Category: Nevin Manimala

Clin Orthop Relat Res. 2023 Jan 25. doi: 10.1097/CORR.0000000000002555. Online ahead of print.

ABSTRACT

BACKGROUND: The 2019 novel coronavirus (COVID-19) pandemic has been associated with poor mental health outcomes and widened health disparities in the United States. Given the inter-relationship between psychosocial factors and functional outcomes in orthopaedic surgery, it is important that we understand whether patients presenting for musculoskeletal care during the pandemic were associated with worse physical and mental health than before the pandemic’s onset.

QUESTIONS/PURPOSES: (1) Did patients seen for an initial visit by an orthopaedic provider during the COVID-19 pandemic demonstrate worse physical function, pain interference, depression, and/or anxiety than patients seen before the pandemic, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) instrument? (2) During the COVID-19 pandemic, did patients living in areas with high levels of social deprivation demonstrate worse patterns of physical function, pain interference, depression, or anxiety on initial presentation to an orthopaedic provider than patients living in areas with low levels of social deprivation, compared with prepandemic PROMIS scores?

METHODS: This was a retrospective, comparative study of new patient evaluations that occurred in the orthopaedic department at a large, urban tertiary care academic medical center. During the study period, PROMIS computer adaptive tests were routinely administered to patients at clinical visits. Between January 1, 2019, and December 31, 2019, we identified 26,989 new patients; we excluded 4% (1038 of 26,989) for being duplicates, 4% (1034 of 26,989) for having incomplete demographic data, 44% (11,925 of 26,989) for not having a nine-digit home ZIP Code recorded, and 5% (1332 of 26,989) for not completing all four PROMIS computer adaptive tests of interest. This left us with 11,660 patients in the “before COVID-19” cohort. Between January 1, 2021 and December 31, 2021, we identified 30,414 new patients; we excluded 5% (1554 of 30,414) for being duplicates, 4% (1142 of 30,414) for having incomplete demographic data, 41% (12,347 of 30,414) for not having a nine-digit home ZIP Code recorded, and 7% (2219 of 30,414) for not completing all four PROMIS computer adaptive tests of interest. This left us with 13,152 patients in the “during COVID-19” cohort. Nine-digit home ZIP Codes were used to determine patients’ Area Deprivation Indexes, a neighborhood-level composite measure of social deprivation. To ensure that patients included in the study represented our overall patient population, we performed univariate analyses on available demographic and PROMIS data between patients included in the study and those excluded from the study, which revealed no differences (results not shown). In the before COVID-19 cohort, the mean age was 57 ± 16 years, 60% (7046 of 11,660) were women, 86% (10,079 of 11,660) were White non-Hispanic, and the mean national Area Deprivation Index percentile was 47 ± 25. In the during COVID-19 cohort, the mean age was 57 ± 16 years, 61% (8051 of 13,152) were women, 86% (11,333 of 13,152) were White non-Hispanic, and the mean national Area Deprivation Index percentile was 46 ± 25. The main outcome measures in this study were the PROMIS Physical Function ([PF], version 2.0), Pain Interference ([PI], version 1.1), Depression (version 1.0), and Anxiety (version 1.0). PROMIS scores follow a normal distribution with a mean t-score of 50 and a standard deviation of 10. Higher PROMIS PF scores indicate better self-reported physical capability, whereas higher PROMIS PI, Depression, and Anxiety scores indicate more difficulty managing pain, depression, and anxiety symptoms, respectively. Clinically meaningful differences in PROMIS scores between the cohorts were based on a minimum clinically important difference (MCID) threshold of 4 points. Multivariable linear regression models were created to determine whether presentation to an orthopaedic provider during the pandemic was associated with worse PROMIS scores than for patients who presented before the pandemic. Regression coefficients (ß) represent the estimated difference in PROMIS scores that would be expected for patients who presented during the pandemic compared with patients who presented before the pandemic, after adjusting for confounding variables. Regression coefficients were evaluated in the context of clinical importance and statistical significance. Regression coefficients equal to or greater than the MCID of 4 points were considered clinically important, whereas p values < 0.05 were considered statistically significant.

