We draw from the Health Technology Assessment (HTA) literature to propose how hospitals and local health networks can prepare the key components of early economic evaluations to support the development and management of health service interventions.

Using the case example of a proposed intervention for older people in the Emergency Department (ED), a conceptual logic model of a new health service intervention is articulated to inform the structuring and population of a decision-analytic model using observed data on the existing care comparator and structured elicitation exercise of initial stakeholder expectations of intervention effects.

The elicited patient pathway probabilities and lengths of stay quantities profile which of the existing types of patients are expected to avoid the ED and how this impacts the lengths of stay across the system. The exercise also quantifies the stakeholders’ uncertainty and disagreement, with qualitative insights into why. The elicitation exercise participants draw upon the rationale for how the intervention is expected to affect a change within the local context, as captured within the logic model, together with the descriptive analyses of the characteristics and utilization of their target population. Feedback indicates the methods are acceptably robust yet pragmatic enough for healthcare delivery settings.

As proposed in this paper, HTA methods can be used to capture how key stakeholders initially expect a service intervention to affect a change within their local context. The example results can be used in a decision-analytic model to guide the development and management of an intervention.

People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally.

We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation.

Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups

The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Fluoride exposure has been associated with thyroid dysfunction, but fluoride's impact on thyroid function in pregnancy is unclear, especially during early gestation when the fetus is dependent on maternal thyroid hormone. We examined the potential thyroid-disrupting effects of maternal fluoride exposure in pregnancy and tested whether thyroid disruption in pregnancy mediates the association between maternal fluoride exposure and child intelligence quotient (IQ) among Canadian mother-child dyads living in areas with optimal fluoridation.

We measured fluoride concentrations in drinking water and in spot urine samples collected in each trimester from pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals study. We also measured thyroid hormone (thyroid stimulating hormone [TSH], free thyroxine [FT4], and total thyroxine [TT4]) levels during the first trimester of pregnancy and categorized women as euthyroid (n=1301), subclinical hypothyroid (n=100), or primary hypothyroid (n=28). Those categorized as primary hypothyroid were combined with an additional 79 women who reported clinical diagnoses at time of study enrolment (total n=107). In a sample of 1508 women, we used logistic regression to estimate the association between fluoride exposure and risk of either subclinical or primary hypothyroidism, separately, and linear regression to estimate associations between fluoride exposure and women's thyroid hormone levels (TSH, FT4, TT4). We tested effect modification by child sex and thyroid peroxidase (TPO) antibody status. In a subsample of 439 mother-child pairs, we measured child Full-Scale IQ (FSIQ) at 3-4 years of age using the Wechsler Preschool and Primary Scale of Intelligence. We used linear regression to test associations between maternal hypothyroidism or thyroid hormone levels, and children's FSIQ scores. Finally, mediation analysis in the counterfactual framework was used to estimate the proportion of the effect of maternal fluoride exposure on child FSIQ mediated by maternal hypothyroidism, through evaluation of the natural direct (not through hypothyroidism) and indirect (through hypothyroidism) effects.

Using categorical measures of thyroid status, a 0.5 mg/L increase in water fluoride concentration was associated with a 1.64 (95% confidence interval [CI], 1.04 to 2.58) increased odds of primary hypothyroidism. This association was stronger among women with normal TPO antibody levels (< 5.61 IU/mL) (odds ratio, 2.80; 95% CI, 1.24 to 6.36). In contrast, we did not find a significant association between maternal urinary fluoride and hypothyroidism. For continuous measures of thyroid hormone levels, a 1 mg/L increase in maternal urinary fluoride was associated with a 35% (p=0.01) increase in TSH among women pregnant with a female fetus. In our subsample analyses, children born to women with primary hypothyroidism had lower FSIQ than children of euthyroid women, especially among boys (B, 8.78; 95% CI, -16.78 to -0.79). In contrast, maternal TSH, FT4, and TT4 levels were not significantly associated with child FSIQ scores. Maternal primary hypothyroidism did not significantly mediate the relationship between maternal water fluoride concentration and child FSIQ (p natural indirect effect= .35).

