Nevin Manimala

JAMA Psychiatry. 2023 Sep 6. doi: 10.1001/jamapsychiatry.2023.3220. Online ahead of print.

ABSTRACT

IMPORTANCE: People with psychosis are more likely to be born and live in densely populated and socioeconomically deprived environments, but it is unclear whether these associations are a cause or consequence of disorder.

OBJECTIVE: To investigate whether trajectories of exposure to deprivation and population density before and after diagnosis are associated with psychotic disorders or nonpsychotic bipolar disorder.

DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study included all individuals born in Sweden between January 1, 1982, and December 31, 2001, diagnosed for the first time with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychotic disorder or nonpsychotic bipolar disorder between their 15th birthday and cohort exit (December 31, 2016). One sex- and birth year-matched control participant per case was selected. Data analysis was performed from July 2021 to June 2023.

EXPOSURES: The main exposures were quintiles of neighborhood-level deprivation and population density each year from birth to age 14 years and from first diagnosis until cohort exit.

MAIN OUTCOMES AND MEASURES: The main outcomes were the odds of a serious mental illness outcome associated with trajectories of deprivation and population density, before and after diagnosis in cases. Group-based trajectory modeling was used to derive trajectories of each exposure in each period. Logistic regression was used to examine associations with outcomes.

RESULTS: A total of 53 458 individuals (median [IQR] age at diagnosis in case patients, 23.2 [15.0-34.8] years; 30 746 [57.5%] female), including 26 729 case patients and 26 729 control participants, were studied. From birth to early adolescence, gradients were observed in exposure to deprivation and population density trajectories during upbringing and psychotic disorder, with those in the most vs least deprived (adjusted odds ratio [AOR], 1.17; 95% CI, 1.08-1.28) and most vs least densely populated (AOR, 1.49; 95% CI, 1.34-1.66) trajectories at greatest risk. A strong upward mobility trajectory to less deprived neighborhoods was associated with similar risk to living in the least deprived trajectory (AOR, 1.01; 95% CI, 0.91-1.12). Only 543 case patients (2.0%) drifted into more deprived areas after diagnosis; people with psychotic disorder were more likely to belong to this trajectory (AOR, 1.38; 95% CI, 1.16-1.65) or remain in the most deprived trajectory (AOR, 1.36; 95% CI, 1.24-1.48) relative to controls. Patterns were similar for nonpsychotic bipolar disorder and deprivation but weaker for population density.

CONCLUSIONS AND RELEVANCE: In this case-control study, greater exposure to deprivation during upbringing was associated with increased risk of serious mental illness, but upward mobility mitigated this association. People with serious mental illness disproportionately remained living in more deprived areas after diagnosis, highlighting issues of social immobility. Prevention and treatment should be proportionately located in deprived areas according to need.

PMID:37672257 | DOI:10.1001/jamapsychiatry.2023.3220

JAMA Dermatol. 2023 Sep 6. doi: 10.1001/jamadermatol.2023.3003. Online ahead of print.

ABSTRACT

IMPORTANCE: Growing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals with cancer who receive immune checkpoint inhibitor (ICI) treatment.

OBJECTIVE: To identify whether the presence of cirAEs and their subtypes subsequent to ICI administration is associated with enhanced cancer prognosis.

DATA SOURCES: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications examining the association between cirAE development during ICI treatment and subsequent cancer prognosis. The initial search was limited to English-language publications from database inception until December 31, 2022; a subsequent search was performed on May 21, 2023.

STUDY SELECTION: Two reviewers independently scrutinized the identical articles and included those that constituted original research evaluating the association between cirAE development and cancer prognosis.

DATA EXTRACTION AND SYNTHESIS: The search terms, study objectives, and methodological protocols were defined before study initiation. The aforementioned 2 reviewers performed data extraction independently and resolved discrepancies through agreement. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines. The protocol was prospectively registered with PROSPERO. Data analyses were conducted between May 21 and June 1, 2023.

MAIN OUTCOMES AND MEASURES: The major outcome end points were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were also conducted according to cirAE type, cancer type, geographic region, study design, and ICI type. Given the heterogeneity inherent in the included studies, a DerSimonian-Laird random-effects model was adopted.

RESULTS: This systematic review and meta-analysis included 23 studies with a total of 22 749 patients treated with ICIs. The occurrence of cirAEs was associated with improved OS (hazard ratio [HR], 0.61 [95% CI, 0.52-0.72]; P < .001) and PFS (HR, 0.52 [95% CI, 0.41-0.65]; P < .001). Consistent results were observed across all subgroups stratified by study design, geographic region, ICI type, and cancer type, aligning with the overall estimate of OS and PFS improvement. However, no statistically significant differences were identified in terms of PFS within studies conducted in the US.

