Category: Nevin Manimala

Lancet Glob Health. 2023 Mar;11 Suppl 1:S1. doi: 10.1016/S2214-109X(23)00086-4.

ABSTRACT

BACKGROUND: Five novel subtypes of adult-onset diabetes were identified in 2018. We aimed to investigate whether childhood adiposity increases the risks of these subtypes using a Mendelian randomisation design, and to explore genetic overlaps between body size (self-reported perceived body size [ie, thinner, about average, or plumper] in childhood, and BMI measured in adulthood) and these subtypes.

METHODS: The Mendelian randomisation and genetic correlation analyses were based on summary statistics from European genome-wide association studies of childhood body size (n=453 169), adult BMI (n=359 983), latent autoimmune diabetes in adults (n=8581), severe insulin-deficient diabetes (n=3937), severe insulin-resistant diabetes (n=3874), mild obesity-related diabetes (n=4118), and mild age-related diabetes (n=5605). We identified 267 independent genetic variants as instrumental variables for childhood body size in the Mendelian randomisation analysis of latent autoimmune diabetes in adults and 258 independent genetic variants as instrumental variables for other diabetes subtypes. The inverse variance-weighted method was used as the primary estimator in the Mendelian randomisation analysis, supplemented by other Mendelian randomisation estimators. We calculated overall genetic correlations (rg) between childhood or adult adiposity and different subtypes using linkage disequilibrium score regression.

FINDINGS: A large childhood body size was associated with increased risk of latent autoimmune diabetes in adults (odds ratio [OR] 1·62, 95% CI 1·95-2·52), severe insulin-deficient diabetes (OR 2·45, 1·35-4·46), severe insulin-resistant diabetes (OR 3·08, 1·73-5·50), and mild obesity-related diabetes (OR 7·70, 4·32-13·7), but not mild age-related diabetes in the main Mendelian randomisation analysis. Other Mendelian randomisation estimators gave similar results and did not support the existence of horizontal pleiotropy. There was genetic overlap between childhood body size and mild obesity-related diabetes (rg 0·282; p=0·0003), and between adult BMI and all diabetes subtypes.

INTERPRETATION: This study provides genetic evidence that higher childhood adiposity is a risk factor for all subtypes of adult-onset diabetes, except mild age-related diabetes. It is therefore important to prevent and intervene in childhood overweight or obesity. There is shared genetic contribution to childhood obesity and mild obesity-related diabetes.

FUNDING: The study was supported by the China Scholarship Council, the Swedish Research Council (grant number 2018-03035), Research Council for Health, Working Life and Welfare (grant number 2018-00337), and Novo Nordisk Foundation (grant number NNF19OC0057274).

PMID:36866468 | DOI:10.1016/S2214-109X(23)00086-4

Oncologist. 2023 Mar 2:oyad025. doi: 10.1093/oncolo/oyad025. Online ahead of print.

ABSTRACT

BACKGROUND: In 2020, pembrolizumab was approved as a therapy for triple-negative breast cancer (TNBC) with the companion diagnostic DAKO 22C3 programmed death ligand-1 (PD-L1) immunohistochemistry assay. The study aimed to determine the landscape of PD-L1 expression as detected by the DAKO 22C3 PD-L1 assay in breast cancer subtypes and compare the clinicopathologic and genomic characteristics of PD-L1 positive and negative TNBC.

METHODS: PD-L1 expression using the DAKO 22C3 antibody was scored using a combined positive score (CPS) and positive status was defined as CPS ≥10. Comprehensive genomic profiling was performed using the FoundationOne CDx assay.

RESULTS: Of the 396 BC patients stained with DAKO 22C3, the majority were HR+/HER2- and TNBC (42% and 36%, respectively). Median PD-L1 expression and frequency of CPS ≥10 was highest in TNBC cases (median: 7.5, 50% CPS ≥10) and lowest in the HR+/HER2- group (median: 1.0, 15.5% CPS ≥10) (P < .0001). A comparison of PD-L1 positive and PD-L1 negative TNBC demonstrated no significant differences in clinicopathologic or genomic characteristics. TNBC tissue samples from the breast did have an observed enrichment for PD-L1 positivity compared to TNBC tissue samples from a metastatic site (57% vs. 44%), but this was not statistically significant (P = .1766). In the HR+/HER2- group, genomic alterations in TP53, CREBBP, and CCNE1 were more prevalent and genomic loss of heterozygosity was higher in the PD-L1(+) group compared to the PD-L1(-) group.

