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Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues. We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score-matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan-Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control. Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

The evidence base for the association between montelukast and adverse neuropsychiatric outcomes is mixed and inconclusive. Several methodological limitations have been identified in the evidence base on the safety of montelukast in observational studies. To investigate the association between new montelukast exposure and 1-year incident neuropsychiatric diagnoses with improved precision and control for baseline confounders. This propensity score-matched cohort study was conducted using electronic health records from 2015 to 2019 in the TriNetX Analytics Network patient repository of more than 51 million patients from 56 health care organizations, mainly in the US. Included patients were those aged 15 to 64 years at index prescription for montelukast or for control prescription who had a history of asthma or allergic rhinitis. After propensity score matching for various baseline confounders, including comorbidities and dispensed prescription medicines, we included 154 946 patients, of whom 77 473 individuals were exposed to montelukast. Patients were followed up for 12 months. Data were analyzed from June through November 2021. New dispensed prescription for leukotriene receptor antagonist montelukast or control medication. Incident neuropsychiatric diagnoses at 12 months identified using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. There were 72 490 patients with asthma (44 726 [61.7%] women; mean [SD] age at index prescription, 35 [15] years) and 82 456 patients with allergic rhinitis (54 172 [65.7%] women; mean [SD] age at index prescription, 40 [14] years). In patients exposed to montelukast, the odds ratio [OR] for any incident neuropsychiatric outcome was 1.11 (95% CI, 1.04-1.19) in patients with asthma and 1.07 (95% CI, 1.01-1.14) in patients with allergic rhinitis compared with patients who were unexposed. The highest OR was for anxiety disorders (OR, 1.21; 95% CI, 1.05-1.20) among patients with asthma exposed to montelukast and insomnia (OR, 1.15; 95% CI, 1.05-1.27) among patients with allergic rhinitis exposed to montelukast. This study found that patients with asthma or allergic rhinitis had increased odds of adverse neuropsychiatric outcomes after montelukast initiation. These findings suggest that clinicians should consider monitoring potential adverse mental health symptoms during montelukast treatment, particularly in individuals with a history of mental health or sleep problems.

The major anti-hypertensive (AHT) drug classes have been associated with differential risks of psychiatric disorders. However, existing data are limited largely to depression, and confounding variables have not always been controlled for. We sought to fill the evidence gap, using TriNetX Analytics, an electronic health records network. Amongst 58.6 million patients aged 18–90 years, patients prescribed a calcium channel blocker (CCB) were compared with those taking a diuretic, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or β-blocker. Cohorts were propensity score-matched for age, sex, race, and blood pressure. Over a 2-year exposure period, we measured the incidence and risk ratio of a first diagnosis (ICD-10 codes), or a recurrence, of psychotic, affective, and anxiety disorders, as well as substance use disorders and sleep disorders. Cohort sizes ranged from 33,734 to 322,814. CCBs were associated with a lower incidence of psychotic, affective, and anxiety disorders than β-blockers (risk ratios 0.69–0.99) and a higher incidence than ARBs (risk ratios 1.04–2.23) for both first and recurrent diagnoses. Comparisons of CCBs with ACEIs or diuretics showed smaller risk ratios that varied between disorders, and between first episode and recurrence. AHT classes were also associated with the incidence of substance use and sleep disorders. Results remained largely unchanged after more extensive cohort matching for additional potential confounders. In a secondary analysis, a comparison between ARBs and ACEIs showed lower rates of psychotic, affective, and substance use disorders with ARBs, but higher risks of anxiety and sleep disorders. In conclusion, AHT classes are differentially associated with the incidence of psychiatric disorders. ARBs show the most advantageous profile and β-blockers the least. The apparent beneficial effects of ARBs merit further study.

BackgroundThe evidence base on montelukast-associated adverse outcomes is inconclusive in children and young persons (CYP) with asthma. We aimed to investigate 1-year incidence of neuropsychiatric diagnoses after initiation of montelukast as an adjunct therapy to inhaled corticosteroids (ICSs) in CYP aged 3–17 years with asthma.MethodsThis propensity score matched cohort study was conducted using electronic health records between 2015 and 2019 in the TriNetX Analytics Network patient repository in the USA. Neuropsychiatric diagnoses were identified using the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. We estimated risk ratios (RRs), absolute risk increase (ARI) and number needed to harm (NNH) with 95% CIs.FindingsThe mean age (SD) at index prescription in the 107 384 CYP with asthma was 8.7 (4.0) years (93 461 (87%) mild to moderate asthma; 62 301 (58%) male; 53 485 (50%) white; 33 107 (31%) black/African American). Montelukast was associated with excess incidence of any neuropsychiatric outcome (71 per 1000 persons with montelukast and 54 per 1000 persons with no montelukast; RR 1.32 (95% CI 1.25 to 1.39); ARI per 100 persons, 1.71 (95% CI 1.44 to 1.98); 1-year NNH, 58 patients (95% CI 51 to 69)). The highest excess risk in the montelukast group was for sleep disorders (RR 1.63 (95% CI 1.50 to 1.77); ARI per 100 persons 1.17 (95% CI 1.00 to 1.33); NNH, 85 patients (95% CI 75 to 100)). Montelukast use was also associated with excess incidence of anxiety disorders (RR 1.16 (95% CI 1.08 to 1.24)) and mood disorders (RR 1.16 (95% CI 1.05 to 1.29)).ConclusionsIn CYP with asthma who were treated with ICSs, adjunct treatment with montelukast was associated with a higher incidence of neuropsychiatric outcomes compared with those who were not exposed to montelukast.