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, the presence of cirAEs and their subtypes was associated with improved prognosis for individuals with cancer undergoing ICI treatment. These findings suggest that cirAEs may have useful prognostic value in ICI treatment.

PMID:37672255 | DOI:10.1001/jamadermatol.2023.3003

JAMA Psychiatry. 2023 Sep 6. doi: 10.1001/jamapsychiatry.2023.3145. Online ahead of print.

ABSTRACT

IMPORTANCE: Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence.

OBJECTIVE: To assess the purpose and associated risks of off-label gabapentin use in OUD treatment.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day.

EXPOSURES: Days covered by filled gabapentin prescriptions.

MAIN OUTCOMES AND MEASURES: Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.

RESULTS: A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage.

CONCLUSIONS AND RELEVANCE: Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.

PMID:37672238 | DOI:10.1001/jamapsychiatry.2023.3145

Minerva Pediatr (Torino). 2023 Sep 6. doi: 10.23736/S2724-5276.23.07360-3. Online ahead of print.

ABSTRACT

BACKGROUND: Despite recent improvements, premature infants remain at high risk for long-term morbidity and poorer neurodevelopment, particularly very preterm (VP) and very low birth weight (VLBW). The aim of this study was to describe neurodevelopmental outcomes at two years and identify potential predictors of worse performance.

METHODS: In a retrospective cohort, a two-years’ neurodevelopmental evaluation was analyzed. Multivariable regressions were used to study the association of perinatal history with neurodevelopmental outcomes. Subjects included VP and/or VLBW born at a Portuguese III-level perinatal center between 2011-2017. Milestones outcomes were assessed using the Griffiths’ Mental Development Scales.

RESULTS: One hundred seventy-seven infants were included. Two-years milestones were not achieved in 18.6% in language domain and 7.3% in motor function, 4.5% wore glasses and 1.1% auditory prosthesis/cochlear implant. Almost 30% needed intervention, 18.6% occupational therapy, 16.4% physiotherapy and 13.6% speech therapy. Griffiths’ Mental Development Scales was performed in 139, with a mean global quotient of 98.3 and hearing/speech as the least quoted scale. Global development delay (GDD) was present in 14.8% and cerebral palsy in 2.8%. Multivariate analysis by logistic regression adjusted to gestational age, birth weight and confounding variables, revealed a statistically significant association between GDD and hydrocephalus with shunt/reservoir (OR:19.01), retinopathy of prematurity stage ≥2 (OR:7.86) and neonatal sepsis (OR:3.34).

CONCLUSIONS: Consistent with recent studies, preterm are at increased risk of neurodevelopmental impairment, mainly due to GDD and language delay, rather than cerebral palsy. In this population, hydrocephalus, retinopathy of prematurity and neonatal sepsis were strongly associated with poorer outcomes. Insight into these factors is essential to refer patients for specific early intervention programs.

PMID:37672234 | DOI:10.23736/S2724-5276.23.07360-3

Hum Mol Genet. 2023 Sep 6:ddad142. doi: 10.1093/hmg/ddad142. Online ahead of print.

ABSTRACT

The myocyte enhancer factor 2 C (MEF2C) gene encodes a transcription factor important for neurogenesis and synapse development and contains common variants associated with intelligence (IQ) and educational attainment (EA). Here, we took gene expression data from the mouse cortex of a Mef2c mouse model with a heterozygous DNA binding-deficient mutation of Mef2c (Mef2c-het) and combined these data with MEF2C ChIP-seq data from cortical neurons and single-cell data from the mouse brain. This enabled us to create a set of genes that were differentially regulated in Mef2c-het mice, represented direct target genes of MEF2C and had elevated in expression in cortical neurons. We found this gene-set to be enriched for genes containing common genetic variation associated with IQ and EA. Genes within this gene-set that were down-regulated, i.e. have reduced expression in Mef2c-het mice versus controls, were specifically significantly enriched for both EA and IQ associated genes. These down-regulated genes were enriched for functionality in the adenylyl cyclase signalling system, which is known to positively regulate synaptic transmission and has been linked to learning and memory. Within the adenylyl cyclase signalling system, three genes regulated by MEF2C, CRHR1, RGS6, and GABRG3, are associated at genome-wide significant levels with IQ and/or EA. Our results indicate that genetic variation in MEF2C and its direct target genes within cortical neurons contribute to variance in cognition within the general population, and the molecular mechanisms involved include the adenylyl cyclase signalling system’s role in synaptic function.

