25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation. RESULTS: We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was -4.44 (95% CI -10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm. CONCLUSIONS: We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.

Long-term follow-up of a randomised controlled trial of prolonged exposure therapy and supportive counselling for post-traumatic stress disorder in adolescents: a task-shifted intervention.

BACKGROUND: Empirical evidence on the longer-term effectiveness of evidence-based treatments for adolescents with post-traumatic stress disorder (PTSD) in low-resource settings is needed. The aim of the study was to evaluate the maintenance of treatment gains achieved in a comparative study of effectiveness of prolonged exposure therapy for adolescents (PE-A) and supportive counselling (SC) in adolescents with PTSD up to 24-months post-treatment. METHOD: Sixty-three adolescents (13-18 years) with PTSD were randomly assigned to receive either of the interventions comprising 7-14 sessions of treatment provided by trained and supervised non-specialist health workers (NSHWs). The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale, at pretreatment, post-treatment, and at 3-, 6-, 12- and 24-months post-treatment follow-up (FU) evaluations. RESULTS: Participants in both the prolonged exposure and SC treatment groups attained a significant reduction in PTSD symptoms and maintained this reduction in PTSD symptoms at 12- and 24-month assessment. Participants receiving prolonged exposure experienced greater improvement on the PTSD symptom severity scale than those receiving SC at 12-months FU [difference in PE-A v. SC mean scores = 9.24, 95% CI (3.66-14.83), p < 0.001; g = 0.88] and at 24-months FU [difference in PE-A v. SC mean scores = 9.35, 95% CI (3.53-15.17), p = 0.002; g = 0.68]. CONCLUSIONS: Adolescents with PTSD continued to experience greater benefit from prolonged exposure treatment than SC provided by NSHWs in a community setting 12 and 24 months after completion of treatment.

Longitudinal relationships between cognition and functioning over 2 years in euthymic patients with bipolar disorder: a cross-lagged panel model approach with the FACE-BD cohort.

BACKGROUND: Longitudinal studies of the relationship between cognition and functioning in bipolar disorder are scarce, although cognition is thought to be a key determinant of functioning. The causal structure between cognition and psychosocial functioning in bipolar disorder is unknown. AIMS: We sought to examine the direction of causality between cognitive performance and functional outcome over 2 years in a large cohort of euthymic patients with bipolar disorder. METHOD: The sample consisted of 272 adults diagnosed with bipolar disorder who were euthymic at baseline, 12 and 24 months. All participants were recruited via the FondaMental Advanced Centers of Expertise in Bipolar Disorders. We used a battery of tests, assessing six domains of cognition at baseline and 24 months. Residual depressive symptoms and psychosocial functioning were measured at baseline and 12 and 24 months. The possible causal structure between cognition and psychosocial functioning was investigated with cross-lagged panel models with residual depressive symptoms as a covariate. RESULTS: The analyses support a causal model in which cognition moderately predicts and is causally primary to functional outcome 1 year later, whereas psychosocial functioning does not predict later cognitive performance. Subthreshold depressive symptoms concurrently affected functioning at each time of measure. CONCLUSIONS: Our results are compatible with an upward causal effect of cognition on functional outcome in euthymic patients with bipolar disorder. Neuropsychological assessment may help specify individual prognoses. Further studies are warranted to confirm this causal link and evaluate cognitive remediation, before or simultaneously with functional remediation, as an intervention to improve functional outcome.

Neural effects of antidepressant medication and psychological treatments: a quantitative synthesis across three meta-analyses.

BACKGROUND: Influential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes. AIMS: To test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network. METHOD: We employed a quantitative synthesis of three meta-analyses (n = 4206). First, we assessed the common and distinct neural changes evoked by antidepressant medication and psychotherapy, by contrasting two comparable meta-analyses reporting the neural effects of these treatments. Both meta-analyses included patients with affective disorders, including major depressive disorder, generalised anxiety disorder and panic disorder. The majority were assessed using negative-valence tasks during neuroimaging. Next, we assessed whether the neural changes evoked by antidepressants and psychotherapy overlapped with the brain's affect network, using data from a third meta-analysis of affect-based neural activation. RESULTS: Neural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network. CONCLUSIONS: This supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action.