RESULTS: We found no clinically important differences in baseline physical and mental health PROMIS scores between new patients who presented to an orthopaedic provider before the COVID-19 pandemic and those who presented during the COVID-19 pandemic (PROMIS PF: ß -0.2 [95% confidence interval -0.43 to 0.03]; p = 0.09; PROMIS PI: ß 0.06 [95% CI -0.13 to 0.25]; p = 0.57; PROMIS Depression: ß 0.09 [95% CI -0.14 to 0.33]; p = 0.44; PROMIS Anxiety: ß 0.58 [95% CI 0.33 to 0.84]; p < 0.001). Although patients from areas with high levels of social deprivation had worse PROMIS scores than patients from areas with low levels of social deprivation, patients from areas with high levels of social deprivation demonstrated no clinically important differences in PROMIS scores when groups before and during the pandemic were compared (PROMIS PF: ß -0.23 [95% CI -0.80 to 0.33]; p = 0.42; PROMIS PI: ß 0.18 [95% CI -0.31 to 0.67]; p = 0.47; PROMIS Depression: ß 0.42 [95% CI -0.26 to 1.09]; p = 0.23; PROMIS Anxiety: ß 0.84 [95% CI 0.16 to 1.52]; p = 0.02).

CONCLUSION: Contrary to studies describing worse physical and mental health since the onset of the COVID-19 pandemic, we found no changes in the health status of orthopaedic patients on initial presentation to their provider. Although large-scale action to mitigate the effects of worsening physical or mental health of orthopaedic patients may not be needed at this time, orthopaedic providers should remain aware of the psychosocial needs of their patients and advocate on behalf of those who may benefit from intervention. Our study is limited in part to patients who had the self-agency to access specialty orthopaedic care, and therefore may underestimate the true changes in the physical or mental health status of all patients with musculoskeletal conditions. Future longitudinal studies evaluating the impact of specific COVID-19-related factors (for example, delays in medical care, social isolation, or financial loss) on orthopaedic outcomes may be helpful to prepare for future pandemics or natural disasters.

LEVEL OF EVIDENCE: Level II, prognostic study.

PMID:36696142 | DOI:10.1097/CORR.0000000000002555

JAMA Dermatol. 2023 Jan 25. doi: 10.1001/jamadermatol.2022.6051. Online ahead of print.

ABSTRACT

IMPORTANCE: Lipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid-lowering drugs, such as statins, are hypothesized to have disease-modifying properties. However, large population-level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding.

OBJECTIVE: To investigate the causal association between genetically proxied lipid-lowering drugs and psoriasis risk.

DESIGN, SETTING, AND PARTICIPANTS: This 2-sample mendelian randomization study was performed from August to October 2022 and included population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies and low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium. The inverse variance-weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses.

EXPOSURES: Genetically proxied inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, eg, alirocumab), using LDL as the biomarker.

MAIN OUTCOMES AND MEASURES: Risk of psoriasis.

RESULTS: Data from 12 116 patients with psoriasis and approximately 1.3 million individuals with LDL measurement were analyzed. Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition.

CONCLUSIONS AND RELEVANCE: This mendelian randomization study suggests that PCSK9 is implicated in psoriasis pathogenesis, and its inhibition is associated with reduced psoriasis risk. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of psoriasis.

PMID:36696131 | DOI:10.1001/jamadermatol.2022.6051

JAMA Surg. 2023 Jan 25. doi: 10.1001/jamasurg.2022.7063. Online ahead of print.

ABSTRACT

IMPORTANCE: The stereotype that men perform surgery better than women is ancient. Surgeons have long been mainly men, but in recent decades an inversion has begun; the number of women surgeons is increasing, especially in obstetrics and gynecology. Studies outside obstetrics suggest that postoperative morbidity and mortality may be lower after surgery by women.

OBJECTIVE: To evaluate the association between surgeons’ gender and the risks of maternal morbidity and postpartum hemorrhage (PPH) after cesarean deliveries.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was based on data from the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, a multicenter, randomized, placebo-controlled trial that took place from March 2018 through January 2020 (23 months). It aimed to investigate whether the administration of tranexamic acid plus a prophylactic uterotonic agent decreased PPH incidence after cesarean delivery compared with a uterotonic agent alone. Women having a cesarean delivery before or during labor at or after 34 weeks’ gestation were recruited from 27 French maternity hospitals.