PMID:37672226 | DOI:10.1093/hmg/ddad142

Clin Pharmacokinet. 2023 Sep 6. doi: 10.1007/s40262-023-01282-y. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and hospitalization due to heart failure. A dedicated QTc study in patients with chronic coronary syndromes demonstrated no clinically relevant QTc effect of vericiguat for exposures across the therapeutic dose range (2.5-10 mg). Interval prolongation concentration-QTc (C-QTc) modeling was performed to complement the statistical evaluations of QTc in the dedicated QTc study.

METHODS: Individual time-matched, baseline- and placebo-corrected Fridericia-corrected QT interval values (ΔΔQTcF) were derived. Two approaches for ΔΔQTcF calculation were investigated: (1) ΔΔQTcF correction with data from a single baseline (as in the primary statistical analysis); and (2) ΔΔQTcF correction with a modeled baseline (considering all available individual non-treatment baselines). The ΔΔQTcF values were related to observed vericiguat concentrations with linear mixed-effects modeling.

RESULTS: For both modeling approaches, a positive relationship was found between ΔΔQTcF and vericiguat concentration; however, the slope for the single-baseline approach was not statistically significant, whereas the slope from the modeled-baseline approach was statistically significant. The upper bound of the two-sided 90% confidence interval for model-derived QTc was < 10 ms at the highest observed exposure (745 μg/L; investigated dose range 2.5-10 mg).

CONCLUSION: By applying a single-baseline approach and a modeled-baseline approach that integrated all available QTc data across doses to characterize the QTc prolongation potential, this study showed that vericiguat 2.5-10 mg is not associated with clinically relevant QTc effects, in line with the conclusion from the primary statistical analysis.

CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov NCT03504982.

PMID:37672197 | DOI:10.1007/s40262-023-01282-y

J Racial Ethn Health Disparities. 2023 Sep 6. doi: 10.1007/s40615-023-01755-7. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantify racial disparities in mortality and post-hospitalization outcomes among incarcerated individuals that were hospitalized during their incarceration period.

METHODS: We designed a retrospective cohort study using administrative and hospital data collected from a preferred healthcare referral center for all Massachusetts jails and prisons between January 2011 and December 2018 with linkage to Massachusetts Vital Records and Statistics. We identified 4260 incarcerated individuals with complete data on race/ethnicity that were hospitalized during the study period. The primary study indicators were age, race, ethnicity, length of hospital stay, Elixhauser comorbidity score, incarceration facility type, and number of hospital admissions. The primary outcome was time to death.

RESULTS: Of the incarcerated individuals that were hospitalized, 2606 identified as White, 1214 identified as Black, and 411 people who identified as some other race. The hazard of death significantly increased by 3% (OR: 1.03; 95% CI: 1.02-1.03) for each additional yearly increase in age. After adjusting for the interaction between race and age, Black race was significantly associated with 3.01 increased hazard (95% CI: 1.75-5.19) of death for individuals hospitalized while incarcerated compared to White individuals hospitalized while incarcerated. Hispanic ethnicity and being incarcerated in a prison facility was not associated with time to mortality, while increased mean Elixhauser score (HR: 1.07; 95% CI: 1.06-1.08) and ≥ 3 hospital admissions (HR: 2.47; 95% CI: 2.07-2.95) increased the hazard of death.

CONCLUSIONS: Our findings suggest disparities exist in the mortality outcomes among Black and White individuals who are hospitalized during incarceration, with an increased rate of death among Black individuals. Despite hypothesized equal access to healthcare within correctional facilities, our findings suggest that incarcerated and hospitalized Black individuals may experience worse disparities than their White counterparts, which has not been previously explored or reported in the literature. In addition to decarceration, advocacy, and political efforts, increased efforts to support research access to datasets of healthcare outcomes, including hospitalization and death, for incarcerated people should be encouraged. Further research is needed to identify and address the implicit and explicit sources of these racial health disparities across the spectrum of healthcare provision.

PMID:37672188 | DOI:10.1007/s40615-023-01755-7

Qual Life Res. 2023 Sep 6. doi: 10.1007/s11136-023-03506-x. Online ahead of print.

ABSTRACT

PURPOSE: Tuberculosis (TB) has far-reaching effects on the social, mental, and emotional well-being of patients and consequently, their health-related quality of life (HRQOL). Few studies in Nigeria have examined changes in quality of life over the course of treatment. changes in (PTB) and factors associated with HRQOL.

METHODS: A prospective cohort study was conducted with patients recruited from health facilities in Lagos State. The World Health Organization Quality of Life Instrument, Short-Form (WHOQOL-BREF) was used to assess HRQOL. A semi-structured questionnaire was also administered to elicit information on socio-demographic characteristics and the medical and social history of the respondents. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 23. A repeated measures analysis of variance (ANOVA) test with polynomial contrasts was used to assess how domain scores varied over time. Multivariable analysis was conducted using generalized estimating equations (GEE) to assess change in HRQOL and its predictors.