Lowering dementia risk and slowing progression of disease: the role of cognitive reserve and cognitive training.

Almeida-Meza et al found an inverse correlation between cognitive reserve (associated with educational level, complexity of occupations and leisure activities) and dementia incidence. We suggest clarifying studies using their data-set and consider what can be done to modify socioeconomic inequalities that affect cognitive reserve or to slow early dementia.

Single-session Comprehend, Cope, and Connect intervention in acute and crisis psychology: A feasibility and acceptability study.

Comprehend, Cope, and Connect (CCC) is a third-wave cognitive behavioural approach developed for acute mental health services. The aim of this study was to assess feasibility and acceptability of a newly developed, manualized single-session CCC intervention delivered face-to-face with service users in acute and crisis psychology services in South London. The study adopted a within-subjects pre-post-test design. Participants (N = 23) were recruited from five acute psychiatric wards and a crisis resolution home treatment team. Service users had a range of diagnoses of complex and severe mental health conditions, in particular mood, personality, and psychotic disorders. Feasibility data were gathered for number of times the CCC formulation was accepted, duration of CCC intervention, clinician adherence to manualised protocol, and frequency of goal-based activity completion. Acceptability data on pre- and post-CCC mood and post-CCC helpfulness were self-reported by participants. Findings indicated a significant increase in positive mood (large effect) and moderate-high helpfulness rating postintervention. Most participants reported goal-based activity completion. There was high fidelity to the protocol, high percentage of acceptance of the formulation and formulation components completed, and frequent single-session completion. Single-session CCC appears feasible and acceptable in acute and crisis psychology services and yields formulation-driven goal-based activities intended to stabilize mental health crisis. High fidelity to formulation protocol suggests broader applications for single-session CCC, for example, to support clinical staff to manage crisis situations in their work environment or to train nonpsychologist clinicians to deliver the intervention for service users. A randomized controlled trial of single-session CCC would increase validity and generalisability of findings.

The effects of once- versus twice-weekly sessions on psychotherapy outcomes in depressed patients.

BACKGROUND: It is unclear what session frequency is most effective in cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression. AIMS: Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression. METHOD: We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients to once or twice weekly sessions of CBT or IPT over 16-24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted. RESULTS: Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates (n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00-2.18). CONCLUSIONS: In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes.

Effectiveness of cognitive-behavioural therapy for depression in advanced cancer: CanTalk randomised controlled trial.

BACKGROUND: Depression is one of the most common mental disorders in people with advanced cancer. Although cognitive-behavioural therapy (CBT) has been shown to be effective for depression in people with cancer, it is unclear whether this is the case for people with advanced cancer and depression. AIMS: We sought to determine whether CBT is more clinically effective than treatment as usual (TAU) for treating depression in people with advanced cancer (trial registration number ISRCTN07622709). METHOD: A multi-centre, parallel-group single-blind randomised controlled trial comparing TAU with CBT (plus TAU). Participants (n = 230) with advanced cancer and depression were randomly allocated to (a) up to 12 sessions of individual CBT or (b) TAU. The primary outcome measure was the Beck Depression Inventory-II (BDI-II). Secondary outcome measures included the Patient Health Questionnaire-9, the Eastern Cooperative Oncology Group Performance Status, and Satisfaction with Care. RESULTS: Multilevel modelling, including complier-average intention-to-treat analysis, found no benefit of CBT. CBT delivery was proficient, but there was no treatment effect (-0.84, 95% CI -2.76 to 1.08) or effects for secondary measures. Exploratory subgroup analysis suggested an effect of CBT on the BDI-II in those widowed, divorced or separated (-7.21, 95% CI -11.15 to -3.28). CONCLUSIONS: UK National Institute for Health and Care Excellence (NICE) guidelines recommend CBT for treating depression. Delivery of CBT through the Improving Access to Psychological Therapies (IAPT) programme has been advocated for long-term conditions such as cancer. Although it is feasible to deliver CBT through IAPT proficiently to people with advanced cancer, this is not clinically effective. CBT for people widowed, divorced or separated needs further exploration. Alternate models of CBT delivery may yield different results.

