Umeå University's logo

BACKGROUND: Harmonizing core outcome domains allows for pooling data, comparing interventions, and streamlining research evaluation. At the same time clinicians require concise and feasible measures for routine practice. Considering the heterogeneity of post-COVID-19 condition, a biopsychosocial approach requires sufficient coverage of the psychosocial dimension with assessments. Previous recommendations for core outcome sets have serious limitations regarding the psychosocial aspects of post-COVID-19 condition. This paper specifically focuses on psychosocial outcomes for adults with post-COVID-19 condition, providing both a comprehensive set of outcome domains for research and a streamlined clinical core set tailored for routine clinical use.

METHODS: In a structured Consensus Development Approach, the European Network to improve diagnostic, treatment, and healthcare for patients with persistent somatic symptoms (EURONET-SOMA) developed psychosocial core outcome domains and assessments regarding post-COVID-19 condition. The experts identified variables and instruments which should be considered in studies on adults suffering from post-COVID-19 condition, and which are feasible in the clinical setting and relevant for research.

RESULTS: We identified three higher-order dimensions with each encompassing several domains: The first higher-order dimension, "outcomes", encompasses (1) the classification/ diagnostics of post-COVID-19 condition, (2) somatic symptoms (including fatigue), (3) the psychopathological status and mental comorbidities, (4) the physical status and somatic comorbidities, (5) neurocognitive symptoms, and (6) illness consequences. The second higher-order domain "mechanisms" encompasses (7) cognitive components, (8) affective components, (9) behavioral components, (10) social components, and (11) psychobiological bridge markers (e.g., neuroimmunological and psychoneuroendocrinological variables). The third higher-order domain, "risk factors", includes factors such as (12) socioeconomic status and sociocultural factors, (13) pre-existing mental and somatic health issues, (14) personality factors (e.g., neuroticism), (15) adverse childhood experiences, (16) ongoing disability or pension claim, and (17) social media use. For each domain, specific instruments are suggested for research purposes and clinical use.

CONCLUSIONS: The recommended core domains help to increase consistency in a biopsychosocial approach to post-COVID-19 condition across investigations, improve synergies, and facilitate decision-making when comparing different interventional approaches. It allows to better identify relevant subgroups in heterogeneous post-COVID-19 condition populations offering practical tools for routine clinical practice through the clinical core set.

Objectives: Fear of falling (FoF) is a common problem among older adults. It can lead to reduced quality of life and less physical activity, which increases fall risk. Earlier work has shown that FoF can be a manifestation of executive dysfunction in adults over 50 years, but studies on people over age 75 years are lacking. Executive functions (EFs) are cognitive functions associated with the frontal lobes and the prefrontal cortex. The aim of this study was to assess associations of EFs and FoF among people aged 80 years or older.

Methods: This cross-sectional study was based on data from the Northern Sweden Silver-MONICA study and included 434 participants aged 80 years or older. EFs were assessed with the Frontal Assessment Battery (FAB) and FoF with the Falls Self-Efficacy Scale–International (FES-I). Multivariable linear regression analysis was used to examine associations among EF, FoF, and a comprehensive set of adjustment factors. Pearson correlation analysis was used to evaluate associations of FES-I and the subitems of the FAB.

Results: EFs as measured by FAB were inversely associated with FoF (β = -0.23; 95% confidence interval, -0.42 to -0.03; p = 0.021), even after comprehensive adjustments. The FAB subitems measuring lexical fluency, inhibitory control, sustained attention, self-organization, motor programming, and planning also were inversely associated with FoF.

Conclusions: Lower EF is associated with higher FoF among people aged 80 years or older. This information is important for treating and preventing FoF in this population.

Background: By entering collecting duct principal cells via the epithelial sodium channel (ENaC), lithium is capable of inducing vasopressin insensitivity, resulting in excessive urine production, nephrogenic diabetes insipidus (NDI) and potential for other long-term forms of renal dysfunction. ENaC inhibitors (ENaC-I) such as amiloride have been shown in animal models to minimise this adverse effect, and while ENaC-I are often considered an effective strategy, the literature on ENaC-I for lithium-related polyuria has not yet been synthesised despite the importance of this topic. This review aimed to identify all published evidence for adjunctive use of an ENaC-I for lithium-related polyuria to estimate its effectiveness while also exploring potential moderators of effectiveness.

Method: The systematic search covered databases MEDLINE, EMBASE and PsycINFO complemented by handsearches, aiming to identify all studies of ENaC-I interventions in lithium-treated patients with pre- and post-ENaC-I polyuria as outcomes.

