To describe inpatient fluoroquinolone use and susceptibility data over a 10-year period after the implementation of an antimicrobial stewardship program (ASP) led by an infectious diseases pharmacist starting in 2011.

Retrospective surveillance study.

Large community health system.

Fluoroquinolone use was quantified by days of therapy (DOT) per 1,000 patient days (PD) and reported quarterly. Use data are reported for inpatients from 2016 to 2020. Levofloxacin susceptibility is reported for Pseudomonas aeruginosa and Escherichia coli for inpatients from 2011 to 2020 at a 4 adult-hospital health system.

Inpatient fluoroquinolone use decreased by 74% over a 5-year period, with an average decrease of 3.45 DOT per 1,000 PD per quarter (P < .001). Over a 10-year period, inpatient levofloxacin susceptibility increased by 57% for P. aeruginosa and by 15% for E. coli. P. aeruginosa susceptibility to levofloxacin increased by an average of 2.73% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = −0.99 (P = .002). E. coli susceptibility to levofloxacin increased by an average of 1.33% per year (P < .001) and had a strong negative correlation with fluoroquinolone use, r = −0.95 (P = .015).

A substantial decrease in fluoroquinolone use and increase in P. aeruginosa and E. coli levofloxacin susceptibility was observed after implementation of an antimicrobial stewardship program. These results demonstrate the value of stewardship services and highlight the effectiveness of an infectious diseases pharmacist led antimicrobial stewardship program.

We summarize what we assess as the past year's most important findings within climate change research: limits to adaptation, vulnerability hotspots, new threats coming from the climate–health nexus, climate (im)mobility and security, sustainable practices for land use and finance, losses and damages, inclusive societal climate decisions and ways to overcome structural barriers to accelerate mitigation and limit global warming to below 2°C.

We synthesize 10 topics within climate research where there have been significant advances or emerging scientific consensus since January 2021. The selection of these insights was based on input from an international open call with broad disciplinary scope. Findings concern: (1) new aspects of soft and hard limits to adaptation; (2) the emergence of regional vulnerability hotspots from climate impacts and human vulnerability; (3) new threats on the climate–health horizon – some involving plants and animals; (4) climate (im)mobility and the need for anticipatory action; (5) security and climate; (6) sustainable land management as a prerequisite to land-based solutions; (7) sustainable finance practices in the private sector and the need for political guidance; (8) the urgent planetary imperative for addressing losses and damages; (9) inclusive societal choices for climate-resilient development and (10) how to overcome barriers to accelerate mitigation and limit global warming to below 2°C.

Science has evidence on barriers to mitigation and how to overcome them to avoid limits to adaptation across multiple fields.

ADHD patients often report that they are being flooded by sensory impressions. Studies investigating sensory processing show hypersensitivity for sensory inputs across the senses. While studying unimodal signal-processing is relevant and well-suited in a controlled laboratory environment, our daily interaction with our environment does not occur merely unimodal. A complex interplay of the senses is necessary to form a unified percept. In order to achieve this, the unimodal sensory modalities are bound together in a process called multisensory integration (MI).

In the current study we investigate MI in an adult ADHD sample accompanied by resting-state functional magnetic resonance imaging (RS-fMRI).

Twenty-five ADHD patients and twenty-four healthy controls were recruited. MI was examined using the McGurk effect, where - in case of successful MI - incongruent speech-like phonemes between visual and auditory modality are leading to a perception of a new phoneme. Mann-Whitney-U test was applied to assess statistical differences between groups. Resting-state functional MRI was acquired to realize a seed-to-voxel analysis

Susceptibility to MCGurk was significantly lowered for ADHD patients (ADHDMdn:5.83%, ControlsMdn:44.2%, U= 160.5, p=0.022, r=-0.34). When ADHD patients integrated phonemes, reaction times were significantly longer (ADHDMdn:1260ms, ControlsMdn:582ms, U=41.0, p<.000, r= -0.56). Seeded medio temporal gyrus was negatively associated in functional connectivity to primary auditory cortex, inferior frontal gyrus, precentral gyrus, and fusiform gyrus.

MI seems to be deficient for ADHD patients for stimuli that need late attentional allocation. This finding is supported for higher functional connectivity from unimodal sensory areas to polymodal, MI convergence zones for complex stimuli.

No significant relationships.

The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems and hospitals to rapidly modify standard practice, including antimicrobial stewardship services. Our study examines the impact of COVID-19 on the antimicrobial stewardship pharmacist.