ICD-11 complex post-traumatic stress disorder: simplifying diagnosis in trauma populations.

ICD-11 complex post-traumatic stress disorder (PTSD) is a new disorder that describes the more complex reactions that are typical of individuals exposed to chronic trauma. The addition of this disorder as distinct from PTSD is expected to provide greater precision in the diagnosis of trauma populations and more personalised and effective treatment.

Integration of hypnotherapy with brief cognitive behaviour therapy (CBT) for treatment of depression.

The current study was planned to assess how the integration of brief cognitive behaviour therapy (CBT) with hypnotherapy can be productive for a client's quick progress in treatment. It illustrates the effectiveness of two methods of treatment integrated to make better prognosis in the treatment of a depressed Pakistani housewife aged 25 years, who had been suffering for a year. The sessions included hypnotic induction, teaching self-hypnosis with positive suggestions, mood monitoring, use of imagery and relaxation techniques along with specific strategies of brief CBT. Predominant feature of her clinical presentation was the belief of being unloved, and the negative thoughts of being devalued by the husband. Hypnotherapy contributed to achieving remarkable therapeutic progress in a relatively short time. At initial presentation, the depressive symptoms were extremely high as demonstrated by psychological assessment tests and Beck Depression Inventory (BDI). Subsequent test results indicated that she had returned to normal level of functioning (81-90) as assessed through the Global Assessment of Functioning Scale (GAFS). At the time of reporting the case, she was in the follow-up phase. The case highlights the value of hypnosis as a tool of empowerment especially important to diminish depression when used as an adjunct with cognitive behaviour therapy.

Ensuring research integrity: setting standards for robust and ethical conduct and reporting of research.

We present an account of why we decided to retract a paper. We discovered a lack of adherence to conventional trials registration, execution, interpretation and reporting, and consequently, with the authors, needed to correct the scientific record. We set out our responses in general to strengthen research integrity.Declaration of interestK.S.B. is Editor-in-Chief of the British Journal of Psychiatry. W.L., K.R.K. and S.M.L. are members of the senior editorial committee and the research integrity committee for the journal. In the past three years, S.M.L. has received research support from Janssen and Lundbeck, and personal support from Janssen, Otsuka and Sunovion.

A systematic scoping review of psychological therapies for psychosis within acute psychiatric in-patient settings.

BACKGROUND: People with psychotic disorders account for most acute admissions to psychiatric wards. Psychological therapies are a treatment adjunct to standard medication and nursing care, but the evidence base for such therapies within in-patient settings is unclear.AimsTo conduct a systematic scoping review of the current evidence base for psychological therapies for psychosis delivered within acute in-patient settings (PROSPERO: CRD42015025623). METHOD: All study designs, and therapy models, were eligible for inclusion in the review. We searched PubMed, PsycINFO, EThOS, ProQuest, conference abstracts and trial registries. RESULTS: We found 65 studies that met criteria for inclusion in the review, 21 of which were randomised controlled trials (RCTs). The majority of studies evaluated cognitive-behavioural interventions. Quality was variable across all study types. The RCTs were mostly small (n<25 in the treatment arm), and many had methodological limitations including poorly described randomisation methods, inadequate allocation concealment and non-masked outcome assessments. We found studies used a wide range of different outcome measures, and relatively few studies reported affective symptoms or recovery-based outcomes. Many studies described adaptations to treatment delivery within in-patient settings, including increased frequency of sessions, briefer interventions and use of single-session formats. CONCLUSIONS: Based on these findings, there is a clear need to improve methodological rigour within in-patient research. Interpretation of the current evidence base is challenging given the wide range of different therapies, outcome measures and models of delivery described in the literature.Declaration of interestNone.

