Central nervous system (CNS)-active polypharmacy is frequent and potentially harmful in older patients. Data on its burden outside the USA and European countries remain limited.

To estimate the period prevalence of and factors associated with out-of-hospital CNS-active polypharmacy in older adults.

We used data from a cohort of out-patients aged ≥60 years affiliated to the Hospital Italiano de Buenos Aires’ health maintenance organisation on 1 January 2021. A CNS-active polypharmacy event was defined as the concurrent exposure to ≥3 CNS-active medications (i.e. antidepressants, anti-epileptics, antipsychotics, benzodiazepines, Z-drugs and opioids) through filled out-of-hospital prescriptions. We calculated the period prevalence of CNS-active polypharmacy for 2021. We identified factors associated with CNS-active polypharmacy using a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals (CI).

We included 63 857 patients. Pre-existing mental health diagnoses included anxiety (21%), depressive (14%) and sleep (11%) disorders. CNS-active polypharmacy occurred in 4535 patients, for a period prevalence of 7.1% (95% CI: 6.9–7.3%). The combination of an antidepressant, an antipsychotic and a benzodiazepine accounted for 21% of the CNS-active polypharmacy events. Frontotemporal dementia (odds ratio: 14.67; 95% CI: 4.47–48.20), schizophrenia (odds ratio: 7.93; 95% CI: 4.64–13.56), bipolar disorder (odds ratio: 7.20; 95% CI: 5.45–9.50) and depressive disorder (odds ratio: 3.50; 95% CI: 3.26–3.75) were associated with CNS-active polypharmacy.

One in 14 adults aged 60 years and older presented out-of-hospital CNS-active polypharmacy. Future studies should evaluate measures to reduce CNS-active medication use in this population.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

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.

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.

To describe our management of implantable hearing device extrusion in cases of previous cervicofacial surgery.

A review was conducted of a retrospectively acquired database of surgical procedures for implantable hearing devices performed at our department between January 2011 and December 2019. Cases of device extrusion and previous cervicofacial surgery are included. Medical and surgical management is discussed.

Four cases of implant extrusion following cervicofacial surgery were identified: one involving a Bonebridge system and three involving cochlear implants. In all cases, antibiotic treatment was administered and surgical debridement performed. The same Bonebridge system was implanted in the middle fossa. The three cochlear implants were removed, and new devices were implanted in a more posterior region.

Previous cervicofacial surgery is a risk factor for hearing implant extrusion. The middle fossa approach is the best option for the Bonebridge system. Regarding the cochlear implant, it is always suitable to place it in a more posterior area. An inferiorly based fascio-muscular flap may be a good option to reduce the risk of extrusion.

Safe cochlear implantation is challenging in patients with canal wall down mastoid cavities, and the presence of large meatoplasties increases the risk of external canal overclosure. This paper describes our results of obliteration of the mastoid cavity with conchal cartilage as an alternative procedure in cases of canal wall down mastoidectomy with very large meatoplasty.

The cases of seven patients with a canal wall down mastoidectomy cavity who underwent cochlear implantation were retrospectively reviewed. Post-operative complications were analysed. The mean follow-up duration was 4.5 years.

There was no hint of cholesteatoma recurrence and all patients have been free of symptoms during follow up. Only one patient showed cable extrusion six months after surgery, and implantation of the contralateral ear was needed.

Pseudo-obliteration of the mastoid cavity with a cartilage multi-layered palisade reconstruction covering the electrode may be a safe alternative in selected patients with a large meatoplasty.

Bipolar disorder (BD) is related to high prevalence of somatic comorbidities, health care costs, and premature mortality [1]. Some evidence supports the view of BD as chronic, progressive and multisystem disorder in which not only mental system, but also somatic systems are involved [2].

To investigate differences in physical health in patients with bipolar disorder at different stages (early vs. late) of the disease.

Cross-sectional, naturalistic, multicenter study. Sample: 110 outpatients with BD [68 early stage (diagnosed at least 5 years earlier) and 42 late stage (at least 20 years earlier)]. Assessment: demographic and clinical variables; psychopathology: HDRS, YMRS and CGI; biological information: anthropometric, vital signs and lab results.

Early stage group: mean age 40.1 (11.9), 66.2% females and CGI = 3.6 (1.4). Late stage group: mean age 55.8 (8.2), 69.0% females and CGI = 4.0 (1.4). Patients in early stage have significantly higher levels of glucose (t = −4.007, P < 0.001), urea (t = −2.724, P = 0.008), creatinine (F = 0.560, P = 0.022), triglycerides (t = −3.501, P = 0.001), Fe (t = 2.871, P = 0.005) and insulin (t = −3.223, P = 0.002). Moreover, they have higher Body Max Index (BMI) (t = −3.728, P < 0.000), abdominal circumference (t = −4.040, P < 0.000) and greater number of somatic comorbidities (t = −2.101, P = 0.041).

– patients with bipolar disorders in late stages have worse physical health than those in early stage.

– these results could be an indication that bipolar disorder might better viewed as a multisystem disorder.

The authors have not supplied their declaration of competing interest.

The indications for expanded endoscopic transnasal approaches continue to increase, with more complex skull base defects needing to be repaired. This study reviews the management of large anterior skull base defects with opening of the sellar diaphragm.

A prospective analysis of endonasal endoscopic surgery carried out at Son Espases University Hospital between January 2013 and December 2018 was performed. The analysis included only the cases with a significative intra-operative cerebrospinal fluid leak. In all cases, reconstruction was performed by combining the gasket seal technique with a pedicled mucosal endonasal flap.

Twenty-eight patients were included. The mucoperiosteal nasoseptal flap, the lateral wall flap and the middle turbinate flap were used in 13, 8 and 7 patients, respectively, combined with the gasket seal technique. One case of post-operative cerebrospinal fluid leak was observed (3.57 per cent).

The combination of a gasket seal with an endonasal mucosal flap is an excellent technique for repairing large anterior skull base defects.

The transmastoid pre-sigmoid approach is always the preferred choice for implantation of the Bonebridge active bone conduction system in patients with a normal anatomy. When an anatomical variant exists or a previous surgery has been performed, a retrosigmoid approach or middle fossa approach can be performed.

The preferred surgical technique for a middle fossa approach is described. A 14 mm drill head (Neuro Drill) was used to create the bed at the squamous portion of the temporal bone. Surgical time and complication rate were analysed.

The surgical time was shorter than 30 minutes in all cases, and only 14 seconds were needed to create a 14 mm bone bed. No complications were observed during the follow-up period (6–45 months).

Use of the Neuro Drill for the middle fossa approach is an easy technique. It significantly decreases the surgical time, without increasing the complication rate.