Nevin Manimala

J Immunother Cancer. 2021 Mar;9(3):e001458. doi: 10.1136/jitc-2020-001458.

ABSTRACT

BACKGROUND: Some sarcomas respond to immune checkpoint inhibition, but predictive biomarkers are unknown. We analyzed tumor DNA methylation profiles in relation to immunological parameters and response to anti-programmed cell death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy in patients with sarcoma.

PATIENTS AND METHODS: We retrospectively identified adult patients who had received anti-PD-1 ICI therapy for recurrent sarcoma in two independent centers. We performed (1) blinded radiological response evaluation according to immune response evaluation criteria in solid tumors (iRECIST) ; (2) tumor DNA methylation profiling of >850,000 probes using Infinium MethylationEPIC microarrays; (3) analysis of tumor-infiltrating immune cell subsets (CD3, CD8, CD45RO, FOXP3) and intratumoral expression of immune checkpoint molecules (PD-L1, PD-1, LAG-3) using immunohistochemistry; and (4) evaluation of blood-based systemic inflammation scores (neutrophil-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio). Response to anti-PD-1 ICI therapy was bioinformatically and statistically correlated with DNA methylation profiles and immunological data.

RESULTS: 35 patients (median age of 50 (23-81) years; 18 females, 17 males; 27 soft tissue sarcomas; 8 osteosarcomas) were included in this study. The objective response rate to anti-PD-1 ICI therapy was 22.9% with complete responses in 3 out of 35 and partial responses in 5 out of 35 patients. Adjustment of DNA methylation data for tumor-infiltrating immune cells resulted in identification of methylation differences between responders and non-responders to anti-PD-1 ICI. 2453 differentially methylated CpG sites (DMPs; 2043 with decreased and 410 with increased methylation) were identified. Clustering of sarcoma samples based on these DMPs revealed two main clusters: methylation cluster 1 (MC1) consisted of 73% responders and methylation cluster 2 (MC2) contained only non-responders to anti-PD-1 ICI. Median progression-free survival from anti-PD-1 therapy start of MC1 and MC2 patients was 16.5 and 1.9 months, respectively (p=0.001). Median overall survival of these patients was 34.4 and 8.0 months, respectively (p=0.029). The most prominent DNA methylation differences were found in pathways implicated in Rap1 signaling, focal adhesion, adherens junction Phosphoinositide 3-kinase (PI3K)-Akt signaling and extracellular matrix (ECM)-receptor interaction.

CONCLUSIONS: Our data demonstrate that tumor DNA methylation profiles may serve as a predictive marker for response to anti-PD-1 ICI therapy in sarcoma.

PMID:33762319 | DOI:10.1136/jitc-2020-001458

Ann Rheum Dis. 2021 Mar 24:annrheumdis-2021-220332. doi: 10.1136/annrheumdis-2021-220332. Online ahead of print.

NO ABSTRACT

PMID:33762266 | DOI:10.1136/annrheumdis-2021-220332

Ann Rheum Dis. 2021 Mar 24:annrheumdis-2021-220336. doi: 10.1136/annrheumdis-2021-220336. Online ahead of print.

NO ABSTRACT

PMID:33762265 | DOI:10.1136/annrheumdis-2021-220336

BMJ. 2021 Mar 24;372:n532. doi: 10.1136/bmj.n532.

ABSTRACT

OBJECTIVE: To describe the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia who experience depression as a neuropsychiatric symptom of dementia or have a diagnosis of a major depressive disorder.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline, Embase, the Cochrane Library, CINAHL, PsycINFO, and grey literature between inception and 15 October 2020.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised trials comparing drug or non-drug interventions with usual care or any other intervention targeting symptoms of depression in people with dementia.

MAIN OUTCOME MEASURES: Pairs of reviewers screened studies, abstracted aggregate level data, and appraised risk of bias with the Cochrane risk of bias tool, which facilitated the derivation of standardised mean differences and back transformed mean differences (on the Cornell scale for depression in dementia) from bayesian random effects network meta-analyses and pairwise meta-analyses.