Fluoride in drinking water may increase the risk of hypothyroidism in pregnancy. Thyroid dysfunction in pregnancy may be one mechanism underlying developmental neurotoxicity of fluoride.

Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.

This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.

We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.

We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.

A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.

How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.

Evidence supporting collection of follow-up blood cultures for Gram-negative bacteremia is mixed. We sought to understand why providers order follow-up blood cultures when managing P. aeruginosa bacteremia and whether follow-up blood cultures in this context are associated with short- and long-term survival.

We conducted a retrospective cohort study of adult inpatients with P. aeruginosa bacteremia at the University of Maryland Medical Center in 2015–2020. Kaplan-Meier survival curves and Cox regression with time-varying covariates were used to evaluate the association between follow-up blood cultures and time to mortality within 30 days of first positive blood culture. Provider justifications for follow-up blood cultures were identified through chart review.

Of 159 eligible patients, 127 (80%) had follow-up blood cultures, including 9 (7%) that were positive for P. aeruginosa and 10 (8%) that were positive for other organisms. Follow-up blood cultures were typically collected “to ensure clearance” or “to guide antibiotic therapy.” Overall, 30-day mortality was 25.2%. After risk adjustment for patient characteristics, follow-up blood cultures were associated with a nonsignificant reduction in mortality risk (hazard ratio, 0.43; 95% confidence interval, 1.08; P = .071). In exploratory analyses, the potential mortality reduction from follow-up blood cultures was driven by their use in patients with Pitt bacteremia scores >0.

Follow-up blood cultures are commonly collected for P. aeruginosa bacteremia but infrequently identify persistent bacteremia. Targeted use of follow-up blood cultures based on severity of illness may reduce unnecessary culturing.

Lithium was first found to have an acute antimanic effect in 1948 with further corroboration in the early 1950s. It took some time for lithium to become the standard treatment for relapse prevention in bipolar affective disorder. In this study, our aims were to examine the factors associated wtih the likelihood of maintaining lithium levels within the recommended therapeutic range and to look at the stability of lithium levels between blood tests. We examined this relation using clinical laboratory serum lithium test requesting data collected from three large UK centres, where the approach to managing patients with bipolar disorder and ordering lithium testing varied.

46,555 lithium rest requests in 3,371 individuals over 7 years were included from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where, on subsequent testing, lithium results remained in the same category or switched category. We then examined the association between testing interval and proportion remaining within target, and the effect of age, duration of lithium therapy and testing history.

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall 3-monthly testing was associated with 90% of lithium results remaining within range compared with 85% at 6-monthly intervals. At all test intervals, lithium test result history in the previous 12-months was associated with the proportion of next test results on target (BNF/NICE criteria), with 90% remaining within range target after 6-months if all tests in the previous 12-months were on target. Age/duration of lithium therapy had no significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) than those in the 0.40–0.79 mmolL group (2%), irrespective of testing frequency. Thus prior history in relation to stability of lithium level in the previous 12 months is a predictor of future stability of lithium level.

We propose that, for those who achieve 12-months of lithium tests within the 0.40–0.79mmol/L range, it would be reasonable to increase the interval between tests to 6 months, irrespective of age, freeing up resource to focus on those less concordant with their lithium monitoring. Where lithium level is 0.80–0.99mmol/L test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

The aim of this study is to systematically investigate the demographic and disease predictors of cognitive and behavioural phenotype in the largest cohort of children with NF1 published to date. Based on previously published research, we examine the potential role of demographic predictors such as age, sex, SES, parental NF1 status as well as the neurological complications such as epilepsy and brain tumours in NF1 associated cognitive/ behavioural impairments.