Results: 10 studies totalling 25 participants were eligible for inclusion and were synthesised narratively. Amiloride was the ENaC-I used in 24/25 participants, and triamterene in the other. 8/10 publications were single case reports, 4 of which presented substantial confounding issues. Clear improvements to polyuria were demonstrated in most papers, including the two larger studies.

Conclusions: Although it appears very likely that ENaC inhibitors help ameliorate polyuria in lithium-treated patients, the quantity and quality of evidence is low. Heterogeneity in patient characteristics, intervention characteristics and study designs limit conclusions regarding the contribution of factors likely to influence ENaC-I effectiveness for lithium-induced polyuria. Besides, adverse effects require further exploration.

Background: Long-term lithium treatment decreases kidney function. However, it remains unclear whether stopping lithium improves kidney function.

Objectives: To study kidney function in patients who stopped and subsequently restarted lithium treatment.

Methods: Mirror-image design using data from the LiSIE retrospective cohort study. The mirror was set to when lithium was stopped with a 5-year pre- and post-mirror period. Adult patients with bipolar, schizoaffective disorder or unipolar depression, who had lithium ≥4.5 years in the pre-mirror period, were included. Creatinine measurements were available from 1997 to 2017. The main outcome was the difference in mean annual change of the estimated glomerular filtration rate (eGFR) adjusted for sex, hypertension and diabetes mellitus.

Results: A total of 168 participants (94 women, 74 men) were included. Mean annual eGFR change was −1.58 (−1.87 to −1.28) mL/min/1.73 m²/year before and −0.023 (−0.49 to +0.44) mL/min/1.73 m²/year after lithium discontinuation (p < 0.0001 for difference). The improvement was 0.77 (0.35–1.20) mL/min/173 m²/year in participants with eGFR >60 mL/min/1.73 m², and 3.03 (2.15–3.92) mL/min/1.73 m²/year for participants with eGFR <30 mL/min/1.73 m². The effect was persistent over the 5-year post-mirror study period. For participants restarting lithium, the mean annual eGFR change was −1.71 (−2.26 to −1.16) mL/min/1.73 m²/year, a setback compared to their lithium-free post-mirror period (p < 0.0001). We did not see any difference compared to the pre-mirror period (p = 0.51).

Conclusions: Stopping lithium slowed down mean eGFR decline. This effect was more pronounced in participants with lower eGFR at the time of lithium discontinuation. In participants who restarted lithium, the annual decline of eGFR reverted to pre-lithium discontinuation levels.

Objectives: Previous research has suggested antiviral properties for lithium, including potential effectiveness against COVID-19 in vitro. This study aimed to investigate the impact of lithium and other psychotropic drugs on the risks of mortality, hospitalization, and ICU admission due to COVID-19 among individuals with bipolar disorder. The primary objective was to assess whether lithium was beneficial in COVID-19-infection in a real-world population.

Methods: Retrospective register study using data from multiple Swedish patient registers, including 39,063 individuals in Sweden with bipolar disorder and prescribed mood stabilizers. Outcomes included COVID-19-associated death, hospitalization, and ICU admission between 11 March 2020 and 10 March 2021. Multivariate logistic regression adjusted for age, sex, and somatic comorbidities was conducted.

Results: Lithium were prescribed to 44.2 % of patients, either as mono- or combination therapy; other mood stabilizers were prescribed to 55.8 %. There were no significant associations between lithium and COVID-19-associated death, hospitalization, or ICU admission. Atypical antipsychotics were associated with increased odds ratios for COVID-19-associated death (OR 1.58 [95 % CI 1.01–2.47]), hospitalization (OR 1.80 [95 % CI 1.49–2.18]), and ICU admission (OR 2.25 [95 % CI 1.33–3.80]). Benzodiazepines were associated with a significant increase in COVID-19-associated death (OR 1.54 [95 % CI 1.01–2.35]) and hospitalization OR 1.26 [95 % CI 1.03–1.53]). In an ad hoc analysis, lithium monotherapy was, however, associated with reduced hospitalizations and ICU admissions.

Conclusions: Our findings weaken the hypothesis that lithium reduces the risk of severe events associated with COVID-19 infection in bipolar disorder.

Background: Despite the therapeutic benefits, non-adherence to lithium is common. One recent study showed that most patients discontinue lithium due to adverse effects. Little is known about individuals starting and discontinuing lithium repeatedly.

Objectives: We aimed to determine reasons for discontinuing and restarting lithium multiple times in patients with bipolar or schizoaffective disorder.

Design: Retrospective cohort study based on psychiatric case records of the SLaM Biomedical Research Centre Case Register (SLaM BRC case register).

