Patients with major depressive disorder (MDD) who have inadequate responses to antidepressants (ADs) can benefit from augmentation with atypical antipsychotics (AAs). Cariprazine, a D3/D2 receptor partial agonist, is approved for schizophrenia and for manic, mixed, or depressive episodes associated with bipolar I disorder. Cariprazine is also currently under investigation for the adjunctive treatment of MDD. The aim of this retrospective cohort study was to describe healthcare resource utilization (HCRU) and associated medical costs with cariprazine and other adjunctive AA therapies for MDD.

IBM® MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Medicaid databases were searched for claims made from 01-Jan-2018 to 31-Mar-2021. The study population included adults (≥18 years) who met the following criteria: ≥1 inpatient claim with an MDD diagnosis or ≥2 outpatient claims that were >30 days apart; ≥1 AD therapy after MDD diagnosis; ≥1 branded or generic adjunctive AA (with AD); enrollment for ≥6 and ≥12 months for baseline and follow-up analyses, respectively. Branded AAs were analyzed individually; generic AAs were grouped. MDD-related HCRU outcomes per person over the 12-month follow-up period included inpatient stays, inpatient costs, office visits, and office visit costs, with adjusted pairwise comparisons between cariprazine and other AAs. Statistical significance was defined as the 95% confidence interval (CI) for the estimated mean ratio (EMR) of comparator AA to cariprazine not including 1 (i.e., value indicating no difference).

Analyses included 46,197 patients, with AA cohorts as follows: generics (n=39,410, including mostly aripiprazole and quetiapine); brexpiprazole (n=3,249); lurasidone (n=1,795); cariprazine (n=1,051); quetiapine-XR (n=644). A majority of patients across cohorts were women (range, 65.7% to 75.4%). Inpatient stays were statistically significantly fewer with cariprazine than all other AA therapies (EMR range [95% CI]: 1.7 [1.2–2.3] to 2.9 [2.1–3.9] for brexpiprazole and generics, respectively). Inpatient costs were lower for cariprazine than other branded AAs and statistically significantly lower compared to generics (2.4 [1.6–4.1]). Office visits were fewer with cariprazine than all other AAs and significantly lower than generics (1.1 [1.03–1.2]), lurasidone (1.3 [1.2–1.4]), and brexpiprazole (1.4 [1.2–1.5]). Office visit costs were also lower for cariprazine than all other AAs and statistically significantly lower than lurasidone (1.2 [1.03–1.5) and brexpiprazole (1.4 [1.2–1.6]).

The results of this study suggest that in patients with MDD, adjunctive treatment with cariprazine is associated with statistically significantly lower HCRU for certain outcomes and numerically lower medical costs compared to other branded AAs, along with statistically significantly lower HCRU and medical costs versus generic Aas.

AbbVie

Quantitative susceptibility mapping (QSM) demonstrates elevated iron content in Parkinson’s disease (PD) patients within the basal ganglia, though it has infrequently been studied in relation to gait difficulties including freezing of gait (FOG). Our purpose was to relate QSM of basal ganglia and extra-basal ganglia structures with qualitative and quantitative gait measures in PD.

This case–control study included PD and cognitively unimpaired (CU) participants from the Comprehensive Assessment of Neurodegeneration and Dementia study. Whole brain QSM was acquired at 3T. Region of interests (ROIs) were drawn blinded manually in the caudate nucleus, putamen, globus pallidus, pulvinar nucleus of the thalamus, red nucleus, substantia nigra, and dentate nucleus. Susceptibilities of ROIs were compared between PD and CU. Items from the FOG questionnaire and quantitative gait measures from PD participants were compared to susceptibilities.

Twenty-nine participants with PD and 27 CU participants were included. There was no difference in susceptibility values in any ROI when comparing CU versus PD (p > 0.05 for all). PD participants with gait impairment (n = 23) had significantly higher susceptibility in the putamen (p = 0.008), red nucleus (p = 0.01), and caudate nucleus (p = 0.03) compared to those without gait impairment (n = 6). PD participants with FOG (n = 12) had significantly higher susceptibility in the globus pallidus (p = 0.03) compared to those without FOG (n = 17). Among quantitative gait measures, only stride time variability was significantly different between those with and without FOG (p = 0.04).

Susceptibilities in basal ganglia and extra-basal ganglia structures are related to qualitative measures of gait impairment and FOG in PD.

Surgical management is the mainstay of treatment for tumours in the parapharyngeal space. This study aimed to evaluate the indications, limits and technical nuances of the endoscopic transoral approach.

Thirteen patients with parapharyngeal space tumours that were treated between May 2017 and November 2020 were included in this retrospective study.

All patients underwent surgery for complete oncological resection except one patient who received treatment for diagnostic purposes. No major complications were reported, with excellent control of the vital structures of the parapharyngeal space.

The endoscopic transoral approach to the parapharyngeal space is a promising alternative approach for selected parapharyngeal space tumours with satisfactory outcomes.

To summarise and describe the clinical presentations, diagnostic approaches and airway management techniques in children with laryngotracheal trauma.

The clinical data related to laryngotracheal trauma diagnosed and treated at the Beijing Children's Hospital, between January 2013 and July 2018, were retrospectively reviewed. Disease diagnosis, treatment, management and outcomes were analysed.

A total of 13 cases were enrolled, including 7 cases of penetrating laryngotracheal trauma. The six cases of blunt laryngotracheal trauma were caused by collisions with hard objects. In all cases, voice, airway and swallowing outcomes were graded as ‘good’, except for one patient who had residual paralysis of the vocal folds.