Prolonged exposure therapy and supportive counselling for post-traumatic stress disorder in adolescents: task-shifting randomised controlled trial.

BACKGROUND: Empirical evidence on the effectiveness of evidence-based treatments for adolescents with post-traumatic stress disorder (PTSD) in low-resource settings is needed.AimsTo evaluate the comparative effectiveness of prolonged exposure and supportive counselling in adolescents with PTSD. METHOD: Sixty-three adolescents (13-18 years) with PTSD were randomly assigned to receive either of the interventions comprising 7-14 sessions of treatment (trial registration in the Pan African Clinical Trials Registry: PACTR201511001345372). The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale at pre-treatment, post-treatment, and at 3- and 6-month follow-up. RESULTS: Participants receiving prolonged exposure experienced greater improvement on the PTSD symptom severity scale than those receiving supportive counselling (between group differences at post-intervention, mean 12.49, 95% CI 6.82-18.17, P<0.001; d = 1.22). A similar effect size was maintained at 3-month (d = 0.85) and 6-month (d = 1.02) follow-up assessments. CONCLUSIONS: Adolescents with PTSD experienced greater benefit from prolonged exposure treatment when provided by non-specialist health workers (nurses) in a community setting.Declaration of interestNone.

Group cognitive behavioural treatment for insomnia in primary care: a randomized controlled trial.

BACKGROUND: Insomnia disorder is common and often co-morbid with mental health conditions. Cognitive behavioural therapy (CBT) for insomnia is effective, but is rarely implemented as a discrete treatment. The aim of this study was to evaluate the effectiveness of brief CBT groups for insomnia compared to treatment as usual (TAU) for insomnia delivered by mental health practitioners in a primary-care mental health service. METHOD: A total of 239 participants were randomized to either a five-session CBT group or to TAU. Assessments of sleep and of symptoms of depression and anxiety were carried out at baseline, post-treatment and at 20 weeks. Primary outcome was sleep efficiency post-treatment. RESULTS: Group CBT participants had better sleep outcomes post-treatment than those receiving TAU [sleep efficiency standardized mean difference 0.63, 95% confidence interval (CI) 0.34-0.92]. The effect at 20 weeks was smaller with a wide confidence interval (0.27, 95% CI -0.03 to 0.56). There were no important differences between groups at either follow-up period in symptoms of anxiety or depression. CONCLUSIONS: Dedicated CBT group treatment for insomnia improves sleep more than treating sleep as an adjunct to other mental health treatment.

Development of a family-based treatment for co-occurring intimate partner violence and child maltreatment: the MST-IPV model.

Intimate partner violence (IPV) is a significant global problem that affects the health of children, parents/caregivers and extended family. The effects can be lifelong and span generations. Treatments for IPV are focused largely on individual work with men as the primary aggressor. Even when the situation includes child maltreatment, generally all family members are referred to a host of providers for varied treatments. Traditionally, couples and family work does not occur. In this article, we detail the development and practice of a comprehensive treatment model for complex cases of co-occurring IPV and child maltreatment that is inclusive of the family and couple. Of particular note, the development of this model, Multisystemic Therapy for Intimate Partner Violence (MST-IPV), involved input from the IPV stakeholder community.

Exploratory RCT of a group psychological intervention for postnatal depression in British mothers of South Asian origin - ROSHNI-D.