EXPOSURES: Self-reported gender (man or woman), assessed by a questionnaire immediately after delivery.

MAIN OUTCOMES AND MEASURES: The primary end point was the incidence of a composite maternal morbidity variable, and the secondary end point was the incidence of PPH (the primary outcome of the TRAAP2 trial), defined by a calculated estimated blood loss exceeding 1000 mL or transfusion by day 2.

RESULTS: Among 4244 women included, men surgeons performed 943 cesarean deliveries (22.2%) and women surgeons performed 3301 (77.8%). The rate of attending obstetricians was higher among men (441 of 929 [47.5%]) than women (687 of 3239 [21.2%]). The risk of maternal morbidity did not differ for men and women surgeons: 119 of 837 (14.2%) vs 476 of 2928 (16.3%) (adjusted risk ratio, 0.92 [95% CI, 0.77-1.13]). Interaction between surgeon gender and level of experience on the risk of maternal morbidity was not statistically significant. Similarly, the groups did not differ for PPH risk (adjusted risk ratio, 0.98 [95% CI, 0.85-1.13]).

CONCLUSIONS AND RELEVANCE: Risks of postoperative maternal morbidity and of PPH exceeding 1000 mL or requiring transfusion by day 2 did not differ by the surgeon’s gender.

PMID:36696127 | DOI:10.1001/jamasurg.2022.7063

JAMA Dermatol. 2023 Jan 25. doi: 10.1001/jamadermatol.2022.6085. Online ahead of print.

ABSTRACT

IMPORTANCE: Two recent meta-analyses reported a high prevalence of both anxiety and depression in patients with alopecia areata (AA), as well as a positive association of AA with anxiety and depression, without distinguishing between disorders and symptoms. Yet, depression and anxiety can manifest either as symptoms identified in questionnaires or as specific diagnoses defined by Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision criteria.

OBJECTIVE: To perform a large meta-analysis separating the prevalence of depressive and anxiety disorders from that of depressive and anxiety symptoms in patients with AA.

DATA SOURCES: PubMed, ScienceDirect, the Cochrane Library, Embase, and PsycINFO databases were searched from inception through August 1, 2020.

STUDY SELECTION: Studies that contained data on the prevalence of depressive or anxiety disorders or symptoms were included.

DATA EXTRACTION AND SYNTHESIS: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines were used. Pooled prevalence was calculated with a random effects model meta-analysis that took into account between- and within-study variability. Meta-regressions were used to study the association between variations in prevalence and study characteristics.

MAIN OUTCOMES AND MEASURES: The prevalence of depressive and anxiety disorders and symptoms in patients with AA.

RESULTS: Thirty-seven articles (29 on depression and 26 on anxiety) that met the inclusion criteria were identified. By distinguishing between disorders and symptoms, the prevalence of both depressive disorders (9%) and unspecified anxiety disorders (13%) in patients with AA was shown to be greater than that in the general population. The prevalence and odds ratio (OR) of depressive disorders (prevalence, 9%; OR, 1.38) and anxiety disorders of which each category had been specifically studied (prevalence, 7%-17%; OR, 1.51-1.69) were markedly lower than that of depressive symptoms (prevalence, 37%; OR, 2.70) and anxiety symptoms (prevalence, 34%; OR, 3.07). Meta-regressions showed that variations in prevalence were mainly associated with methodological differences between studies.

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, the separate analyses showed that 7% to 17% of patients with AA had depressive or anxiety disorders that require psychiatric care, including specific medication. Additionally, more than one-third of patients had symptoms that are warning signs and that need monitoring because they can develop into disorders.

PMID:36696123 | DOI:10.1001/jamadermatol.2022.6085

JAMA Netw Open. 2023 Jan 3;6(1):e2252689. doi: 10.1001/jamanetworkopen.2022.52689.

ABSTRACT

IMPORTANCE: Psychosis is a hypothesized consequence of cannabis use. Legalization of cannabis could therefore be associated with an increase in rates of health care utilization for psychosis.

OBJECTIVE: To evaluate the association of state medical and recreational cannabis laws and commercialization with rates of psychosis-related health care utilization.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort design using state-level panel fixed effects to model within-state changes in monthly rates of psychosis-related health care claims as a function of state cannabis policy level, adjusting for time-varying state-level characteristics and state, year, and month fixed effects. Commercial and Medicare Advantage claims data for beneficiaries aged 16 years and older in all 50 US states and the District of Columbia, 2003 to 2017 were used. Data were analyzed from April 2021 to October 2022.

