Deep brain stimulation may be a viable option for resistant to treatment aggression in children with intellectual disability

Introduction

Deep brain stimulation (DBS) is a surgical technique used to manage aggression in patients who do not improve despite the use of appropriate drug treatment.

Objective

The objective of this study is to assess the impact of DBS on aggressive behavior refractory to the pharmacological and behavioral treatment of patients with Intellectual Disabilities (ID).

Methods

A follow-up was conducted on a cohort of 12 patients with severe ID, undergoing DBS in posteromedial hypothalamic nuclei; evaluated with the Overt Aggression Scale (OAS), before the intervention, at 6, 12, and 18 months of medical follow-up.

Results

After the surgical procedure, there was a significant reduction in the aggressiveness of patients in the follow-up medical evaluation at 6 months (t = 10.14; p < 0.01), 12 months (t = 14.06; p < 0.01), and 18 months (t = 15.34; p < 0.01), respect to the initial measurement; with a very large effect size (6 months: d = 2.71; 12 months: d = 3.75; 18 months: d = 4.10). From 12 months onward, emotional control stabilized and is sustained at 18 months (t = 1.24; p > 0.05).

Conclusion

DBS in posteromedial hypothalamic nuclei may be an effective treatment for the management of aggression in patients with ID refractory to pharmacological treatment.     

Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial

Objective

This study compares efficacy and safety of divalproate extended release (DVA‐ER) and amitriptyline (AMT) in migraine .

Materials and methods

Three hundred migraineurs having >4 attacks monthly were randomized into DVA‐ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events.

Results

The median age was 32 years, and 241 were women. 150 patients each received DVA‐ER and AMT. At 3 months, 74.7% in DVA‐ER and 62% patients in AMT group improved in headache frequency (P = 0.02) and at 6 months, 65.3% and 54%, respectively (P = 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA‐ER and 64% in AMT (P = 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; P = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA‐ER group.

Conclusion

Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis.     

Impact of falls on depressive symptoms among the oldest old: Results from the AgeQualiDe study

Objective

The purpose of this study was to examine the impact of falls on depressive symptoms among the oldest old in Germany longitudinally.

Methods

Data were used from 2 waves of the multicenter prospective cohort “Study on needs, health service use, costs and health‐related quality of life in a large sample of oldest‐old primary care patients (85+)” (AgeQualiDe). This study covers primary care patients ≥85 years (at baseline: n = 547, average age of 88.9 ± 3.0 years; ranging from 85 to 100 years). General practitioner‐diagnosed falls were used as explanatory variable. The Geriatric Depression Scale was used as outcome measure.

Results

Linear fixed effects regressions showed that the occurrence of falls is associated with an increase in depressive symptoms (β = .60, P = .02), whereas changes in marital status, ageing, social support, functional decline (instrumental activity of daily living), cognitive impairment, and an increase in chronic diseases did not affect depressive symptoms. In sensitivity analysis, an increase in depressive symptoms was associated with functional impairment (basic activities of daily living; Barthel index; β = ?.04, P = .005).

Conclusions

Based on a large, population‐based longitudinal study, this study underlined the impact of falls on depressive symptoms and consequently extended previous knowledge about an association between falls and depressive symptoms in the oldest old. Developing strategies to prevent falls might also help to prevent depressive symptoms.     

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Objective

No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.

Methods

Articles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.

Results

Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).

Conclusion

The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.     

Speech and gait abnormalities in motor subtypes of de-novo Parkinson's disease

Aim

To investigate the presence and relationship of temporal speech and gait parameters in patients with postural instability/gait disorder (PIGD) and tremor-dominant (TD) motor subtypes of Parkinson's disease (PD).

Methods

Speech samples and instrumented walkway system assessments were acquired from a total of 60 de-novo PD patients (40 in TD and 20 in PIGD subtype) and 40 matched healthy controls. Objective acoustic vocal assessment of seven distinct speech timing dimensions was related to instrumental gait measures including velocity, cadence, and stride length.

Results

Compared to controls, PIGD subtype showed greater consonant timing abnormalities by prolonged voice onset time (VOT) while also shorter stride length during both normal walking and dual task, while decreased velocity and cadence only during dual task. Speaking rate was faster in PIGD than TD subtype. In PIGD subtype, prolonged VOT correlated with slower gait velocity (r = −0.56, p = 0.01) and shorter stride length (r = −0.59, p = 0.008) during normal walking, whereas relationships were also found between decreased cadence in dual task and irregular alternating motion rates (r = −0.48, p = 0.04) and prolonged pauses (r = −0.50, p = 0.03). No correlation between speech and gait was detected in TD subtype.