BACKGROUND: Postnatal depression (PND) is a global public health problem. There is a high prevalence of PND amongst ethnic minority women and major ethnic inequalities in mental health care in the U.K. Language and cultural barriers pose a significant challenge for access to timely treatment and interventions for British South Asian (BSA) women with PND. METHODS: The study, carried out in Manchester and Lancashire, England, was a two-arm single-blind exploratory randomised controlled trial. BSA women (N = 83) having a baby <12 months were randomised either to the group receiving the culturally adapted Positive Health Programme (PHP) (n = 42) or to the group receiving treatment as usual (TAU) (n = 41). Follow-up assessments were at 3 months (end of intervention) and 6 months after randomisation. RESULTS: Using an intention to treat analysis, there was no significant difference between PHP intervention and TAU groups in depression measured using Hamilton Depression Rating Scale both at 3 and 6 months follow up. Using modified intention to treat analysis, women who attended four or more sessions showed significant reduction in depression in the PHP group compared to the TAU group and the greater number of sessions attended was associated with greater reductions in depression scores. LIMITATIONS: The sample was relatively small and the study was conducted in one geographical area in Northwest England; hence, these results may not be generalizable to other regions and populations. CONCLUSION: The recruitment and trial retention figures highlighted the ability of the research team to engage with BSA women, having implications in planning services for this group. TRIAL REGISTRATION: Clinicaltrials.govNCT01838889.

A service evaluation of phased- and stepped-care psychological support for health and social care workers during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has disproportionally affected the mental health of health and social care workers (HSCWs), with many experiencing symptoms of depression, anxiety and post-traumatic stress disorder. Psychological interventions have been offered via mental health services and in-house psychology teams, but their effectiveness in this context is not well documented. AIMS: To evaluate a stepped-care psychological support pathway for HSCWs from Homerton Healthcare Foundation Trust in London, which offered psychological first aid, evidence-based psychological therapies and group-based well-being workshops. METHOD: The service evaluation used a pre-post approach to assess depression, anxiety, functional impairment and post-traumatic stress disorder symptom change for those who attended sessions of psychological first aid, low- or high-intensity cognitive-behavioural therapy or a combination of these. In addition, the acceptability of the psychological first aid sessions and well-being workshops was explored via feedback data. RESULTS: Across all interventions, statistically significant reductions of depression (d = 1.33), anxiety (d = 1.37) and functional impairment (d = 0.93) were observed, and these reductions were equivalent between the interventions, as well as the demographic and occupational differences between the HSCWs (ethnicity, staff group and redeployment status). HSCWs were highly satisfied with the psychological first aid and well-being workshops. CONCLUSIONS: The evaluation supports the utility of evidence-based interventions delivered as part of a stepped-care pathway for HSCWs with common mental health problems in the context of the COVID-19 pandemic. Given the novel integration of psychological first aid within the stepped-care model as a step one intervention, replication and further testing in larger-scale studies is warranted.

Personalised psychotherapy in primary care: evaluation of data-driven treatment allocation to cognitive-behavioural therapy versus counselling for depression.

BACKGROUND: Various effective psychotherapies exist for the treatment of depression; however, only approximately half of patients recover after treatment. In efforts to improve clinical outcomes, research has focused on personalised psychotherapy - an attempt to match patients to treatments they are most likely to respond to. AIM: The present research aimed to evaluate the benefit of a data-driven model to support clinical decision-making in differential treatment allocation to cognitive-behavioural therapy versus counselling for depression. METHOD: The present analysis used electronic healthcare records from primary care psychological therapy services for patients receiving cognitive-behavioural therapy (n = 14 544) and counselling for depression (n = 4725). A linear regression with baseline sociodemographic and clinical characteristics was used to differentially predict post-treatment Patient Health Questionnaire (PHQ-9) scores between the two treatments. The benefit of differential prescription was evaluated in a held-out validation sample. RESULTS: On average, patients who received their model-indicated optimal treatment saw a greater improvement (by 1.78 PHQ-9 points). This translated into 4-10% more patients achieving clinically meaningful changes. However, for individual patients, the estimated differences in benefits of treatments were small and rarely met the threshold for minimal clinically important differences. CONCLUSION: Precision prescription of psychotherapy based on sociodemographic and clinical characteristics is unlikely to produce large benefits for individual patients. However, the benefits may be meaningful from an aggregate public health perspective when applied at scale.