Adjusting expected deaths for mortality displacement during the COVID-19 pandemic: a model based counterfactual approach at the level of individuals.

BACKGROUND: Near-real time surveillance of excess mortality has been an essential tool during the COVID-19 pandemic. It remains critical for monitoring mortality as the pandemic wanes, to detect fluctuations in the death rate associated both with the longer-term impact of the pandemic (e.g. infection, containment measures and reduced service provision by the health and other systems) and the responses that followed (e.g. curtailment of containment measures, vaccination and the response of health and other systems to backlogs). Following the relaxing of social distancing regimes and reduction in the availability of testing, across many countries, it becomes critical to measure the impact of COVID-19 infection. However, prolonged periods of mortality in excess of the expected across entire populations has raised doubts over the validity of using unadjusted historic estimates of mortality to calculate the expected numbers of deaths that form the baseline for computing numbers of excess deaths because many individuals died earlier than they would otherwise have done: i.e. their mortality was displaced earlier in time to occur during the pandemic rather than when historic rates predicted. This is also often termed "harvesting" in the literature. METHODS: We present a novel Cox-regression-based methodology using time-dependent covariates to estimate the profile of the increased risk of death across time in individuals who contracted COVID-19 among a population of hip fracture patients in England (N = 98,365). We use these hazards to simulate a distribution of survival times, in the presence of a COVID-19 positive test, and then calculate survival times based on hazard rates without a positive test and use the difference between the medians of these distributions to estimate the number of days a death has been displaced. This methodology is applied at the individual level, rather than the population level to provide a better understanding of the impact of a positive COVID-19 test on the mortality of groups with different vulnerabilities conferred by sociodemographic and health characteristics. Finally, we apply the mortality displacement estimates to adjust estimates of excess mortality using a "ball and urn" model. RESULTS: Among the exemplar population we present an end-to-end application of our methodology to estimate the extent of mortality displacement. A greater proportion of older, male and frailer individuals were subject to significant displacement while the magnitude of displacement was higher in younger females and in individuals with lower frailty: groups who, in the absence of COVID-19, should have had a substantial life expectancy. CONCLUSION: Our results indicate that calculating the expected number of deaths following the first wave of the pandemic in England based solely on historical trends results in an overestimate, and excess mortality will therefore be underestimated. Our findings, using this exemplar dataset are conditional on having experienced a hip fracture, which is not generalisable to the general population. Fractures that impede mobility in the weeks that follow the accident/surgery considerably shorten life expectancy and are in themselves markers of significant frailty. It is therefore important to apply these novel methods to the general population, among whom we anticipate strong patterns in mortality displacement - both in its length and prevalence - by age, sex, frailty and types of comorbidities. This counterfactual method may also be used to investigate a wider range of disruptive population health events. This has important implications for public health monitoring and the interpretation of public health data in England and globally.

Prevalence of moderate or greater permanent childhood hearing impairment and effectiveness of targeted surveillance for babies who pass newborn hearing screening.

OBJECTIVE: To assess the utility of targeted surveillance for the identification of moderate to profound PCHI in babies who pass newborn hearing screening in England and have risk factors. DESIGN: Retrospective analysis. STUDY SAMPLE: A total of 3,957,891 children born 01/04/2012-31/03/2018 in England. RESULTS: A total of 7148 PCHI cases were identified (1.81 per 1,000 babies). 6,707 followed an immediate referral from the screen (1 per 16 referrals), 51 followed targeted surveillance referral (1 per 540 referrals) and 390 without a referral. Audiology uptake was higher following an immediate referral (96.7% overall, 77.2% within NHSP-defined timescales) than following targeted surveillance (63.8% overall, 51.1% within 52 weeks of birth). The screening was 94.5% sensitive overall, with similar sensitivities for each of the risk factors. General linearised logistic regression models identified syndrome as the risk factor with the highest odds ratio (14.08 for all babies, 22.19 for babies without immediate referral). Close family history of hearing loss was the next highest (10.93 for all babies, 12.29 for babies without immediate referral). CONCLUSION: The evidence for a targeted surveillance programme, based on risk factors, for babies in England who pass the newborn screen is not strong.

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.

Trajectories of depression and generalised anxiety symptoms over the course of cognitive behaviour therapy in primary care: an observational, retrospective cohort.

BACKGROUND: Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment for depression and anxiety. However, most research has focused on the sum scores of symptoms. Relatively little is known about how individual symptoms respond. METHODS: Longitudinal models were used to explore how depression and generalised anxiety symptoms behave over the course of CBT in a retrospective, observational cohort of patients from primary care settings (n = 5306). Logistic mixed models were used to examine the probability of being symptom-free across CBT appointments, using the 9-item Patient Health Questionnaire and the 7-item Generalised Anxiety Disorder scale as measures. RESULTS: All symptoms improve across CBT treatment. The results suggest that low mood/hopelessness and guilt/worthlessness improved quickest relative to other depressive symptoms, with sleeping problems, appetite changes, and psychomotor retardation/agitation improving relatively slower. Uncontrollable worry and too much worry were the anxiety symptoms that improved fastest; irritability and restlessness improved the slowest. CONCLUSIONS: This research suggests there is a benefit to examining symptoms rather than sum scores alone. Investigations of symptoms provide the potential for precision psychiatry and may explain some of the heterogeneity observed in clinical outcomes when only sum scores are considered.