A survey was distributed nationally to all healthcare improvement company members.

Pharmacist participants were mostly leaders of antimicrobial stewardship programs distributed evenly across the United States and representing urban, suburban, and rural health-system practice sites.

Participants reported relative increases in time spent completing tasks related to medication access and preauthorization (300%; P = .018) and administrative meeting time (34%; P = .067) during the COVID-19 pandemic compared to before the pandemic. Time spent rounding, making interventions, performing pharmacokinetic services, and medication reconciliation decreased.

A shift away from clinical activities may negatively affect the utilization of antimicrobials.

Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Poor transition planning contributes to discontinuity of care at the child–adult mental health service boundary (SB), adversely affecting mental health outcomes in young people (YP). The aim of the study was to determine whether managed transition (MT) improves mental health outcomes of YP reaching the child/adolescent mental health service (CAMHS) boundary compared with usual care (UC).

A two-arm cluster-randomised trial (ISRCTN83240263 and NCT03013595) with clusters allocated 1:2 between MT and UC. Recruitment took place in 40 CAMHS (eight European countries) between October 2015 and December 2016. Eligible participants were CAMHS service users who were receiving treatment or had a diagnosed mental disorder, had an IQ ⩾ 70 and were within 1 year of reaching the SB. MT was a multi-component intervention that included CAMHS training, systematic identification of YP approaching SB, a structured assessment (Transition Readiness and Appropriateness Measure) and sharing of information between CAMHS and adult mental health services. The primary outcome was HoNOSCA (Health of the Nation Outcome Scale for Children and Adolescents) score 15-months post-entry to the trial.

The mean difference in HoNOSCA scores between the MT and UC arms at 15 months was −1.11 points (95% confidence interval −2.07 to −0.14, p = 0.03). The cost of delivering the intervention was relatively modest (€17–€65 per service user).

MT led to improved mental health of YP after the SB but the magnitude of the effect was small. The intervention can be implemented at low cost and form part of planned and purposeful transitional care.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Age-of-onset (AO) seems to be a phenotypic variable with a strong genetic component and therefore useful in molecular analysis of bipolar disorder (BP). A debate about the cut-off point for defining early AO has developed over the last few years. Using an Expectation-Maximization algorithm Bellivier et al. (2001) found the best fit for a model with three onset-groups, proposing the age 20-21 as cut-off for early onset, while using the same algorithm Kennedy et al. (2005) found the best fit for a two onset-group model with age 40 as cut-off with an incidence peak for mania in the age-band 21-25. Based on segregation analysis, we proposed a two AO-group model with cut-off age 25 for early onset (Grigoroiu-Serbanescu et al. 2001). The present study aimed at investigating the best AO-model in 500 Romanian BPI and 1458 German BPI patients using commingling analysis (SAGEv6.01-software) (Elston et al, 2009). The best model was selected according to Akaike's Information Criterion (AIC).

The two AO-group and three AO-group models provided similar AIC-values both in the Romanian and the German sample. The Romanian early-onset group (40% cases) had means around 18 years, SDs=6-7, while in the German early-onset group the mean AO was around 20 years (SDs=9-11) (50% cases). Thus the cut-off for early-onset (X +1SD) was different.

Our results overlapped with the findings of Kennedy et al (2005) showing that two-curve and three-curve AO mixtures similarly fit the AO-distribution in BPI disorder and the cut-offs for early-onset differ by sample.

To evaluate open-label treatment with olanzapine in patients with borderline personality disorder (BPD).

In two concurrent studies, patients received 12 weeks of open-label olanzapine after completing 12-weeks of double-blind treatment with either olanzapine or placebo. Open-label olanzapine dosing started at 2.5 or 5mg/day and could be increased up to 20mg/day (Study 1) or 15mg/day (Study 2).

Mean ZAN-BPD total scores decreased from approximately 17 points to approximately 8-10 points during the acute phase. After 12 weeks of open-label olanzapine treatment, mean ZAN-BPD total scores were approximately 6-7 points. Patients treated with placebo during the acute phase and then open-label olanzapine showed changes in weight, prolactin, and other laboratory values similar in magnitude to those seen in acutely olanzapine-treated patients. Patients treated with olanzapine during the acute phase showed smaller changes in weight and laboratory values during the open-label extension.

Overall BPD symptom severity was low by the end of the open-label olanzapine treatment period. The types of treatment emergent adverse events appeared to be consistent with those seen previously in patients treated with olanzapine. The direction and magnitude of effects on safety measures depended on the treatment received during the prior double-blind period.