RESULTS: Of 22 138 citations screened, 256 studies (28 483 people with dementia) were included. Missing data posed the greatest risk to review findings. In the network meta-analysis of studies including people with dementia without a diagnosis of a major depressive disorder who were experiencing symptoms of depression (213 studies; 25 177 people with dementia; between study variance 0.23), seven interventions were associated with a greater reduction in symptoms of depression compared with usual care: cognitive stimulation (mean difference -2.93, 95% credible interval -4.35 to -1.52), cognitive stimulation combined with a cholinesterase inhibitor (-11.39, -18.38 to -3.93), massage and touch therapy (-9.03, -12.28 to -5.88), multidisciplinary care (-1.98, -3.80 to -0.16), occupational therapy (-2.59, -4.70 to -0.40), exercise combined with social interaction and cognitive stimulation (-12.37, -19.01 to -5.36), and reminiscence therapy (-2.30, -3.68 to -0.93). Except for massage and touch therapy, cognitive stimulation combined with a cholinesterase inhibitor, and cognitive stimulation combined with exercise and social interaction, which were more efficacious than some drug interventions, no statistically significant difference was found in the comparative efficacy of drug and non-drug interventions for reducing symptoms of depression in people with dementia without a diagnosis of a major depressive disorder. Clinical and methodological heterogeneity precluded network meta-analysis of studies comparing the efficacy of interventions specifically for reducing symptoms of depression in people with dementia and a major depressive disorder (22 studies; 1829 patients).

CONCLUSIONS: In this systematic review, non-drug interventions were found to be more efficacious than drug interventions for reducing symptoms of depression in people with dementia without a major depressive disorder.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017050130.

PMID:33762262 | DOI:10.1136/bmj.n532

Int J Biostat. 2021 Mar 24. doi: 10.1515/ijb-2020-0091. Online ahead of print.

ABSTRACT

The receiver operating-characteristic (ROC) curve is a well-known graphical tool routinely used for evaluating the discriminatory ability of continuous markers, referring to a binary characteristic. The area under the curve (AUC) has been proposed as a summarized accuracy index. Higher values of the marker are usually associated with higher probabilities of having the characteristic under study. However, there are other situations where both, higher and lower marker scores, are associated with a positive result. The generalized ROC (gROC) curve has been proposed as a proper extension of the ROC curve to fit these situations. Of course, the corresponding area under the gROC curve, gAUC, has also been introduced as a global measure of the classification capacity. In this paper, we study in deep the gAUC properties. The weak convergence of its empirical estimator is provided while deriving an explicit and useful expression for the asymptotic variance. We also obtain the expression for the asymptotic covariance of related gAUCs and propose a non-parametric procedure to compare them. The finite-samples behavior is studied through Monte Carlo simulations under different scenarios, presenting a real-world problem in order to illustrate its practical application. The R code functions implementing the procedures are provided as Supplementary Material.

PMID:33761578 | DOI:10.1515/ijb-2020-0091

Laryngorhinootologie. 2021 Mar 24. doi: 10.1055/a-1430-7735. Online ahead of print.

ABSTRACT

INTRODUCTION: The SARS-CoV-2 pandemic has led to profound limitations in patient care and student teaching at the University Hospitals of Otorhinolaryngology (ORL). In contrast, the impact on research has been variable. To classify the pandemic-related effect on research, the development of the number of scientific publications of the German ORL university hospitals before and during the pandemic was analyzed.

MATERIAL AND METHODS: The publication performance between 2015 and 2020 of the 39 current chairmen was surveyed using a literature search (Pubmed). All entries relating to the chairmen of the university hospital as first, last or co-author were included. The absolute and relative development of each author’s publication performance was determined and evaluated using nonparametric statistical methods.

RESULTS: A total of 2420 publications could be documented. From 2015 to 2019, an average of 368 publications were published per year. In 2020, this number increased by 57.9 % to 581 publications. While the number of monthly publications remained constant between 2015 and 2019, a significant increase was seen from May 2020 up to a maximum of 74 publications in September 2020. In 2020, 34 articles (5.9 %) had a thematic relation to the SARS-CoV-2 pandemic, with 7 of these papers (20.6 %) resulting from cross-site publications.

CONCLUSION: In 2020, the number of scientific publications was raised to more than 1.5 times the usual annual publications. This increase was clearly related in time to the reduction of elective patient care during the SARS-CoV-2 pandemic starting in mid-March 2020. Probably, free time capacities enabled this increased publication output. Our results confirm the great scientific potential of the ORL university hospitals, which has been successfully implemented despite the pandemic.

PMID:33761572 | DOI:10.1055/a-1430-7735

Homeopathy. 2021 Mar 24. doi: 10.1055/s-0040-1722232. Online ahead of print.