Conclusion

Our findings suggest that speech and gait rhythm disorder share similar underlying pathomechanisms specific for PIGD subtype.     

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n₁ = 51, n₂ = 101), corticobasal degeneration (CBD) (n₁ = 11, n₂ = 3), progressive supranuclear palsy (PSP) (n₁ = 22, n₂ = 21), multiple system atrophy (MSA) (n₁ = 31, n₂ = 26), and healthy control (HC) (n₁ = 48, n₂ = 30) participants, as well as Alzheimer's disease (AD) (n₂ = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease

Background

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [¹²³I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

Objectives

To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.

Methods

We assessed clinical features, the peripheral immune profile, and striatal [¹²³I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort).

Results

A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: β = −0.01, p < 0.001; PPMI-cohort: β = −0.05, p = 0.05) and the putamen (primary-cohort: β = −0.05, p = 0.02; PPMI-cohort: β = −0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: β = +0.09, p < 0.05; PPMI-cohort: β = +0.11, p = 0.02) and the putamen (primary-cohort: β = +0.09, p < 0.05, PPMI-cohort: β = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: β = −0.05, p = 0.02; PPMI-cohort: β = 0, p = 0.94; putamen; primary-cohort: β = −0.04, p = 0.08; PPMI-cohort: β = −0.01, p = 0.73).

Conclusions

Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Evaluation of the implementation of the Meeting Centres Support Program in Italy,Poland, and the UK; exploration of the effects on people with dementia

Objectives

MEETINGDEM investigated whether the Dutch Meeting Centres Support Programme (MCSP) could be implemented in Italy, Poland, and the UK with comparable benefits. This paper reports on the impact on people living with dementia attending pilot Meeting Centres in the 3 countries.

Methods

Nine pilot Meeting Centres (MCs) participated (Italy—5, Poland—2, UK—2). Effectiveness of MCSP was compared with Usual Care (UC) on outcomes measuring behavioural and psychological symptoms (NPI), depression (CSDD), and quality of life (DQoL, QOL‐AD), analysed by ANCOVAs in a 6‐month pre‐test/post‐test controlled trial.

Results

Pre/post data were collected for 85 people with dementia and 93 carers (MCSP) and 74 people with dementia /carer dyads' receiving UC. MCSP showed significant positive effects for DQoL [Self‐esteem (F = 4.8, P = 0.03); Positive Affect (F = 14.93, P < 0.00); Feelings of Belonging (F = 7.77, P = 0.01)] with medium and large effect sizes. Higher attendance levels correlated with greater neuropsychiatric symptom reduction (rho = 0.24, P = 0.03) and a greater increase in feelings of support (rho = 0.36, P = 0.001).

Conclusions

MCSPs showed significant wellbeing and health benefits compared with UC, building on the evidence of effectiveness from the Netherlands. In addition to the previously reported successful implementation of MCSP in Italy, Poland, and the UK, these findings suggest that further international dissemination of MCSP is recommended.     

Stress and coping mechanisms among adolescents living in orphanages: An experience from Klang Valley,Malaysia

Introduction

Health issues often differ from one population to another. Assessing different aspects of the health condition is a vital step toward developing and designing appropriate prevention and treatment programs to reduce health problems in any group or population. This study aimed to assess both the prevalence of stress and the coping mechanisms as well as identify the predictors of stress levels among adolescents in Malaysian orphanages.

Methods

Overall, 307 male and female adolescents (aged 13‐18 y old) living in 9 private orphanages located in Klang Valley, Malaysia, participated in this cross‐sectional study. Brief COPE scale and Depression, Anxiety and Stress Scale‐21 were used as the main instruments in the current study.

Results

The results of the current study showed female adolescents and participants with a higher level of education were more likely to experience stress. The results also showed significant differences between boys and girls in using of coping mechanisms in self‐distraction (t = ?2.39, P = .01), substance use (t = 2.12, P = .03), use of emotional support (t = ?2.70, P = .001), humor (t = 2.28, P = .02), and religion (t = ?2.19, P = .02). Denial, venting, religion, humor, planning, and active coping were identified as predictors of stress among participants.