The early impact of COVID-19 on primary care psychological therapy services: A descriptive time series of electronic healthcare records.

BACKGROUND: There are growing concerns about the impact of the COVID-19 pandemic on mental health. With government-imposed restrictions as well as a general burden on healthcare systems, the pandemic has the potential to disrupt the access to, and delivery of, mental healthcare. METHODS: Electronic healthcare records from primary care psychological therapy services (Improving Access to Psychological Therapy) in England were used to examine changes in access to mental health services and service delivery during early stages of the COVID-19 pandemic. A descriptive time series was conducted using data from five NHS trusts to examine patterns in referrals to services (1st January 2019 to 24th May 2020) and appointments (1st January 2020 to 24th May 2020) taking place. FINDINGS: The number of patients accessing mental health services dropped by an average of 55% in the early weeks after the March 2020 lockdown was announced, reaching a maximum reduction of 74% in the initial 3 weeks after lockdown in the UK, which gradually recovered to a 28% reduction by May. We found some evidence suggesting changes in the sociodemographic and clinical characteristics of referrals. Despite a reduction in access, the impact on appointments appeared limited with service providers shifting to remote delivery of care. INTERPRETATION: Services appeared to adapt to provide continuity of care in mental healthcare. However, patients accessing services reduced, potentially placing a future burden on service. Despite the observational nature of the data, the present study can inform the planning of service provision and policy. FUNDING: AD and TS were funded by Innovate UK (KTP #11,105).

Effective dose 50 method as the minimal clinically important difference: Evidence from depression trials.

OBJECTIVE: Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity. STUDY DESIGN AND SETTINGS: The present analysis used secondary data from 2 randomized controlled trials for depression (n = 1,122) to calibrate the Global Rating of Change with the PHQ-9 and GAD-7. The MCID was defined as a change in scores corresponding to a 50% probability of patients "feeling better", given their baseline severity, referred to as Effective Dose 50 (ED50). RESULTS: MCID estimates depended on baseline severity and ranged from no change for very mild up to 14 points (52%) on the PHQ-9 and up to 10 points (48%) on the GAD-7 for very high severity. The average MCID estimates were 3.7 points (23%) and 3.3 (28%) for the PHQ-9 and GAD-7 respectively. CONCLUSION: The ED50 method generates MCID estimates across the spectrum of baseline severity, offering greater precision but at the cost of greater complexity relative to population average estimates. This has important implications for evaluations of treatments and clinical practice where users can use these results to tailor the MCID to specific populations according to baseline severities.

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta-analysis.

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta-analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty-two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post-traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross-sectional research. Our findings suggest that there may be distinct psy-chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.

Prevalence and risk factors for HIV, hepatitis B, and hepatitis C in people with severe mental illness: a total population study of Sweden.

BACKGROUND: Severe mental illness is associated with increased morbidity and mortality. The elevated risk of blood-borne viruses (BBVs) in people with severe mental illness is of concern, but the full extent of this problem is unclear. We aimed to determine the prevalence of and risk factors for BBVs in people with severe mental illness. METHODS: In this nationwide, population-based, cross-sectional study, we estimated the point prevalence of HIV, hepatitis B (HBV), and hepatitis C (HCV) in people with severe mental illness, including the total adult (≥18 years) Swedish population. We defined severe mental illness as a clinical diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic illness according to the Swedish version of the International Statistical Classification of Diseases version 8, 9, or 10. We used multivariable logistic regression to determine the odds of BBVs in individuals with severe mental illness, relative to the general population, and to identify independent risk factors (age, sex, immigration status, socioeconomic status, education, and substance misuse) for BBV infection. We also did a sensitivity analysis excluding BBV diagnoses made before the introduction of the Register for Infection Disease Control (1997). FINDINGS: Of 6 815 931 adults in Sweden, 97 797 (1·43%) individuals had a diagnosis of severe mental illness. Prevalence of BBVs was elevated in people with severe mental illness, of which 230 (0·24%) had HIV, 518 (0·53%) had HBV, and 4476 (4·58%) had HCV. After accounting for sociodemographic characteristics, the odds of HIV were 2·57 (95% CI 2·25-2·94, p<0·0001) times higher in people with severe mental illness than in the general population, whereas the odds of HBV were 2·29 (2·09-2·51, p<0·0001) times higher and the odds of HCV were 6·18 (5·98-6·39, p<0·0001) times higher. Substance misuse contributed most to the increased risk of BBV: after adjustment, odds ratios were 1·61 (1·40-1·85, p<0·0001) for HIV, 1·28 (1·16-1·41, p<0·0001) for HBV, and 1·72 (1·67-1·78, p<0·0001) for HCV. INTERPRETATION: Our results highlight the need to address the issue of higher prevalence of BBVs in people with severe mental illness and identify interventions preventing infection. Targeting of comorbid substance misuse would have particular effect on reduction of BBV prevalence in this population. FUNDING: Medical Research Council and Swedish Research Council.