CONCLUSIONS: The subtypes of breast cancer have distinct patterns of PD-L1 expression, supporting that further research of immunotherapies may include specific evaluation of optimum cutoffs for non-TNBC patients. In TNBC, PD-L1 positivity is not associated with other clinicopathologic or genomic features and should be integrated into future studies of immunotherapy efficacy.

PMID:36866462 | DOI:10.1093/oncolo/oyad025

Perm J. 2023 Mar 3:1-9. doi: 10.7812/TPP/22.145. Online ahead of print.

ABSTRACT

Introduction Alcohol screening and brief intervention has been shown to reduce unhealthy alcohol use, although widespread adoption into primary care practice has been slow. Patients undergoing bariatric surgery are at an increased risk of unhealthy alcohol use. The authors compared a novel, web-based screening tool called ATTAIN to usual care for real-world effectiveness and accuracy among bariatric surgery registry patients. Methods The authors analyzed the results of a quality improvement project that tested ATTAIN among bariatric surgery registry patients. Participants were stratified into 3 groups by surgery status (preoperative vs postoperative) and prior screening for unhealthy alcohol use (screened vs not screened in the past year). Participants in these 3 groups were divided into intervention plus usual care (n = 2249) and control (n = 2130) groups, with intervention being an email to complete ATTAIN, and control being usual care (eg, office-based screening). Primary outcomes included screening and positivity rates for unhealthy drinking behavior between groups. Secondary outcomes included positivity rates via ATTAIN vs usual care for individuals who were screened by both modalities. Chi-square test was used for statistical analysis. Results The overall screening rates were 67.4% (intervention arm) and 38.6% (control). The ATTAIN response rate was 47% of those invited. The overall positive screen rate was 7.7% (intervention) and 2.6% (control); p < .001 for both. For dual screened intervention participants, the positive screen rate was 10% (ATTAIN) vs 2% (usual care) with p < .001. Conclusion ATTAIN is a promising method of increasing screening and detection rates for unhealthy drinking behavior.

PMID:36866440 | DOI:10.7812/TPP/22.145

HERD. 2023 Mar 2:19375867231159130. doi: 10.1177/19375867231159130. Online ahead of print.

ABSTRACT

AIM: To examine how the spatial topology of the operating room (OR) within the medical center impacts surgical team communication.

BACKGROUND: Understanding the complex association between surgical team communication and the OR’s spatial network location is critical to patient safety. Effective surgical communication is associated with fewer adverse events and medical errors.

METHODS: We employed a cross-sectional, quantitative, case study, and network-centric study design. We studied the population of 204 clinicians in a large military medical center (36 perioperative nurses, 34 surgical technicians, 62 anesthesia providers, and 72 surgeons), focusing on surgical teams with cases completed within duty hours. Data were collected from December 2020 to June 2021 using an electronic survey. Spatial network analysis was done using electronic floor plans. Statistical analysis was done with descriptive statistics and linear regressions. The outcomes were general and task-specific communication, and team-level variables were aggregated from scores for all team members. Spatial effects were assessed with network centrality (degree, Laplacian, and betweenness).

RESULTS: The individual-level survey response rate was 77% (157 of 204). Data were collected on 137 surgical teams. On a 5-point scale, general and task-specific communication ranged from 3.4 to 5.0 and 3.5 to 5.0, respectively (for both, median = 4.7). Team size ranged from 4 to 6 individuals (median = 4). Surgical suites with higher network centralities were associated with significantly lower communication scores.

CONCLUSIONS: The OR’s spatial network location has important impacts on surgical team communication. Our findings have design and workflow implications for ORs and even surgical care in combat zones.

PMID:36866407 | DOI:10.1177/19375867231159130

J Public Health (Oxf). 2023 Feb 23:fdac169. doi: 10.1093/pubmed/fdac169. Online ahead of print.

ABSTRACT

AIM: The present study investigated regional differences in response behaviour for the Patient Health Quetionnaire-9. We tested for measurement invariance and differential item and test functioning between formerly divided East- and West-Germany: the former German Democratic Republic and Federal Republic of Germany. Diverging socialization experiences in socialist versus capitalist and collectivist versus individualist systems may affect culturally sensitive assessments of mental health.

SUBJECT AND METHODS: To test this empirically, we used factor analytic and item-response-theoretic frameworks, differentiating between East- and West-Germans by birthplace and current residence based on several representative samples of the German general population (n = 3 802).

