Use of olanzapine compared with clozapine for treatment-resistant schizophrenia in a real-world setting: nationwide register-based study

Background Clozapine is generally considered as the treatment of choice for patients with treatment-resistant schizophrenia (TRS). However, its superiority has recently been questioned because olanzapine has been suggested as non-inferior to clozapine in its effectiveness. Aims We aimed to investigate the current status of clozapine prescriptions to identify any disparity between clinical guidelines and real-world practices. Method In this study, we utilised the Health Insurance Review Agency database in the Republic of Korea to investigate the real-world effectiveness of clozapine for patients with TRS. We compared differences in patient variables before and after clozapine administration, and we also performed survival analyses for both psychiatric admissions and emergency room visits among patients who used clozapine or olanzapine. Results This study investigated an incident cohort of 64 442 patients, and 2338 patients have been prescribed clozapine. Of these, 998 patients had TRS. In survival analysis, clozapine showed a worse survival rate for psychiatric admissions than olanzapine (hazard ratio 0.615). We also identified that clinicians tended to try a number of antipsychotics, as recommended, before starting patients on clozapine. Conclusions In conclusion, we found that olanzapine led to higher survival rates for psychiatric admissions than clozapine. Thus, considering the risk of serious adverse effects, clozapine may be used conservatively. Considering several studies advocating superior efficacy of clozapine, further studies with extensive data are recommended.

Care consumption of people with multiple sclerosis: A multichannel sequence analysis in a population-based setting in British Columbia, Canada

Background: Persons with multiple sclerosis (PwMS) typically require complex multidisciplinary care, which is rarely formally assessed. Objectives: We applied multichannel sequence analysis (MCSA) to identify care consumption patterns by PwMS in British Columbia, Canada. Methods: We created two cohorts, comprising incident and prevalent MS cases, using linked clinical and administrative data. We applied MCSA to quantify and compare the care pathways of PwMS, based on all-cause hospitalizations and physician visits (divided into five specialities). Care consumption clusters were characterized using demographic and clinical features. Results: From 1048 incident and 3180 prevalent PwMS, the MCSA identified 12 and 6 distinct care consumption clusters over a median follow-up of 9.6 and 13.0 years, respectively. Large disparities between clusters were observed; the median number of annual consultations ranged from 5.6 to 21.3 for general practitioners, 1.2 to 4.6 for neurologists and 0 to 5.3 for psychiatrists in the incident cohort. Characteristics at MS symptom onset associated with the highest care consumption included high comorbidity burden and older age. There were similar disparities and associations for prevalent PwMS. Conclusion: The distinct patterns of care consumption, which were reminiscent of the heterogeneity of MS itself, may facilitate health service planning and evaluation, and provide a novel outcome measure in health research.

354 Trends in the Drug-Sparing Effects for Benzodiazepines and Prescription Opioids among Insomnia Patients on Suvorexant in the US

Introduction Use of benzodiazepines to treat insomnia has been associated with serious side effects and abuse potential. Insomnia patients are at high risk of opioid abuse and better sleep patterns may help to reduce opioid use. This study examined the trend in the use of benzodiazepines and prescription opioids before and after initiation of suvorexant in insomnia patients. Methods The study analyzed 2015–2019, Optum Clinformatics Data Mart. Insomnia patients, identified using ICD-9/10 codes and prescribed suvorexant were included. The study included incident (newly diagnosed) and prevalent cohorts of insomnia patients. The proportion of patients on benzodiazepines or prescription opioids were calculated for 12 monthly intervals before (pre-period) and after initiation of suvorexant (post-period). Interrupted time series (ITS) analysis was conducted to assess trends for use of benzodiazepine or prescription opioids over time. Results A total of 5,939 patients from the incident insomnia cohort and 18,920 from the prevalent cohort were included. For the incident cohort, mean age was 64.47 (SD: 15.48), 63% were females, 71% had Medicare Advantage coverage, 59% had Charlson comorbidity index score (CCI) ≥ 1, 27% had an anxiety disorder and 16% had substance abuse disorder. Prevalent insomnia cohort was similar but had higher CCI. Results from ITS suggested that at the beginning of the pre-period, 28% of incident insomnia patients used either opioids or benzodiazepines with the rate of use in the pre-period increasing by 0.11% per month. In the post-period, the rate of use decreased by 0.33% per month. About 26% patients used benzodiazepines or opioids at 12-month after suvorexant initiation. In the absence of suvorexant, this proportion would have been 31%. Similar findings were observed for the prevalent insomnia cohort. A larger decrease was observed for opioid use than benzodiazepines. Conclusion The rate of benzodiazepines or prescription opioid use decreased over time after the initiation of suvorexant. Suvorexant has the potential to reduce the use of opioids and benzodiazepines among insomnia patients. Further research is needed to confirm these findings. Support (if any) This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Higher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections

Plasmodium falciparum gametocyte kinetics and infectivity may differ between chronic and incident infections. In the current study, we assess parasite kinetics and infectivity to mosquitoes among children (aged 5–10 years) from Burkina Faso with (a) incident infections following parasite clearance (n = 48) and (b) chronic asymptomatic infections (n = 60). In the incident infection cohort, 92% (44/48) of children develop symptoms within 35 days, compared to 23% (14/60) in the chronic cohort. All individuals with chronic infection carried gametocytes or developed them during follow-up, whereas only 35% (17/48) in the incident cohort produce gametocytes before becoming symptomatic and receiving treatment. Parasite multiplication rate (PMR) and the relative abundance of ap2-g and gexp-5 transcripts are positively associated with gametocyte production. Antibody responses are higher and PMR lower in chronic infections. The presence of symptoms and sexual stage immune responses are associated with reductions in gametocyte infectivity to mosquitoes. We observe that most incident infections require treatment before the density of mature gametocytes is sufficient to infect mosquitoes. In contrast, chronic, asymptomatic infections represent a significant source of mosquito infections. Our observations support the notion that malaria transmission reduction may be expedited by enhanced case management, involving both symptom-screening and infection detection.