Antihypertensive drugs (AHTs) are associated with lowered risks of neurodegenerative diseases and stroke. However, the relative risks associated with different AHT classes are unclear. Using an electronic health record network with 34 million eligible patients, we compared rates of these disorders over a 2-year period, in propensity score-matched cohorts of people taking calcium channel blockers (CCBs) compared with those taking other AHT classes. CCBs were associated with a higher incidence of all disorders compared with renin-angiotensin system agents, and a higher incidence of dementia and cerebrovascular disease compared with diuretics. CCBs were associated with a lower incidence of movement disorders and cerebrovascular disease compared with beta-blockers. The data show that AHT classes confer differential risks of neurodegenerative and cerebrovascular diagnoses.

There are concerns that eating disorders have become commoner during the coronavirus disease 2019 (COVID-19) pandemic. Using the electronic health records of 5.2 million people aged under 30, mostly in the USA, we show that the diagnostic incidence was 15.3% higher in 2020 overall compared with previous years (relative risk 1.15, 95% CI 1.12−1.19). The relative risk increased steadily from March 2020 onwards, exceeding 1.5 by the end of the year. The increase occurred solely in females, and primarily related to teenagers and anorexia nervosa. A higher proportion of patients with eating disorders in 2020 had suicidal ideation (hazard ratio HR = 1.30, 1.16−1.47) or attempted suicide (HR = 1.69, 1.21−2.35).

Antihypertensive drugs (AHTs) are associated with lowered risks of neurodegenerative diseases and stroke. However, the relative risks associated with different AHT classes are unclear. Using an electronic health records network, we compared rates of these disorders over a 2 year period in propensity score matched cohorts of people taking calcium channel blockers (CCBs) compared to those taking other AHT classes. CCBs were associated with a higher incidence of all disorders compared to renin-angiotensin system agents, and a higher incidence of dementia and cerebrovascular disease compared to diuretics. CCBs were associated with a lower incidence of movement disorders and cerebrovascular disease than with β-blockers. The data show that AHT classes confer differential risks of neurodegenerative and cerebrovascular diagnoses.

Air assistance and electrical charge transfer to droplets can optimize pesticide applications and reduce losses in sweet pepper cultivation. The objective of this study was to evaluate the effects of spray rate and pneumatic spraying with and without an electrostatic charge on spray deposition, spray coverage, and ground losses in sweet pepper crops. Four application techniques were employed: standard farmer hydraulics (SFH), reduced volume hydraulics (RVH), pneumatic with air and electrostatic assistance (PAEA), and pneumatic with air assistance (PAA). The effects of the application techniques on spray deposition varied as a function of plant height, canopy depth, and leaf surface. The SFH resulted in the greatest amounts of spray deposition on the adaxial leaf surface. In contrast, PAEA resulted in the greatest amounts of deposition on the abaxial leaves. The PAEA treatment improved spray coverage on abaxial leaves of the external canopy but did not improve spray coverage on the internal canopy. Compared to the SFH treatment, the 50% reduction in the spray rate of the RVH treatment decreased deposition and spray coverage. The pneumatic treatments, regardless of electrostatic charges, resulted in lower spray loss to the ground.

Laurie Ozelius and colleagues identify mutations in GNAL in families with primary torsion dystonia, a movement disorder characterized by repetitive twisting muscle contractions and postures. GNAL encodes Gα olf , a stimulatory G protein α subunit. Dystonia is a movement disorder characterized by repetitive twisting muscle contractions and postures 1 , 2 . Its molecular pathophysiology is poorly understood, in part owing to limited knowledge of the genetic basis of the disorder. Only three genes for primary torsion dystonia (PTD), TOR1A (DYT1) 3 , THAP1 (DYT6) 4 and CIZ1 (ref. 5 ), have been identified. Using exome sequencing in two families with PTD, we identified a new causative gene, GNAL , with a nonsense mutation encoding p.Ser293* resulting in a premature stop codon in one family and a missense mutation encoding p.Val137Met in the other. Screening of GNAL in 39 families with PTD identified 6 additional new mutations in this gene. Impaired function of several of the mutants was shown by bioluminescence resonance energy transfer (BRET) assays.

A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2–59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18–59 years, 7–17 years, and 2–6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2–5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2–4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4–73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.