Nevin Manimala

J Clin Endocrinol Metab. 2023 Nov 15:dgad670. doi: 10.1210/clinem/dgad670. Online ahead of print.

ABSTRACT

CONTEXT: Few meta-analyses regarding the incidence of endocrine immune related adverse effects (eirAEs) have been published and many trials were published thereafter.

OBJECTIVE: To assess the risk and incidence of eirAEs of any grade and grade 3-5 by immune checkpoint inhibitor (ICI) mono or combination-therapy in solid tumors current literature was updated in this comprehensive meta-analysis.

METHODS: An electronic search using PubMed/Medline, Embase and the Cochrane Library was performed. Randomized controlled studies (RCT) assessing eirAEs under ICI-mono or ICI-combination therapy were selected. Stata software version 17 was used for statistical analyses and risk of bias was evaluated by using Review Manager version 5.3.

RESULTS: 69 RCTs with 80 independent reports, involving 42,886 patients were included in the study. Meta-analysis revealed the following pooled estimates for the risk ratio and the incidence, respectively: for any grade hypothyroidism 7.81 (95% CI, 5.68-10.74, p< 0.0001) and 7.64% (95% CI, 6.23-9.17, p< 0.0001); significantly increased also for hyperthyroidism, hypophysitis/hypopituitarism and adrenal insufficiency; and for insulin-dependent diabetes mellitus 1.52 (95% CI, 1.07-2.18, p= 0.02), and 0.087% (95% CI, 0.019-0.189, p= 0.0006), respectively. Meta-regression showed that combination of ICIs (nivolumab plus ipilimumab and durvalumab plus tremelimumab, respectively) is an independent risk factor for any grade hypophysitis/hypopituitarism, and that ICI agent is an independent factor of risk for adrenal insufficiency, but that cancer type is not an independent risk factor for eirAEs.

CONCLUSION: We showed that risk, independent from cancer type, and incidence of eAEs are substantially increased under ICI therapy. Combination of ICIs is increasing the risk for eirAEs, in particular for hypophysitis/hypopituitarism.

PMID:37967245 | DOI:10.1210/clinem/dgad670

J Clin Endocrinol Metab. 2023 Nov 15:dgad664. doi: 10.1210/clinem/dgad664. Online ahead of print.

ABSTRACT

CONTEXT: Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis.

OBJECTIVE: To group PCOS GWAS loci into genetic clusters associated with disease pathophysiology.

DESIGN/SETTING/PATIENTS OR OTHER PARTICIPANTS: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N=62,252). Associations with clinical outcomes (type 2 diabetes/T2D, coronary artery disease/CAD and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N=898,130, CARDIOGRAM/UKBB, N=547,261) and individual-level pPS in MGBB.

INTERVENTIONS/MAIN OUTCOME MEASURES/RESULTS: Four PCOS genetic clusters were identified with top loci indicated as following: (i) Cluster 1/Obesity/insulin resistance (FTO); (ii) Cluster 2/Hormonal/menstrual cycle changes (FSHB); (iii) Cluster 3/Blood markers/inflammation (ATXN2/SH2B3); (iv) Cluster 4/Metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (BMI; p=6.6×10-29); Cluster 2 with increased age of menarche (p= p=1.5×10-4); Cluster 3 with multiple decreased blood markers, including mean platelet volume (MPV; p=3.1 x10-5); and Cluster 4 with increased ALP (p=0.007). PCOS genetic clusters GWAS-pPS’s were also associated with disease outcomes: Cluster 1 pPS with increased T2D (OR 1.07; p=7.3×10-50), with replication in MGBB all participants (OR 1.09, p=2.7×10-7) and females only (OR 1.11, 4.8×10-5).

CONCLUSIONS: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes.

PMID:37967238 | DOI:10.1210/clinem/dgad664

Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2317870120. doi: 10.1073/pnas.2317870120. Epub 2023 Nov 15.

NO ABSTRACT

PMID:37967219 | DOI:10.1073/pnas.2317870120

Ann Med. 2023;55(2):2274511. doi: 10.1080/07853890.2023.2274511. Epub 2023 Nov 15.

ABSTRACT

INTRODUCTION: At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19.

METHODS: RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, molnupiravir, paxlovid, VV116, and placebo). The Cochrane risk of bias tool for randomized trials (RoB) was used to assess the bias risk of the included studies. The direct and indirect evidence were combined using a Bayesian network meta-analysis (PROSPERO Code No: CRD42023397837).

RESULTS: Direct analysis showed that paxlovid was associated with a reduced risk of mortality (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.06-0.25) and hospitalization (OR = 0.04, 95% CI: 0.00-0.67) compared with placebo. Network meta-analysis showed that paxlovid had the highest probability of being the best management strategy in patients with COVID-19, reducing mortality (OR = 0.11, 95% CI: 0.01-1.99; surface under the cumulative ranking curve [SUCRA]: 0.77) and hospitalization (OR = 0.06, 95% CI: 0.00-1.03; SUCRA: 0.95). For prespecified safety outcomes, SUCRA values ranked VV116 (OR = 0.09, 95% CI: 0.00-2.07: SUCRA 0.86) as the most beneficial intervention for the prevention of serious adverse events.