EXPOSURE: State cannabis legalization policies were measured for each state and month based on law type (medical or recreational) and degree of commercialization (presence or absence of retail outlets).

MAIN OUTCOMES AND MEASURES: Outcomes were rates of psychosis-related diagnoses and prescribed antipsychotics.

RESULTS: This study included 63 680 589 beneficiaries followed for 2 015 189 706 person-months. Women accounted for 51.8% of follow-up time with the majority of person-months recorded for those aged 65 years and older (77.3%) and among White beneficiaries (64.6%). Results from fully-adjusted models showed that, compared with no legalization policy, states with legalization policies experienced no statistically significant increase in rates of psychosis-related diagnoses (medical, no retail outlets: rate ratio [RR], 1.13; 95% CI, 0.97-1.36; medical, retail outlets: RR, 1.24; 95% CI, 0.96-1.61; recreational, no retail outlets: RR, 1.38; 95% CI, 0.93-2.04; recreational, retail outlets: RR, 1.39; 95% CI, 0.98-1.97) or prescribed antipsychotics (medical, no retail outlets RR, 1.00; 95% CI, 0.88-1.13; medical, retail outlets: RR, 1.01; 95% CI, 0.87-1.19; recreational, no retail outlets: RR, 1.13; 95% CI, 0.84-1.51; recreational, retail outlets: RR, 1.14; 95% CI, 0.89-1.45). In exploratory secondary analyses, rates of psychosis-related diagnoses increased significantly among men, people aged 55 to 64 years, and Asian beneficiaries in states with recreational policies compared with no policy.

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of commercial and Medicare Advantage claims data, state medical and recreational cannabis policies were not associated with a statistically significant increase in rates of psychosis-related health outcomes. As states continue to introduce new cannabis policies, continued evaluation of psychosis as a potential consequence of state cannabis legalization may be informative.

PMID:36696111 | DOI:10.1001/jamanetworkopen.2022.52689

JAMA Psychiatry. 2023 Jan 25. doi: 10.1001/jamapsychiatry.2022.4350. Online ahead of print.

ABSTRACT

IMPORTANCE: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers.

OBJECTIVE: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health-related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020.

MAIN OUTCOMES AND MEASURES: Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry.

RESULTS: Blood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P < 10-38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P < 10-79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids.

CONCLUSIONS AND RELEVANCE: In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.

PMID:36696101 | DOI:10.1001/jamapsychiatry.2022.4350

Probiotics Antimicrob Proteins. 2023 Jan 25. doi: 10.1007/s12602-023-10043-z. Online ahead of print.

ABSTRACT

Probiotics are beneficial bacteria that may modulate the immune response by altering the maturation and function of antigen-presenting cells, such as dendritic cells. This study aimed to evaluate the antibacterial gene expression of dendritic cells challenged with LPS and probiotics. Immature dendritic cells were obtained from human CD14⁺ monocytes and challenged with E. coli LPS and probiotics Lacticaseibacillus rhamnosus (LR-32) and Lactobacillus acidophilus (LA-5) at a ratio DC:bacteria of 1:10. The analysis of gene expression was performed by RT-qPCR using the Kit RT2 human antibacterial response. In the supernatant, the cytokines secretion was determined by ELISA. Tukey post-ANOVA with p at 5% was used for statistical analysis. LPS showed the higher upregulation of 29 genes compared with the groups where probiotics were added to LPS, including genes related to an inflammatory response like BIRC3, CASP1, CCL5, CXCL1, IL12B, IL18, MYD88, NLRP3, RIPK1, and TIRAP. Similarly, LPS increased the transcription of genes enrolled with apoptosis such as CARD6, CASP1, IRF5, MAP2K1, MAP2K4, MAPK1, MYD88, NLRP3, RIPK2, TNF, TNFRSF1A, and XIAP when compared to probiotics groups (p < 0.05). Although probiotics decrease several genes upregulated by LPS, the transcription of encoded cytokines IL12A, IL12B, IL1B, IL6, CXCL8, and TNF genes was maintained upregulated by probiotics, except for IL18, which was downregulated by LA-5. LA-5 led to a higher transcription of IL1B, IL6, and CXCL-8 which was followed by the secretion of these proteins by ELISA. The results suggest that probiotics attenuate the transcription of inflammatory and immune response genes caused by LPS.