Discussion

The results showed a high prevalence of stress and a negative coping pattern among participants. The finding of the current study also showed the urgency of taking immediate action to reduce stress and improve coping methods among Malaysian institutional adolescents.     

Development of a short form of the Attitudes to Ageing Questionnaire (AAQ)

Objectives

The original 24‐item Attitudes to Aging Questionnaire (AAQ) is well established as a measure of attitudes to aging, comprising domains of psychosocial loss (PL), physical change (PC), and psychological growth (PG). This paper presents a new 12‐item short form Attitudes to Aging Questionnaire (AAQ‐SF).

Methods

The original field trial data used to develop the 24‐item AAQ (AAQ‐24) were used to compare 6‐item, 9‐item, and 12‐item versions of AAQ‐SF (sample 1, n = 2487) and to test the discriminative validity of the selected 12‐item AAQ‐SF (sample 2, n = 2488). Data from a separate study reporting on the AAQ‐24 (sample 3, n = 792) verified the analyses.

Results

The 12‐item AAQ‐SF reported adequate internal consistency in both sample 1 (PL α = .72, PC α = .72, and PG α = .62) and sample 3 (PL α = .68, PC α = .73, and PG α = .61). The AAQ‐SF functioned consistently with the profile of the AAQ‐24 in that subscales in both formats of this measure discriminate between respondents on key parameters such as depression, subjective health status, and overall quality of life in sample 2. Sample 3 also demonstrated the AAQ‐SF can detect the differences in attitudes toward aging between individuals experiencing anxiety and depression and those without psychological symptoms. Confirmatory factor analysis confirmed that the structure of the AAQ‐SF mirrors that of the original 24‐item AAQ.

Conclusions

The AAQ‐SF is a robust measure of attitudes toward aging, which can reduce respondent burden when used within longer questionnaire batteries or longitudinal research. Copyright © 2017 John Wiley & Sons, Ltd.     

Analysis of positron emission tomography hypometabolic patterns and neuropsychiatric symptoms in patients with dementia syndromes

Aims

To estimate the proportions of specific hypometabolic patterns and their association with neuropsychiatric symptoms (NPS) in patients with cognitive impairment (CI).

Methods

This multicenter study with 1037 consecutive patients was conducted from December 2012 to December 2019. ¹⁸F-FDG PET and clinical/demographic information, NPS assessments were recorded and analyzed to explore the associations between hypometabolic patterns and clinical features by correlation analysis and multivariable logistic regression models.

Results

Patients with clinical Alzheimer's disease (AD, 81.6%, 605/741) and dementia with Lewy bodies (67.9%, 19/28) mostly had AD-pattern hypometabolism, and 76/137 (55.5%) of patients with frontotemporal lobar degeneration showed frontal and anterior temporal pattern (FT-P) hypometabolism. Besides corticobasal degeneration, patients with behavioral variant frontotemporal dementia (36/58), semantic dementia (7/10), progressive non-fluent aphasia (6/9), frontotemporal lobar degeneration and amyotrophic lateral sclerosis (3/5), and progressive supranuclear palsy (21/37) also mostly showed FT-P hypometabolism. The proportion of FT-P hypometabolism was associated with the presence of hallucinations (R = 0.171, p = 0.04), anxiety (R = 0.182, p = 0.03), and appetite and eating abnormalities (R = 0.200, p = 0.01) in AD.

Conclusion

Specific hypometabolic patterns in FDG-PET are associated with NPS and beneficial for the early identification and management of NPS in patients with CI.     

The association between transient childhood psychotic experiences and psychosocial outcomes in young adulthood: Examining the role of mental disorders and adult attachment

Aim

Evidence suggest individuals with mental disorders and psychotic experiences (PE), even transient PE, show poorer psychosocial outcomes relative to those with mental disorders. The concept of “attachment” is hypothesized as the mechanism by which people seek support in times of need. This can be measured as discrete styles or as positive (low avoidance/anxiety)/negative (high avoidance/anxiety) dimensions. Adult attachment has previously been examined on PE risk factors, but not outcomes. This study aimed to examine the relationship between transient childhood PE and adult psychosocial outcomes, comparing those with and without mental disorders. Second, to examine the role of adult attachment.