RESULTS: Across all survey, we discovered slightly higher depression sum scores for East- versus West-Germans. The majority of items did not display differential item functioning-with a crucial exception in the assessment of self-harm tendencies. The scale scores were largely invariant exhibiting only small amounts of differential test functioning. Nonetheless, they made up on average about a quarter of the observed group differences in terms of effect magnitude.

CONCLUSION: We explore possible causes and discuss explanations for the item-level differences. Overall, analyses of East- and West-German depressive symptom developments in the wake of reunification are feasible and statistically grounded.

PMID:36866396 | DOI:10.1093/pubmed/fdac169

J Clin Hypertens (Greenwich). 2023 Mar 2. doi: 10.1111/jch.14646. Online ahead of print.

ABSTRACT

Although the effect of intensive systolic blood pressure lowering is widely recognized, treatment-related low diastolic blood pressure still worrisome. This was a prospective cohort study based on the National Health and Nutrition Examination Survey. Adults (≥20 years old) with guideline-recommended blood pressure were included and pregnant women were excluded. Survey-weighted logistic regression and cox models were used for analysis. A total of 25 858 participants were included in this study. After weighted, the overall mean age of the participants was 43.17 (16.03) years, including 53.7% women and 68.1% non-Hispanic white. Numerous factors were associated with low DBP (<60 mmHg), including advanced age, heart failure, myocardial infarction, and diabetes. The use of antihypertensive drugs was also associated with lower DBP (OR, 1.52; 95% CI, 1.26-1.83). DBP of less than 60 mmHg were associated with a higher risk of all-cause death (HR, 1.30; 95% CI, 1.12-1.51) and cardiovascular death (HR, 1.34; 95% CI, 1.00-1.79) compared to those with DBP between 70 and 80 mmHg. After regrouping, DBP <60 mmHg (no antihypertensive drugs) was associated with a higher risk of all-cause death (HR, 1.46; 95% CI, 1.21-1.75). DBP <60 mmHg after taking antihypertensive drugs was not associated with a higher risk of all-cause death (HR, 0.99; 95% CI, 0.73-1.36). Antihypertensive drug is an important factor contributing to DBP below 60 mmHg. But the pre-existing risk does not increase further with an additional reduction of DBP after antihypertensive drugs treatment.

PMID:36866395 | DOI:10.1111/jch.14646

Int J Ment Health Nurs. 2023 Mar 2. doi: 10.1111/inm.13131. Online ahead of print.

ABSTRACT

Globally, around half (55%) of the population live in fast-paced urban settings where many people find it challenging to manage their stress and respond to crises with a positive mindset. This resulted in prolonged distress where anxiety and fatigue caused physical and mental health concerns. Nature walks involving immersive exposure in the forest, and green spaces have been posited to offer physiological and psychological benefits. Therefore, in this systematic review, we evaluated the effects of forest bathing on psychological and physiological outcomes. We searched four English and five non-English databases (Chinese and Korean) for peer-reviewed studies published between January 2000 and March 2021. This review adhered to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analysis Statement 2020. The primary outcomes explored in this review were mainly psychological, including anxiety, depression, mood and quality of life. The secondary outcomes were physiological outcomes such as blood pressure and heart rate. We conducted a meta-analysis on each outcome using the random-effects model. Heterogeneity was assessed by the I² statistic. Thirty-six articles (21 in English, 3 in Chinese and 12 in Korean) with 3554 participants were included in this review. Our meta-analysis suggested that forest bathing can significantly reduce symptoms of depression and anxiety. However, we did not observe as many benefits in physiological outcomes. Against the background of the negative effects of urbanization on mental well-being, this review highlighted the potential therapeutic role of forests in the contemporary world, lending further evidence-based support for forest conservation.

PMID:36864583 | DOI:10.1111/inm.13131

Magn Reson Med. 2023 Mar 2. doi: 10.1002/mrm.29620. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the feasibility of combining simultaneous multislice (SMS) and region-optimized virtual coils (ROVir) for single breath-hold CINE imaging.

METHOD: ROVir is a recent virtual coil approach that allows reduced-field of view (FOV) imaging by localizing the signal from a region-of-interest (ROI) and/or suppressing the signal from unwanted spatial regions. In this work, ROVir is used for reduced-FOV SMS bSSFP CINE imaging, which enables whole heart CINE with a single breath-hold acquisition.