PMID:36696085 | DOI:10.1007/s12602-023-10043-z

Environ Sci Pollut Res Int. 2023 Jan 25. doi: 10.1007/s11356-023-25415-9. Online ahead of print.

ABSTRACT

In the current era of business, environmental sustainability has emerged as an issue of critical relevance. The main purpose of this study is to examine the relationship between environmental leadership and environmental learning and its impact on the organization’s performance. This research contributes to the existing body of knowledge by identifying the primary characteristics that help companies enhance their performance. Using a convenience sample approach, data was obtained from 417 respondents working in the construction industry. For direct and indirect hypothesis testing, we used the Statistical Package for the Social Sciences (SPSS) and structural equation modelling (SEM). According to the study’s findings, environmental leadership (EL) and environmental knowledge learning (EKL) significantly influence environmental passion (EP), green corporate social responsibility (CSR), and company performance. The link between EL, EKL, and firm performance (FP) is mediated by EP. The study’s results indicate that green CSR significantly moderates the relationship between EP and firm performance. The study findings benefit business managers, policymakers, and government institutions.

PMID:36696059 | DOI:10.1007/s11356-023-25415-9

Genes Genomics. 2023 Jan 25. doi: 10.1007/s13258-022-01361-7. Online ahead of print.

ABSTRACT

BACKGROUND: Microsoft Excel has substantial functionalities for data management and analyses, and has been the most popular software in this field. However, in spite of Excel’s user-friendly interface and functionality for data management, it provides very few functions for in-depth statistical analyses, which has limited its wider application for this purpose.

OBJECTIVE: Here, we introduce Rex, an Excel add-in software implementing the powerful analytical and graphical functions of R within Excel.

METHODS: Rex was implemented using three types of programming software: R, JavaScript, and Microsoft VB.Net.

RESULTS: Rex provides a graphical user interface (GUI) through Excel, and statistical analysis can be conducted by pointing and clicking the menu without programming R. Rex covers a wide range of analyses from basic statistics to advanced analysis, including structural equation modeling, complex sampling design, and machine learning models, making it possible for researchers not skilled in using a command-line interface to conduct in-depth statistical analyses. Most Rex modules are available in a free version for non-commercial use, and it can be used for educational and public purposes.

CONCLUSION: In this article, we introduce the framework and features of Rex with illustrative examples of its implementation.

PMID:36696053 | DOI:10.1007/s13258-022-01361-7

Ann Surg Oncol. 2023 Jan 25. doi: 10.1245/s10434-023-13099-x. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple composite indices of small-area socioeconomic characteristics have been used to examine how neighborhood characteristics influence cancer care, but there is little consensus regarding how to use them. This scoping review aimed to summarize the use of these indices in cancer literature and their association with outcomes.

METHODS: A search was conducted to identify studies from 2015 to 2021 that investigated cancer incidence, disease stage at diagnosis, and mortality using area-based indices of deprivation as an independent variable. Studies were screened and assessed for eligibility. Data were extracted regarding the geospatial and statistical use of these indices.

RESULTS: All the inclusion criteria were met by 45 studies. The area level of analysis was at the census tract level in 19 studies (42.3%), the county level in 15 studies (33.3%), the block group level in 6 studies (13.3%), and the ZIP code level in 5 studies (11.1%). Altogether, 18 unique indices were used, with 4 indices used most frequently. Of the studies that used their indices ordinally, 3 defined high and low deprivation dichotomously, 10 used tertiles, 13 used quartiles, and 15 used quintiles. Of the 45 studies, 34 (76%) showed a significant association between area deprivation and cancer-related outcomes.

CONCLUSIONS: Neighborhood deprivation indices are most commonly used at the census tract level and ordinally as quintiles. Despite variance in methods, there is a strong indication that deprived areas are at adverse odds with cancer-related outcomes. Further study investigating deprivation in the context of cancer can inform drivers of inequity and identify potential targets for care delivery and policy interventions.

PMID:36695989 | DOI:10.1245/s10434-023-13099-x