Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about ...risks related to tapering, including overdose and mental health crisis.
To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids.
Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion.
Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period.
Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity.
The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years 95% CI, 3.0-4.6; aIRR, 1.68 95% CI, 1.53-1.85). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years 95% CI, 3.2-5.3; aIRR, 2.28 95% CI, 1.96-2.65). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21).
Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.
Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome. The severity of these ...symptoms has been correlated with the degree of GI microbial dysbiosis. The study objective was to assess tolerability of a probiotic (Bifidobacterium infantis) in combination with a bovine colostrum product (BCP) as a source of prebiotic oligosaccharides and to evaluate GI, microbiome and immune factors in children with ASD and GI co-morbidities. This pilot study is a randomized, double blind, controlled trial of combination treatment (BCP + B. infantis) vs. BCP alone in a cross-over study in children ages 2-11 with ASD and GI co-morbidities (n = 8). This 12-week study included 5 weeks of probiotic-prebiotic supplementation, followed by a two-week washout period, and 5 weeks of prebiotic only supplementation. The primary outcome of tolerability was assessed using validated questionnaires of GI function and atypical behaviors, along with side effects. Results suggest that the combination treatment is well-tolerated in this cohort. The most common side effect was mild gassiness. Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors. Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants. Although limited conclusions can be drawn from this small pilot study, the results support the need for further research into the efficacy of these treatments.
There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of ...our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group ( p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.
Postnatal growth restriction is common in preterm infants and is associated with long-term neurodevelopmental impairment. Recent trends in postnatal growth restriction are unclear.
Birth and ...discharge weights from 25,899 Californian very low birthweight infants (birth weight 500-1500 g, gestational age 22-32 weeks) who were born between 2005 and 2012 were converted to age-specific Z-scores and analysed using multivariable modelling.
Birthweight Z-score did not change between 2005 and 2012. However, the adjusted discharge weight Z-score increased significantly by 0.168 Z-scores (0.154, 0.182) over the study period, and the adjusted fall in weight Z-score between birth and discharge decreased significantly between those dates (by 0.016 Z-scores/year). The proportion of infants who were discharged home below the 10th weight-for-age centile or had a fall in weight Z-score between birth and discharge of >1 decreased significantly over time. The comorbidities most associated with poorer postnatal growth were medical or surgical necrotising enterocolitis, isolated gastrointestinal perforation and severe retinopathy of prematurity, which were associated with an adjusted mean reduction in discharge weight Z-score of 0.24, 0.57, 0.46 and 0.32, respectively. Chronic lung disease was not a risk factor after accounting for length of stay.
Postnatal, but not prenatal, growth improved among very low birthweight infants between 2005 and 2012. Neonatal morbidities including necrotising enterocolitis, gastrointestinal perforations and severe retinopathy of prematurity have significant negative effects on postnatal growth.
Gestational exposure to several common agricultural pesticides can induce developmental neurotoxicity in humans, and has been associated with developmental delay and autism.
We evaluated whether ...residential proximity to agricultural pesticides during pregnancy is associated with autism spectrum disorders (ASD) or developmental delay (DD) in the Childhood Autism Risks from Genetics and Environment (CHARGE) study.
The CHARGE study is a population-based case-control study of ASD, DD, and typical development. For 970 participants, commercial pesticide application data from the California Pesticide Use Report (1997-2008) were linked to the addresses during pregnancy. Pounds of active ingredient applied for organophophates, organochlorines, pyrethroids, and carbamates were aggregated within 1.25-km, 1.5-km, and 1.75-km buffer distances from the home. Multinomial logistic regression was used to estimate the odds ratio (OR) of exposure comparing confirmed cases of ASD (n = 486) or DD (n = 168) with typically developing referents (n = 316).
Approximately one-third of CHARGE study mothers lived, during pregnancy, within 1.5 km (just under 1 mile) of an agricultural pesticide application. Proximity to organophosphates at some point during gestation was associated with a 60% increased risk for ASD, higher for third-trimester exposures (OR = 2.0; 95% CI: 1.1, 3.6), and second-trimester chlorpyrifos applications (OR = 3.3; 95% CI: 1.5, 7.4). Children of mothers residing near pyrethroid insecticide applications just before conception or during third trimester were at greater risk for both ASD and DD, with ORs ranging from 1.7 to 2.3. Risk for DD was increased in those near carbamate applications, but no specific vulnerable period was identified.
This study of ASD strengthens the evidence linking neurodevelopmental disorders with gestational pesticide exposures, particularly organophosphates, and provides novel results of ASD and DD associations with, respectively, pyrethroids and carbamates.
Periconceptional folate is essential for proper neurodevelopment.
Maternal folic acid intake was examined in relation to the risk of autism spectrum disorder (ASD) and developmental delay (DD).