ABSTRACT

BACKGROUND: Though frequently used in practice, research studies have shown inconclusive benefits of homeopathy in the treatment of warts. We aimed to assess the feasibility of a future definitive trial, with preliminary assessment of differences between effects of individualized homeopathic (IH) medicines and placebos in treatment of cutaneous warts.

METHODS: A double-blind, randomized, placebo-controlled trial (n = 60) was conducted at the dermatology outpatient department of D.N. De Homoeopathic Medical College and Hospital, West Bengal. Patients were randomized to receive either IH (n = 30) or identical-looking placebo (n = 30). Primary outcome measures were numbers and sizes of the warts; secondary outcome was the Dermatology Life Quality Index (DLQI) questionnaire measured at baseline, and every month up to 3 months. Group differences and effect sizes were calculated on the intention-to-treat sample.

RESULTS: Attrition rate was 11.6% (IH, 3; placebo, 4). Intra-group changes were significantly greater (all p < 0.05, Friedman tests) in IH than placebo. Inter-group differences were statistically non-significant (all p > 0.05, Mann-Whitney U tests) with small effect sizes-both in the primary outcomes (number of warts after 3 months: IH median [inter-quartile range; IQR] 1 [1, 3] vs. placebo 1 [1, 2]; p = 0.741; size of warts after 3 months: IH 5.6 mm [2.6, 40.2] vs. placebo 6.3 [0.8, 16.7]; p = 0.515) and in the secondary outcomes (DLQI total after 3 months: IH 4.5 [2, 6.2] vs. placebo 4.5 [2.5, 8]; p = 0.935). Thuja occidentalis (28.3%), Natrum muriaticum (10%) and Sulphur (8.3%) were the most frequently prescribed medicines. No harms, homeopathic aggravations, or serious adverse events were reported.

CONCLUSION: As regards efficacy, the preliminary study was inconclusive, with a statistically non-significant direction of effect favoring homeopathy. The trial succeeded in showing that an adequately powered definitive trial is both feasible and warranted.

TRIAL REGISTRATION: CTRI/2019/10/021659; UTN: U1111-1241-7340.

PMID:33761570 | DOI:10.1055/s-0040-1722232

Gesundheitswesen. 2021 Mar 24. doi: 10.1055/a-1388-7203. Online ahead of print.

ABSTRACT

BACKGROUND: There are only limited data on the extent to which children and adolescents with the need of integrative assistance (KiJu-PflEh) are considered for outreach dental care service. Aim The aim of this study was to evaluate accounting data from the Kassenzahnärztliche Bundesvereinigung (KZBV) on the use of dental care by KiJU-PflEh. Material and Methods Based on six specific BEMA items (accounting year 2019), the KZBV performed a filtering of GKV-insured persons (0-17 years). The generated data sets of the study group (KiJu-PflEh) and the control group (all KiJu) were made the UW/H available in anonymized form for further analyses.

RESULTS: The study group comprised 1602 KiJu-PflEh (mean age: 11.6 years). The gender ratio from ♂ to ♀ was 2:1. 56.0% of the KiJu-PflEh underwent diagnostic dental examination. The use of individual prophylactic (IP) measures was as follows: oral hygiene status assessment – IP1 (47.5%), oral health promotion – IP2 (46.1%), fluoridation of the teeth – IP4 (63.1%), fissure sealing per tooth – IP5 (30.1%). Compared to KiJu, statistically significantly fewer IP-measures were taken and carried out in the study group KiJu-PflEh. (KiJu: 85.7%; KiJu-PflEh: 46.7%).

CONCLUSION: For the first time, it was shown that KiJu-PflEh is inadequately cared for and provided with dental care in comparison to peers in the general population. Increased dental care is urgently recommended as the KiJu-PflEh group has a high risk of caries. Medical information is also necessary to implement targeted prevention measures for all KiJu-PflEh. For this purpose, the introduction of a central database, which enables dental and general medical networking, should be driven forward. Furthermore, there is a need for more research to obtain primary data on the epidemiology of caries in KiJu-PflEh to verify the findings of the present pilot study.

PMID:33761559 | DOI:10.1055/a-1388-7203

Gesundheitswesen. 2021 Mar 24. doi: 10.1055/a-1330-7267. Online ahead of print.