In this cross-sectional study design, participant data were drawn from two large databases which included (i) A clinical database of all patients with NF1 seen in a clinical psychological service from 2010 to 2019 and (ii) A research dataset from two previously published studies (2,8). The complex National NF1 service based within Manchester regional genetic services is set up for individuals with complex NF1 (https://www.mangen.co.uk/healthcare-professionals/clinical-genomic-services/nf1/) in the North of the UK. Children were referred to the psychological services by NF1 clinicians if psychological assessment was warranted based on parental reports. In order to reduce clinic referral bias, the clinical sample was supplemented by including participants that were seen solely for the purposes of research studies within our centre.

Relative to population norms, 90% of the NF1 sample demonstrated significantly lower scores in at least one cognitive or behavioral domain. Family history of NF1 and lower SES were independently associated with poorer cognitive, behavioral and academic outcomes. Neurological problems such as epilepsy and hydrocephalus were associated with lower IQ and academic skills.

Cognitive and behavioural phenotypes commonly emerge via a complex interplay between genes and environmental factors, and this is true also of a monogenic condition such as NF1. Early interventions and remedial education may be targeted to risk groups such those with familial NF1, families with lower SES and those with associated neurological comorbidities.

This study examined lithium results and requesting patterns over a 6-year period, and compared these to guidance.

Bipolar disorder is the 4th most common mental health condition, affecting ~1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is recommended by NICE as a first-line treatment.

We have previously shown in other areas that laboratory testing patterns are highly variable with sub-optimal conformity to guidance.

Lithium requests received by Clinical Biochemistry Departments at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012–2018 were extracted from Laboratory Information and Management Systems (46,555 requests; 3,371 individuals). We categorised by request source, lithium concentration and re-test intervals.

Many lithium results were outside the NICE therapeutic window (0.6–0.99mmol/L); 49.3% were below the window and 6.1% were above the window (median [Li]:0.61mmol/L). A small percentage were found at the extremes (3.2% at <0.1mmol/L, 1.0% at >1.4mmol/L). Findings were comparable across all sites.

For requesting interval, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak evident at 6 months, as recommended for those <65 years old on unchanging therapy. There was a peak at 0–7 days, reflecting those requiring closer monitoring (e.g. treatment initiation or results suggesting toxicity).

However, 77.6% of tests were requested outside expected testing frequencies.

We showed: (a) lithium levels are often maintained at the lower end of the NICE recommended therapeutic range (and the BNF range: 0.4-1.0mmol/L); (b) patterns of lithium results and testing frequency are comparable across three sites with differing models of care; (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly interval, but not at 6-monthly intervals; (d) Many tests were repeated outside these expected frequencies (contrary to NICE guidance).

Little is known about the determinants of community integration (i.e. recovery) for individuals with a history of homelessness, yet such information is essential to develop targeted interventions.

We recruited homeless Veterans with a history of psychotic disorders and evaluated four domains of correlates of community integration: perception, non-social cognition, social cognition, and motivation. Baseline assessments occurred after participants were engaged in supported housing services but before they received housing, and again after 12 months. Ninety-five homeless Veterans with a history of psychosis were assessed at baseline and 53 returned after 12 months. We examined both cross-sectional and longitudinal relationships with 12-month community integration.

The strongest longitudinal association was between a baseline motivational measure and social integration at 12 months. We also observed cross-sectional associations at baseline between motivational measures and community integration, including social, work, and independent living. Cross-lagged panel analyses did not suggest causal associations for the motivational measures. Correlations with perception and non-social cognition were weak. One social cognition measure showed a significant longitudinal correlation with independent living at 12 months that was significant for cross-lagged analysis, consistent with a causal relationship and potential treatment target.

The relatively selective associations for motivational measures differ from what is typically seen in psychosis, in which all domains are associated with community integration. These findings are presented along with a partner paper (Study 2) to compare findings from this study to an independent sample without a history of psychotic disorders to evaluate the consistency in findings regarding community integration across projects.