...Families enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n = 429), DD (n = 130), or typical development (TD; n = 278) confirmed at the University of California Davis Medical Investigation of Neurodevelopmental Disorders Institute by using standardized clinical assessments. Average daily folic acid was quantified for each mother on the basis of dose, brands, and intake frequency of vitamins, supplements, and breakfast cereals reported through structured telephone interviews.
Mean (±SEM) folic acid intake was significantly greater for mothers of TD children than for mothers of children with ASD in the first month of pregnancy (P1; 779.0 ± 36.1 and 655.0 ± 28.7 μg, respectively; P < 0.01). A mean daily folic acid intake of ≥600 μg (compared with <600 μg) during P1 was associated with reduced ASD risk (adjusted OR: 0.62; 95% CI: 0.42, 0.92; P = 0.02), and risk estimates decreased with increased folic acid (P-trend = 0.001). The association between folic acid and reduced ASD risk was strongest for mothers and children with MTHFR 677 C>T variant genotypes. A trend toward an association between lower maternal folic acid intake during the 3 mo before pregnancy and DD was observed, but not after adjustment for confounders.
Periconceptional folic acid may reduce ASD risk in those with inefficient folate metabolism. The replication of these findings and investigations of mechanisms involved are warranted.
The collective findings from human microbiome research, randomized controlled trials on specific microbes (i.e., probiotics), and associative studies of fermented dairy consumption provide evidence ...for the beneficial effects of the regular consumption of safe live microbes. To test the hypothesis that the inclusion of safe, live microbes in the diet supports and improves health, we propose assessment of the types and evidentiary quality of the data available on microbe intake, including the assembly and evaluation of evidence available from dietary databases. Such an analysis would help to identify gaps in the evidence needed to test this hypothesis, which can then be used to formulate and direct initiatives focused on prospective and randomized controlled trials on live microbe consumption. Outcomes will establish whether or not the evidence exists, or can be generated, to support the establishment of dietary recommendations for live microbes.
Food insecurity, limited access to adequate food, in adulthood is associated with poor health outcomes that suggest a pattern of accelerated aging. However, little is known about factors that impact ...food insecurity in midlife which in turn could help to identify potential pathways of accelerated aging. Low-income adults (n = 17,866; 2014 National Health Interview Survey), ages 18 to 84, completed a 10-item food security module and answered questions regarding health challenges (chronic conditions and functional limitations) and financial worry. We used multinomial logistic regression for complex samples to assess the association of health challenges and financial worry with food insecurity status and determine whether these associations differed by age group, while adjusting for poverty, sex, race/ethnicity, education, family structure, social security, and food assistance. Food insecurity rates were highest in late- (37.5%) and early- (36.0%) midlife, relative to younger (33.7%) and older (20.2%) age groups and, furthermore, age moderated the relationship between food insecurity and both risk factors (interaction p-values < .05, for both). The effects of poor health were stronger in midlife relative to younger and older ages. Unlike younger and older adults, however, adults in midlife showed high levels of food insecurity regardless of financial worry.
Abstract Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine ...production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. Methods We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains. Results Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio OR = 1.40, 95% confidence interval CI, 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = −3.63, SE = 1.33, p = .04). Conclusions This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.
Identifying groups at increased risk for political violence can support prevention efforts. We determine whether "Make America Great Again" (MAGA) Republicans, as defined, are potentially such a ...group.
Nationwide survey conducted May 13-June 2, 2022 of adult members of the Ipsos KnowledgePanel. MAGA Republicans are defined as Republicans who voted for Donald Trump in the 2020 presidential election and deny the results of that election. Principal outcomes are weighted proportions of respondents who endorse political violence, are willing to engage in it, and consider it likely to occur.
The analytic sample (n = 7,255) included 1,128 (15.0%) MAGA Republicans, 640 (8.3%) strong Republicans, 1,571 (21.3%) other Republicans, and 3,916 (55.3%) non-Republicans. MAGA Republicans were substantially more likely than others to agree strongly/very strongly that "in the next few years, there will be civil war in the United States" (MAGA Republicans, 30.3%, 95% CI 27.2%, 33.4%; strong Republicans, 7.5%, 95% CI 5.1%, 9.9%; other Republicans, 10.8%, 95% CI 9.0%, 12.6%; non-Republicans, 11.2%, 95% CI 10.0%, 12.3%; p < 0.001) and to consider violence usually/always justified to advance at least 1 of 17 specific political objectives (MAGA Republicans, 58.2%, 95% CI 55.0%, 61.4%; strong Republicans, 38.3%, 95% CI 34.2%, 42.4%; other Republicans, 31.5%, 95% CI 28.9%, 34.0%; non-Republicans, 25.1%, 95% CI 23.6%, 26.7%; p < 0.001). They were not more willing to engage personally in political violence.
MAGA Republicans, as defined, are more likely than others to endorse political violence. They are not more willing to engage in such violence themselves; their endorsement may increase the risk that it will occur.
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