Method

Participants (n = 103) attended baseline (age 11–13) and 10-year follow-up. PE and mental disorders were measured using the Schedule for Affective Disorders and Schizophrenia for School-aged Children. Attachment and outcomes were measured using self-report measures. Analysis compared those with PE (with/without mental disorders), and mental disorders without PE, to controls, using linear and Poisson regression.

Results

PE was associated with lower self-esteem (β = −2.28, p = .03), perceived social support from friends (β = −2.80, p = .01), and higher stress in platonic relationships (IRR = 1.64). PE and mental disorders were associated with lower self-esteem (β = −5.74, p = .002), higher stress in romantic (IRR = 1.40) and platonic (IRR = 1.59) relationships, general stress (β = 5.60, p = .006), and mental distress (β = 5.67, p = .001). Mental disorders alone was not associated with any measure. Adult attachment dimensions attenuated some results.

Conclusions

This paper illustrates the association between transient PE and adult psychosocial outcomes, with & without co-occurring mental disorders, and demonstrates the role of adult attachment.     

Correlations between psychopathology and self‐reported quality of life among adolescents in youth correctional facilities in Lagos,Nigeria: A short report

Background

The relationship between psychopathology and quality of life (QoL) and well‐being among young incarcerated offenders has hardly been explored.

Aims

Our aim was to test the hypothesis that higher self‐rated psychopathology would be associated with lower QoL among adolescents resident within youth correctional facilities in Lagos.

Methods

Psychopathology was assessed using the Strength and Difficulty Questionnaire (SDQ), while QoL was measured by using the Paediatric Quality of Life .

Results

One hundred and sixty‐five adolescents completed the study, mostly boys (n = 124; 75%) with a mean age of 14.3 ± 2.1 years. Nearly, a fifth (30, 18%) of respondents had abnormal total SDQ scores (≥17), suggestive of definite psychiatric disorder, while another 44 (27%) had highly probable psychopathology (total SDQ scores 15–16). There was strong negative correlation (r = ?0.51, p < 0.001) between total SDQ scores and overall self‐reported QoL among respondents.

Conclusions and implications for practice

Although we were unable to infer direction of relationship between psychopathology and QoL among these adolescents, it is plausible to suppose that treatment of mental health problems could have a positive impact on rehabilitation and reintegration. Given the rate of likely psychopathology, mental health screening within young offender institutions should be routine, and followed, as necessary with full assessment and resultant treatment. Copyright © 2017 John Wiley & Sons, Ltd.     

Joint hypermobility is also associated with anxiety disorders in the elderly population

Background

Anxiety disorders (AD) are very prevalent in the elderly, tend to compromise quality of life, and generate substantial costs. Considering that the prevention and early detection of anxiety may be relevant to increase health gains in older adults, it would be of great interest to identify whether the joint hypermobility syndrome (JHS) is also related to anxiety disorders in this age range.

Methods

Cross‐sectional data was collected in a sample of 108 subjects in a rural town in Spain. Instruments included Spielberger STAI, a modified Wolpe Fear Survey Schedule, General health Questionnaire (GHQ)‐28, and the anxiety and mood disorders section of the SCID, to assess past year prevalence of anxiety disorders. JHS was evaluated by trained examiners using the “Hospital del Mar criteria”.

Results

Among the 108 subjects (55% women, 45% men) over 60 years old, 21.3% meet criteria for JHS. These subjects scored significantly higher in both State (F = 5.53; p = 0.02) and Trait (F = 4.68; p = 0.03) anxiety and the GHQ 28 (F = 6.29; p = 0.01). Compared with non JHS subjects, they had more AD (34.8% vs. 11.8%; x² = 6.90; p = 0.02) and mood disorders (30.4% vs. 10.6%; x² = 5.65; p = 0.041) in the past year prevalence. A multiple logistic regression analysis showed that both JHS (β = 0.196; p = 0.04) and fears (β = 0.34; p = 0.001) are predictors of AD (r² = 188; p = 0.001) in this population.

Conclusions

Joint hypermobility syndrome is associated with anxiety in the elderly population, and it may be used as a physical marker for AD among subjects within this age range. Copyright © 2017 John Wiley & Sons, Ltd.     