RESULTS: Reduced-FOV CINE with either SMS-only or ROVir-only resulted in significant aliasing, with severely reduced image quality when compared to the full FOV reference CINE, while the visual appearance of aliasing was substantially reduced with the proposed SMS+ROVir. The end diastolic volume, end systolic volume, and ejection fraction obtained using the proposed approach were similar to the clinical reference (correlations of 0.92, 0.94, and 0.88, respectively with in each case, and biases of 0.1, 1.6 mL, and $–0.6\%$ , respectively). No statistically significant differences for these parameters were found with a Wilcoxon rank test (p = 0.96, 0.20, and 0.40, respectively).

CONCLUSION: We demonstrated that reduced-FOV CINE imaging with SMS+ROVir enables single breath-hold whole-heart imaging without compromising visual image quality or quantitative cardiac function parameters.

PMID:36864561 | DOI:10.1002/mrm.29620

Orthop Surg. 2023 Mar 2. doi: 10.1111/os.13693. Online ahead of print.

ABSTRACT

OBJECTIVE: The optimal repair method for bursal-side partial-thickness rotator cuff tears (PTRCTs) involving >50% of the thickness remains a controversial topic. The study was aimed to compare the functional and magnetic resonance imaging (MRI) outcomes after in situ repair or tear completion before repair of bursal-side PTRCTs.

METHODS: A retrospective clinical study was conducted involving 58 patients who underwent in situ repair or tear completion before repair of bursal-side PTRCTs between January 2019 and December 2020. These patients were divided into two groups: the in situ repair group and the tear completion before repair group. Functional assessment consisted of active range of motion (ROM), visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, and Constant-Murley score. The percentages of patients in each group achieving the minimal clinical important difference (MCID) of the functional scores were determined. The healing status of the rotator cuff was assessed by postoperative MRI.

RESULTS: There were no statistically significant differences between the two groups in terms of demographic data. The mean follow-up period was 14.53 ± 2.64 months in the in situ repair group and 15.40 ± 2.66 months in the tear completion before repair group. At the final follow-up, the forward elevation, external rotation, and internal rotation improved significantly in both groups. The VAS, ASES score, and Constant-Murley score improved significantly in the in situ repair group (5.17 ± 2.00 points to 0.11 ± 0.41 points, p = 0.001; 44.04 ± 17.40 points to 95.47 ± 4.32 points, p = 0.001; 49.50 ± 14.38 points to 93.50 ± 3.49 points, p = 0.001) and in the tear completion before repair group (5.43 ± 3.32 points to 0.03 ± 0.18 points, p = 0.001; 41.50 ± 19.59 points to 95.94 ± 2.68 points, p = 0.001; 47.54 ± 17.13 points to 93.97 ± 2.61 points, p = 0.001). Postoperative MRI revealed that the re-tear rate was 7.1% (2/28) in the in situ repair group and 3.3% (1/30) in the tear completion before repair group. No significant differences were observed in terms of the functional scores, the percentages of patients achieving the MCID of the functional scores, and the re-tear rate between the two groups (p > 0.05).

CONCLUSIONS: Both in situ repair and tear completion before repair yielded satisfactory clinical outcomes for patients with bursal-side PTRCTs. No significant differences were observed in the functional and MRI outcomes between the two groups.

PMID:36864555 | DOI:10.1111/os.13693

Cereb Cortex. 2023 Mar 1:bhad030. doi: 10.1093/cercor/bhad030. Online ahead of print.

ABSTRACT

Schizophrenia is associated with a high prevalence of cigarette smoking. Neural dynamics are spatially structured and shaped by both microscale molecular and macroscale functional architectures, which are disturbed in the diseased brain. The neural mechanism underlying the schizophrenia-nicotine dependence comorbidity remains unknown. In this study, we aimed to test whether there is an interaction between schizophrenia and smoking in brain neural dynamics, and how the main effect of the 2 factors related to the molecular architecture. Functional magnetic resonance imaging data were obtained from 4 groups: schizophrenia and healthy controls with/without smoking. We identified 2 dynamics gradients combined with over 5,000 statistical features of the brain region’s time series. The interaction effect was found in the high-order functional network, and the main effect of schizophrenia was in the bilateral orbitofrontal cortices. Moreover, the disease- and smoking-related alteration in brain pattern was associated with spatial distribution of serotonin, cannabinoid, and glutamate. Collectively, these findings supported the self-medication hypothesis in schizophrenia-nicotine dependence with a neural intrinsic dynamics perspective.

PMID:36864548 | DOI:10.1093/cercor/bhad030