RESULTS: Two hundred and ten patients, predominantly male [108 (63.3%)] were recruited. The mean age was 36.7 ± 12.3 years. The HRQOL was impaired in all four domains at baseline. However, HRQOL scores increased over the treatment period with the largest improvement being in the ‘environment’ domain, where mean scores increased from 45.27 ± 14.59 to 61.28 ± 15.86. The proportion of respondents that expressed satisfaction with their health increased from 13.5% at baseline to 55.7% at the end of treatment. Low socio-economic status, delay in presentation, and an HIV-positive status were found to be significantly associated with reduced HRQOL at baseline (p < 0.05). In the multivariable longitudinal analysis, patients who were employed had higher HRQOL scores while persistent symptoms and a delay in presentation (≥ 4 weeks) were negatively associated with change in HRQOL scores over the course of treatment.

CONCLUSION: The HRQOL of respondents progressively improved over the six-month treatment period. However, change in HRQOL was influenced by a delay in presentation and persistence of symptoms. The study also highlights the need for increased recognition of patient-reported outcomes as an adjunct outcome measure.

PMID:37672154 | DOI:10.1007/s11136-023-03506-x

Environ Monit Assess. 2023 Sep 6;195(10):1153. doi: 10.1007/s10661-023-11609-8.

ABSTRACT

Predicting crop yields, and especially anomalously low yields, is of special importance for food insecure countries. In this study, we investigate a flexible deep learning approach to forecast crop yield at the provincial administrative level based on deep 1D and 2D convolutional neural networks using limited data. This approach meets the operational requirements-public and global records of satellite data in an application ready format with near real time updates-and can be transferred to any country with reliable yield statistics. Three-dimensional histograms of normalized difference vegetation index (NDVI) and climate data are used as input to the 2D model, while simple administrative-level time series averages of NDVI and climate data to the 1D model. The best model architecture is automatically identified during efficient and extensive hyperparameter optimization. To demonstrate the relevance of this approach, we hindcast (2002-2018) the yields of Algeria’s three main crops (barley, durum and soft wheat) and contrast the model’s performance with machine learning algorithms and conventional benchmark models used in a previous study. Simple benchmarks such as peak NDVI remained challenging to outperform while machine learning models were superior to deep learning models for all forecasting months and all tested crops. We attribute the poor performance of deep learning to the small size of the dataset available.

PMID:37672152 | DOI:10.1007/s10661-023-11609-8

Eur J Orthop Surg Traumatol. 2023 Sep 6. doi: 10.1007/s00590-023-03712-w. Online ahead of print.

ABSTRACT

PURPOSE: This systematic review and meta-analysis aimed to investigate the correlation between anthropometric measurements and graft size in anterior cruciate ligament (ACL) reconstruction.

METHODS: A systematic search of Ovid MEDLINE, Embase, and Cochrane Library databases was conducted for observational studies published until March 2023 that reported the relationship between anthropometric data [height, weight, body mass index (BMI), age, gender, thigh length, and circumference] and ACL graft size. Correlation coefficients (COR) and their associated 95% confidence intervals were used as the primary effect size. This review was conducted in line with PRISMA guidelines.

RESULTS: A total of 42 observational studies involving 7110 patients were included, with a mean age of 29.8 years. Statistically significant, moderately positive correlations were found between graft size and height (COR: 0.49; 95% CI: 0.41-0.57; p-value: < 0.001), weight (COR: 0.38; 95% CI: 0.31-0.44; p-value: < 0.001), thigh circumference (COR: 0.40; 95% CI: 0.19-0.58; p-value: < 0.001), and thigh length (COR: 0.35; 95% CI: 0.18-0.50; p-value: < 0.001). However, age and gender were insignificantly correlated with graft size (p-value: NS). A subanalysis based on graft type showed a significant positive correlation between height and graft diameter, which was more significant in the peroneus tendon than in hamstring grafts (COR: 0.76 vs. 0.45; p-value: 0.020).

CONCLUSION: This study demonstrated a moderate positive correlation between anthropometric measurements (height, weight, thigh circumference, and length) and ACL graft size, along with a weak positive correlation with BMI. Age and gender showed no significant correlation. These findings support the predictability and selection of ACL graft size based on pre-operative patient anthropometric data.

LEVEL OF EVIDENCE: Level of Evidence: IV. PROSPERO registration number: CRD42023416044.

PMID:37672150 | DOI:10.1007/s00590-023-03712-w