Association between oxidized low‐density lipoprotein and cognitive impairment in patients with ischemic stroke

Background and purpose

The association between oxidized low‐density lipoprotein (oxLDL) and cognitive impairment is unclear. This study aimed to investigate the potential association between oxLDL and cognitive impairment among patients with acute ischemic stroke.

Methods

We measured the levels of oxLDL and recorded the Mini‐Mental State Examination (MMSE) score in patients with acute ischemic stroke who were recruited from the Study of Oxidative Stress in Patients with Acute Ischemic Stroke. Cognitive impairment was defined as an MMSE score of <24. The association between oxLDL and cognitive impairment was assessed by multivariate logistic or linear regression analysis. Other clinical variables of interest were also studied.

Results

A total of 3726 patients [1287 (34.54%) female] were included in this study, with a mean age of 63.62 ± 11.96 years. After adjusting for potential confounders in our logistic regression model, each SD increase in oxLDL was associated with a 26% increase in the prevalence of cognitive impairment (odds radio, 1.26; 95% confidence interval, 1.13–1.39; P < 0.0001). Similarly, higher oxLDL was associated with lower MMSE scores, with a 0.56‐point decrease in MMSE score for every SD increase in oxLDL in a linear regression analysis (β = ?0.56; 95% confidence interval, ?0.81 to ?0.32; P < 0.0001). There were no significant interactions between oxLDL and age, sex or education levels for cognitive impairment (all interactions, P > 0.05).

Conclusions

Elevated levels of oxLDL were associated with a higher prevalence of cognitive impairment in patients with ischemic stroke.     

Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis

Background

Gastrointestinal complications are common in hereditary transthyretin amyloid (ATTRm) amyloidosis. The underlying mechanisms have not been fully elucidated, and the patients’ small bowel function remains largely unexplored. The aim of the present study was to compare the small bowel motility in ATTRm amyloidosis patients with that in non‐amyloidosis patient controls.

Methods

ATTRm amyloidosis patients undergoing evaluation for liver transplantation were consecutively investigated with 24‐hour duodenojejunal manometry (n = 19). The somatostatin analogue octreotide was used to induce fasting motility. Patients with age at onset of ≥50 years were defined as late‐onset cases. For each patient, three age‐ and sex‐matched patient controls (n = 57) were selected from the total pool of investigated patients.

Key Results

Manometry was judged as abnormal in 58% of the patients and in 26% of the patient controls (P = .01). Patients displayed significantly more daytime phase III migrating motor complexes than patient controls (median 4 vs 2, P < .01), and had a higher frequency of low‐amplitude complexes (16% vs 4%; however, this difference did not reach statistical significance, P = .10). Furthermore, late‐onset patients showed a delay in octreotide response (5.4 vs 3.8 minutes, P < .01), but this was not observed for early‐onset patients or within the control group.

Conclusions and Inferences

Patients with ATTRm amyloidosis displayed abnormalities in their small bowel motility more frequently than non‐amyloidosis patient controls, and the manometric pattern was probably best consistent with a combined neuromyopathic disorder. The delayed octreotide response in late‐onset patients warrants further investigation.     

Efficacy and safety of olorinab,a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: Results from a phase 2b randomized placebo-controlled trial (CAPTIVATE)

Background

Olorinab is a highly selective, peripherally acting, full agonist of cannabinoid receptor 2. This study assessed the efficacy and safety of olorinab to treat abdominal pain in patients with irritable bowel syndrome with diarrhea (IBS-D) and constipation (IBS-C).

Methods

CAPTIVATE was a phase 2b, randomized, double-blind, placebo-controlled, parallel-group trial. Eligible participants aged 18–70 years with IBS-C and IBS-D diagnosed per Rome IV received olorinab 10 mg, 25 mg, or 50 mg three times daily (TID) or placebo TID for 12 weeks. The primary endpoint was the change in patient-reported average abdominal pain score (AAPS) from baseline to Week 12.

Key Results

A total of 273 participants were randomized to receive olorinab 10 mg (n = 67), olorinab 25 mg (n = 67), olorinab 50 mg (n = 69), or placebo (n = 70). Although a treatment response was observed across all groups, the weekly change in average AAPS from baseline to Week 12 was not significantly different between placebo and any olorinab dose. In a prespecified subgroup analysis of participants with a baseline AAPS ≥6.5, olorinab 50 mg (n = 35) significantly improved AAPS compared with placebo (n = 30) (p = 0.014). Adverse event rates were comparable between olorinab and placebo and there were no reported serious adverse events or deaths.