Early-Onset Parkinsonism and Early-Onset Parkinson’s Disease: A Population-Based Study (2010-2015)

Background: Early-onset Parkinson’s disease (EOPD), occurring between ages 40 and 55, carries social, societal, and personal consequences and may progress, with fewer comorbidities than typical, later-onset disease. Objective: To examine the incidence and survival of EOPD and other Parkinsonism occurring before age 55 in the population-based cohort of residents in seven Minnesota counties. Methods: A movement-disorder specialist reviewed all the medical records in a 2010–2015 Parkinsonism-incident cohort to confirm diagnosis and subtypes. Results: We identified 27 patients diagnosed at < 50 years with incident Parkinsonism 2010–15:11 (41%) cases of EOPD, 13 (48%) drug-induced Parkinsonism, and 3 (11%) other Parkinsonism and 69 incident cases of Parkinsonism < 55 years of age. Overall incidence for Parkinsonism < 50 years was 1.98/100,000 person-years, and for EOPD was 0.81/100,000 person-years. In patients < 55 years, Parkinsonism incidence was 5.05/100,000 person-years: in EOPD, 2.05/100,000 person-years. Levodopa-induced dyskinesia was present in 45%of EOPD (both < 50 years and < 55 years). Onset of cardinal motor symptoms was proximate to the diagnosis of EOPD, except for impaired postural reflexes, which occurred later in the course of EOPD. Among the 69 Parkinsonism cases < 55 years, 9 (13%; all male) were deceased (only 1 case of EOPD). Men had a higher mortality risk compared to women (p = 0.049). Conclusion: The incidence of EOPD < 50 years was 0.81/100,000 person-years (1.98 in Parkinsonism all type); prior to 55 years was 2.05/100,000 person-years (5.05 in Parkinsonism all type) with higher incidence in men than women. Men with Parkinsonism, all type, had higher mortality compared to women.

The effect of smoking on cumulative damage in systemic lupus erythematosus: An incident cohort study

Objectives To investigate the relationship between smoking history and pack-year exposure on the rate of end-organ damage in systemic lupus erythematosus (SLE). Methods The SLE incident cohort included patients who met American College of Rheumatology (ACR) 1997 or SLE International Collaborating Clinics (SLICC) 2012 SLE criteria and had rheumatology encounters at a US academic institution (2008–16). The primary outcome was median time to SLICC/ACR damage index (SLICC/ACR-DI) increase or death. Main explanatory variables were smoking status and pack-years. Covariates included age, sex, race, ethnicity, receipt of Medicaid, neighborhood area deprivation index, and baseline SLE damage. Damage increase-free survival was evaluated by smoking status and pack-years using Kaplan-Meier and Cox proportional hazards methods. Results Patients of Black race and Medicaid recipients were more commonly current smokers ( p’s < 0.05). Former smokers were older and more likely to have late-onset SLE (54% versus 33% of never and 29% of current smokers, p = 0.001). Median time to SLICC/ACR-DI increase or death was earlier in current or former compared to never smokers (4.5 and 3.4 versus 9.0 yrs; p = 0.002). In multivariable models, the rate of damage accumulation was twice as fast in current smokers (HR 2.18; 1.33, 3.57) and smokers with a >10 pack-year history (HR 2.35; 1.15, 3.64) versus never smokers. Conclusions In this incident SLE cohort, past or current smoking predicted new SLE damage 4-5 years earlier. After adjustment, current smokers and patients with a pack-year history of >10 years accumulated damage at twice the rate of never smokers.

Toxoplasma gondii and multiple sclerosis: a population-based case–control study

According to the hygiene hypothesis, parasites could have a protective role in the development of Multiple Sclerosis (MS). Our aim was to assess the association between presence of anti-Toxoplasma gondii antibodies and MS. MS patients were randomly selected from a population-based incident cohort of MS patients in the city of Catania. Age and sex-matched controls were randomly selected from the general population. Clinical and sociodemographic variables were recorded with a structured questionnaire and a blood sample was taken for serological analysis. Specific T. gondii IgG have been detected with a commercial kit. Adjusted Odds Ratios (ORs) were estimated using unconditional logistic regression. 129 MS subjects (66.7% women with a mean age 44.7 ± 11.0 years) and 287 controls (67.3% women with a mean age 48.1 ± 15.6 years) have been enrolled in the study. Anti-T. gondii antibodies were found in 38 cases (29.5%) and 130 controls (45.4%) giving an adjusted OR of 0.56 (95%CI 0.34–0.93). History of mononucleosis and high educational level were significantly associated with MS (adjOR 2.22 and 1.70 respectively) while an inverse association was found between high educational level and T. gondii seropositivity (adjOR 0.42). Our results further support the protective role of parasitic infections in MS.