Flexible fibre-optic laryngoscopy and computed tomography can play an important role in diagnosing laryngotracheal trauma. The airway should be secured and, if necessary, opened by tracheal intubation or tracheostomy.

Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.

To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).

The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22–1.45; p = 5.03 × 10−11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25–1.37; p = 6.88 × 10−31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23–1.40; p = 1.42 × 10−16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03–1.10, p = 7.85 × 10−4 for PTSD; OR = 1.37, 95% CI 1.14–1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.

Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.

This study aimed to elucidate whether molecular signalling involved in upper airway remodelling is enhanced in patients with obstructive sleep apnoea.

Twenty patients with mild obstructive sleep apnoea (control group) and 40 patients with moderate to severe obstructive sleep apnoea (obstructive sleep apnoea group) who desired uvulopalatopharyngoplasty were recruited for the study. After uvulopalatopharyngoplasty, surgical specimens of the uvula were subjected to haematoxylin and eosin, Masson's trichrome and immunohistochemical staining. Western blot and reverse transcriptase-polymerase chain reaction were used to evaluate the protein and messenger RNA expressions.

The obstructive sleep apnoea group showed more severe inflammation, increased collagen deposition and higher immunohistochemical staining intensity for TGF-ß and MMP-9 as well as higher protein and messenger RNA expression of MMP-9, VEGF, TGF-ß, p38 MAPK, SMAD 2/3, AKT and JNK in the uvula than control group.

Patients with obstructive sleep apnoea demonstrated more severe inflammation, increased airway remodelling, and increased protein and messenger RNA expression of pro-inflammatory and pro-fibrotic cytokines in the uvula than control participants.

This study aimed to investigate the association of nasal nitric oxide and olfactory function.

A cross-sectional study was performed in 117 adults, including 91 patients with chronic rhinosinusitis and 26 healthy controls. Scores on the 22-item Sino-Nasal Outcomes Test, Lund-Mackay scale and Lund-Kennedy scale were recorded to assess severity of disease. All participants were screened for common inhaled and food allergens. Nasal nitric oxide and fractional exhaled nitric oxide testing, acoustic rhinometry and anterior rhinomanometry testing were performed to measure nasal function. The validated Sniffin’ Sticks test battery was used to assess olfactory function.

Higher nasal nitric oxide was an independent protective factor for odour discrimination and odour threshold in participants with chronic rhinosinusitis after adjusting for age, gender, drinking, smoking, 22-item Sino-Nasal Outcomes Test, Lund-Mackay score, Lund-Kennedy score, immunoglobulin E and the second minimal cross-sectional area by acoustic rhinometry. Nasal nitric oxide also showed high discrimination in predicting impaired odour discrimination. In addition, nasal nitric oxide was lower in older participants, those with higher Lund-Mackay or Lund-Kennedy scores and higher with elevated total serum immunoglobulin E concentrations above a threshold of 0.35 kU/l.

Higher nasal nitric oxide is associated with better odour discrimination in chronic rhinosinusitis and is modulated by age, degree of allergy and severity of chronic rhinosinusitis.

The aim of the present study was to perform a retrospective review of the lesion sites in congenital middle-ear cholesteatoma and any accompanying ossicular defects, as well as to explore the possible aetiology of congenital middle-ear cholesteatoma associated with such ossicular chain defects.

The clinical characteristics and pathogenic mechanisms of ossicular chain defects were investigated in 10 patients with early-stage congenital middle-ear cholesteatoma confirmed by surgery, from August 2011 to February 2019.

Monofocal cholesteatoma was located in the anterosuperior quadrant in 3 cases and in the posterosuperior quadrant in 7 cases; all 10 cases showed an absence of the long crus of incus, and 8 cases showed a complete or partial absence of stapes superstructure. The lesions were confined to the vestibular window and the stapes region and had no contact with the long crus of the incus or stapes in nine cases. None of the 10 patients had any recurrence of cholesteatoma.

Although cholesteatoma can cause erosion of ossicles, the present cases suggest that residual epithelium of the cholesteatoma may coexist with ossicular malformations. Therefore, the aetiology of the clinical characteristics in these patients may derive from residual epithelial hinderance of ossicle development.

In China, the indications of paliperidone extended in schizophrenia adolescents (12-17 years) was approved by National Medical Products Administration (NMPA) in 2017. But, the utilization of paliperidone in this group needs to be further investigated.

To assess paliperidone utilization in schizophrenia adolescents.

The study employed the electronic medical records (EMRs) database from a psychiatry specialized hospital (PH) and a general hospital (GH), respectively. General information, including birth date, gender, visit date, diagnosis (inpatient and outpatient) with ICD-10 coding, drug characterize, prescription date and dosage, was de-identified and standardized for analysis. Schizophrenia adolescents (ICD-10: F20.x) received at least one prescription of paliperidone between 2018 and 2019 were included in this study. Index date was defined as the date of first identified paliperidone prescription. The patients were followed up until the end of 2019 with the last record, or upon reaching 18 years. The database was analyzed based on days of supply, administration frequency, and daily dose.

Overall, 112 and 117 eligible patients were included in the present study from PH and GH, respectively. The median drug supply was 179.0 days and 44.0 days, respectively, during which median number of prescriptions patients received was 6.0 and 3.0. Paliperidone was mostly initiated alone (57.1% and 88.9%) with frequency of once daily (97.3% and 88.9%), and the median of average daily dose during follow-up was 5.7 mg/day and 6.0 mg/day, respectively.

The duration of paliperidone usage was very different in two hospitals, but the dosages in both hospitals were generally agreed with prescribing information.