ABSTRACT

HINTERGRUND: Das Projekt “Gesunde Südstadt” hat den Schwerpunkt Gesundheitsförderung in der Lebenswelt Kommune. Es wurde im Rahmen des “Präventionsgesetzes” (SGB V §20a) initiiert und zielt ab auf die Verringerung der gesundheitlichen Ungleichheit in der Stadt Nürnberg. Die Maßnahmen der kommunalen Gesundheitsförderung im Handlungsfeld Ernährung wurden durch eine externe multiperspektivische, multimethodische Prozess- und Ergebnisevaluation begleitend untersucht.

METHODEN: 55 Maßnahmenberichte, 8 Interviews mit Teilnehmenden sowie 3 Interviews mit Maßnahmendurchführenden wurden mit qualitativer Inhaltsanalyse ausgewertet. Eine Teilnehmendenbefragung (n=35) mittels Fragebögen wurde quantitativ-statistisch ausgewertet.

ERGEBNISSE: Die Ergebnisse zeigen, dass die Gesundheitsförderungsmaßnahmen durch die Teilnehmenden eine hohe Akzeptanz erfuhren und ein ausgeprägtes Maß an Partizipation ermöglicht wurde. Weiterhin zeigen die Ergebnisse, dass die Maßnahmen die interaktive sowie die funktionale Gesundheitskompetenz förderten. Ein empirisches Pfadmodell für kommunale Gesundheitsförderungsprojekte wurde abgeleitet.

SCHLUSSFOLGERUNG: Die Ergebnisse belegen gesundheitsförderliche Effekte eines verhältnis- und verhaltensbasierten, kommunalen Ansatzes zur Gesundheitsförderung bei Teilnehmenden an Maßnahmen im Handlungsfeld Ernährung. Das Projekt “Gesunde Südstadt” stellt einen systematischen, lebensweltrelevanten und niedrigschwelligen Ansatz der soziallagenbezogenen Gesundheitsförderung im kommunalen Setting dar. Methodische Einschränkungen, wie das Querschnittsdesign der Studie, werden diskutiert.

BACKGROUND AND OBJECTIVES: The Project “Gesunde Südstadt” is focused on community-based health promotion interventions. It was initiated as part of the “Prevention Act” (SGB V §20a) and aims to reduce health inequalities in the city of Nuremberg. The community-based health promotion interventions focussing on nutrition were evaluated with an external multi-perspective, multi-method evaluation approach with a focus both on process and outcome results.

METHODS: 55 reports on activities, 8 interviews with participants and 3 interviews with trainers were coded using qualitative content analysis. Statistical analyses were conducted on a participant survey (n=35).

RESULTS: Results showed that the community-based health promotion interventions were not only widely accepted by the participants but also enabled them to participate in health-related activities. Additionally, health promotion interventions in the community were found to promote interactive and functional health competences. An empirically derived path model for community-based health promotion interventions was statistically tested.

CONCLUSIONS: Results show health promotion effects of community-based nutrition-related health promotion interventions on participants. The project “Gesunde Südstadt” thus represents a systematic, relevant and low-threshold approach to health promotion in a communal setting. Methodological limitations such as the cross-sectional design are discussed.

PMID:33761558 | DOI:10.1055/a-1330-7267

Gesundheitswesen. 2021 Mar 24. doi: 10.1055/a-1378-8859. Online ahead of print.

ABSTRACT

AIM OF THE STUDY: Taking into consideration and addressing patients’ psychosocial problems is one of the characteristics of good clinical practice; this applies to IBD-patients as well. Since 2014, such patients have been offered an online questionnaire-based problem assessment linked to care recommendations. The primary aim of our data analysis was to carry out a comparative description of socio-demographic and disease-related characteristics of users of the free service.

METHODOLOGY: For a retrospective data analysis, the online sample (OG) comprising 2156 CD and UC patients was compared with 852 individuals who participated in 2 IBD health services research studies (CG). Besides descriptive statistics, regression and covariance analyses were carried out.

RESULTS: The OG differed from CG in a highly significant and partly clinically relevant way. One in 3 of the OG was younger than 30 years of age (CG: 19%); 45% had completed high school (CG: 36%). In the OG, fewer were in disease remission (OG 34%; CG 59%). Even controlling for these differences, the OG reported more often greater burden in 12 of 17 psychosocial problem areas and expressed a greater need for information on 5 of 9 disease-related topic areas.

CONCLUSION: The internet-based assessment of psychosocial problems is used primarily by younger, better educated, and physically as well as psychosocially more burdened IBD patients with comparatively high information needs. The assessment may help them to actively participate in their care. Our data sheds further light on the peculiarities of internet-based study groups.

PMID:33761557 | DOI:10.1055/a-1378-8859