Method: Anonymised clinical data were extracted via the Clinical Record Interactive Search (CRIS) application. Patients with at least three events of lithium discontinuation between 2012 and 2022 were included.

Results: Of 2888 eligible patients, 123 patients had discontinued lithium on at least three occasions. Psychiatric reasons, such as suspected lack of insight, feeling subjectively well or disagreeing with diagnosis, were the most common reasons for lithium discontinuations. They accounted for 77.2% of cases in the first event of discontinuation, 73.2% in the second and 72.3% in the third event. Adverse physical effects accounted for 19.5% of cases in the first event of discontinuation, 25.2% in the second and 26.0% in the third event. Relapse into the underlying affective disorder accounted for 83.7% each of reinstatements in the first and second events and 82.1% in the third event.

Discussion: In our sample, lithium was discontinued due to adverse effects in only a minority of patients. In most cases, the reasons for lithium discontinuation were considered psychiatric. Lithium was mainly restarted due to relapse. This warrants a better understanding of the reasons for repeatedly discontinuing lithium and the best way to promote lithium adherence to prevent a perpetual cycle of remitting when on lithium and relapsing when off lithium.

The COVID-19 pandemic led to reports of increased levels of psychological distress and mental health problems world-wide. In Sweden, contrary to most other countries, the COVID-19 strategy was mainly based on voluntary restrictions. It remains unclear whether this reduced mental health problems. We therefore aimed to investigate the long-term impact of the COVID-19 pandemic on mental health in Sweden in terms of mental health service utilisation, antidepressant and anxiolytic/sedative use, and suicide rates for the two years before, during and after the pandemic in a nationwide retrospective register study, covering the entire Swedish population from ten years of age between 1 January 2018 and 31 December 2023. Publicly available data from three national registers were used. We found that, despite the stress induced by the COVID-19 pandemic, there was neither an overall impact on mental health service utilisation nor a post-pandemic rebound. Nonetheless, there were vulnerable subgroups, which could be overlooked when only examining the population as a whole. Young women and girls fared worse in terms of psychoactive substance use and anxiety. Older men fared worse in terms of suicide rates. Identifying vulnerable populations already now, may be a means to effectively mitigate mental health problems during future pandemics.

Background: At the beginning of the COVID-19 pandemic, concerns arose about a possible rise in alcohol consumption. Early surveys, however, more commonly pointed towards a decrease of alcohol use. But studies based on self-reports may underestimate alcohol use. They also depend on the population sampled. Because of border closures and gastronomy restrictions, countries with centralised alcohol sales provided a unique opportunity to study total domestic consumption during the pandemic without influence of private import or reliance on self-reports.

Aims: We examined the correlation between alcohol sales and national COVID-19 restrictions in three such countries, Finland, Norway and Sweden.

Method: We conducted this study as a mirror image study, comparing alcohol sales during the first 2 years of the COVID-19 pandemic with the two preceding years. We explored hours of daylight/season as potential confounders.

Results: We found no relevant change in alcohol sales during the pandemic years for Finland or Sweden. For Norway, there was a level-change in sales, which could be explained by decreased imports. Sales followed a seasonal pattern. In all three countries, the initial pandemic increase in alcohol sales coincided with an underlying annually recurring seasonal variation.

Conclusions: The COVID-19 pandemic had less of an impact on alcohol consumption in the three Nordic countries than could intuitively be expected. The increase of alcohol sales at the beginning of the COVID-19 pandemic coincided with a seasonal rise following a pre-pandemic pattern. Therefore, caution should be exercised with drawing conclusions from data with a short time perspective to avoid attribution bias.

Background: Reports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large.

Aim: To compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years.

Methods: We compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population.

Results: The overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50–1.83; p < 0.001) for individuals with SMD versus individuals without SMD. The corresponding RRs were 3.25 (CI 2.84–3.71; p < 0.001) for individuals with psychotic disorder, 1.06 (CI 0.88–1.26; p = 0.54) for individuals with bipolar disorder, and 1.03 (CI 0.80–1.32; p = 0.80) for individuals with severe depression. Compared to their respective counterparts in the non-SMD group, in the psychotic disorder and severe depression group, the RR were higher in women than in men. In the bipolar disorder group, the RR was higher in men than in women. The RR of COVID-19-associated death was generally higher in younger individuals with SMD. Individuals with psychosis between 18 and 59 years had the highest RR of COVID-19-associated death with 7.25 (CI 4.54–11.59; p<0.001).

Conclusions: Individuals with SMD, and particularly those with psychotic disorders, had a higher risk of COVID-19-associated death than the general population. As this is a pattern also seen with other infections, people with SMD may be similarly vulnerable in future pandemics.

Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke's encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.