Conclusion and Inferences

Although olorinab was well-tolerated and improved weekly AAPS, the primary endpoint was not met. However, in participants with moderate-to-severe pain at baseline (AAPS ≥6.5), olorinab 50 mg significantly improved weekly AAPS compared with placebo. ClinicalTrials.gov : NCT04043455.     

Aspiration versus stent retriever for posterior circulation stroke: A meta-analysis

Aims

New thrombectomy strategies have emerged recently. Differences between posterior circulation stroke management via aspiration and stent retriever remain to be evaluated. We compared the safety and efficacy of aspiration and stent retriever in treating posterior circulation stroke.

Methods

Three databases (PubMed, Embase, and Cochrane Library) were systematically searched for studies comparing aspiration and stent retriever in patients with posterior circulation stroke. The modified Newcastle-Ottawa scale was used to assess the risk of bias. A random-effects model was used.

Results

Fifteen cohort studies with 1451 patients were included. Pooled results showed a significant difference in total complication (odds ratio [OR] 0.48, 95% confidence interval [CI] [0.30, 0.76], p = 0.002). successful recanalization (1.85, [1.30, 2.64], p = 0.0006), favorable outcome (1.30, [1.02, 1.67], p = 0.04), procedure duration (−22.10, [−43.32, −0.88], p = 0.04), complete recanalization (4.96, [1.06, 23.16], p = 0.009), and first-pass effect (2.59, [1.55, 4.32], p = 0.0003) between the aspiration and stent retriever groups, and in favor of aspiration. There was no significant difference in the outcomes of rescue therapy (1.42, [0.66, 3.05], p = 0.37) between the two groups.

Conclusion

Patients with posterior circulation stroke receiving treatment with aspiration achieved better recanalization, first-pass effect, and shorter procedure time. Aspiration may be more secure than a stent retriever.     

Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized,double‐blind,placebo‐controlled study

Background

Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS‐C) was needed.

Methods

This was a randomized, double‐blind, placebo‐controlled, dose‐finding trial. Japanese patients with IBS‐C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12‐week treatment period. The primary endpoint was responder rate of global assessment of relief of IBS symptoms during 12 weeks. The secondary endpoints included responder rates of complete spontaneous bowel movement (CSBM), SBM and abdominal pain/discomfort relief and others.

Key Results

The primary endpoint was 23.2%, 36.2%, 38.7%, 34.8%, and 38.3% in placebo (n = 112), 0.0625 (n = 116), 0.125 (n = 111), 0.25 (n = 112), and 0.5 (n = 107) mg of linaclotide groups with the difference from the placebo group in each linaclotide group (13.0%, 15.5%, 11.6%, 15.1%, P > .05). Monthly responder rate of global assessment of relief of IBS symptoms at month 3 (48.6%), responder rate of CSBM during 12 weeks (45.8%), and responder rate of abdominal pain/discomfort relief during 12 weeks (32.7%) in the 0.5 mg were significantly higher than those in placebo group (29.5%, P < .01; 25.9%, P < .01; and 18.8%, P < .05 respectively). The most frequent adverse event in the linaclotide groups was diarrhea.

Conclusions & Inferences

This study suggests that a linaclotide dose of 0.5 mg may be appropriate in Japanese patients with IBS‐C.     

Recent substance use among clients with early psychosis and the potential to graduate from New Journeys

Aim

This study examined the relationship between recent substance use prior to intake and program graduation among young adults with early psychosis enrolled in coordinated specialty care.

Methods

Participants (N = 248) were from New Journeys, a network of coordinated specialty care programs in Washington State. Recent (i.e., past 30 days) alcohol, cannabis, and other substance use was collected at intake and process data (e.g., contact) was collected by clinicians across a 2-year period.

Results

At intake, 32% of participants reported alcohol use only, 26% cannabis use only, and 15% both alcohol and cannabis use. Participants who reported alcohol use only (p = .02), cannabis use only (p = .03), and any substance use (p = .02) had significantly lower chances of graduating from coordinated specialty care than individuals who do not use substances.

Conclusions

Unlike prior work, recent substance use influences clients' potential to graduate from New Journeys. Additional focus on the implementation of substance use treatment, with an emphasis on alcohol use, in coordinated specialty care programs is needed improve program completion rates.