CONCLUSIONS: When compared to other antiviral medications, paxlovid can reduce the mortality and hospitalization of COVID-19 patients.

PMID:37967171 | DOI:10.1080/07853890.2023.2274511

PLoS One. 2023 Nov 15;18(11):e0294441. doi: 10.1371/journal.pone.0294441. eCollection 2023.

ABSTRACT

OBJECTIVE: Crohn’s disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy.

MATERIAL AND METHODS: A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy.

RESULTS: Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn’s Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test).

CONCLUSIONS: This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

PMID:37967139 | DOI:10.1371/journal.pone.0294441

PLoS One. 2023 Nov 15;18(11):e0292275. doi: 10.1371/journal.pone.0292275. eCollection 2023.

ABSTRACT

Reliable identification of plant species in the digestive tract of a deceased animal often represents the major key to diagnose a lethal intoxication with poisonous plants in veterinary pathology. In many cases, identification of the species is challenging or even impossible because the diagnostic morphological features have been degraded, and because the interpretation of such features requires a considerable expertise in plant anatomy and biodiversity. The use of DNA barcoding markers can support or even replace classical morphological assessment. While these markers have been widely used for plant taxonomy, their forensic application to clarify causes of animal poisoning is novel. In addition, we use specific single-nucleotide polymorphisms as fingerprints. This allows for a clear decision even in cases, where the conventionally used statistical e-values remain ambiguous. In the current work, we explore the feasibility of this strategy in a couple of exemplary cases, either in concert with anatomical diagnostics, or in cases where visual species identification is not possible, or where chemical toxin detection methods are not well established, complex, time consuming and expensive.

PMID:37967132 | DOI:10.1371/journal.pone.0292275

PLoS One. 2023 Nov 15;18(11):e0293541. doi: 10.1371/journal.pone.0293541. eCollection 2023.

ABSTRACT

Cultural translations of L1 and L2, in both directions, can indicate different behaviors of translators, influenced by the unique characteristics of each culture and the proficiency of the translator trainees’ bicultural competence. This study compares translator trainees’ behaviors when engaged in direct translation (L2 to L1) and inverse translation (L1 to L2) of cultural references to reveal the extent to which directionality influences trainees’ actual and perceived behaviors. Following a hypothesis-based observational design, the authors examine a single group’s behaviors under two conditions (direct translation and inverse translation), using Translog-II and a questionnaire. The data are analyzed quantitatively using the Wilcoxon test and descriptive statistics. The key findings indicate that inverse translation demands more cognitive effort than direct translation, particularly in online revision (n = 16, z = -3.206, p < .05) and production speed (n = 16, z = -3.068, p < .05). Conversely, direct translation requires more cognitive effort, especially in orientation time (n = 16, z = -2.482, p < .05) and performance (n = 16, z = -3.346, p < .05). Additionally, the students’ responses to the questionnaire reveal a tendency to rely more on online resources than on internal translation strategies. The authors suggest that translation students should receive training in both translation directions, effective management of the translation process, appropriate utilization of translation strategies, and cultural competence. These components should be integrated into translation training courses and instructional methods.

PMID:37967125 | DOI:10.1371/journal.pone.0293541

PLoS One. 2023 Nov 15;18(11):e0292403. doi: 10.1371/journal.pone.0292403. eCollection 2023.

ABSTRACT

Social media is emerged as a powerful communication tool over the past ten years. The Z generation’s green buying habits and purchase intentions are being reshaped by social media, which is helping to advance the development of a sustainable environment. The consumption of non-organic products has raised carbon emissions, so changing consumption patterns and purchase intentions is necessary for a more sustainable future. Moreover, earlier literature has the absence of a comprehensive behavior change model that explains the mechanism through which social media influences sustainable behaviors This study explores that how social media affects patterns of consumption for Z generation of China while considering the role of environmental concerns, subjective norms, eco-branding and eco-labeling on the basis of theory of planned behavior. A questionnaire is used to get information from the 563 Z generation respondents of China. The data is analyzed using Smart-PLS and empirical outcomes show that social media has a statistically significant influence on shaping and affecting green consumption behavior of China’s Z generation because it has the potential to reach a vast audience and spread awareness about environmental issues, leading to increased intention towards a sustainable environment and reduction in carbon emissions. It also provides a platform for individuals to express their opinions and engage in discussions on environmental issues. These developments are promising for the future of environmental sustainability as they indicate a growing interest in preserving the planet among the Z generation of China. It can be recommended as a policy tool that government and other organizations should support the development of informative content on social media platforms, highlighting the importance of environmental sustainability and eco-friendly habits.

PMID:37967117 | DOI:10.1371/journal.pone.0292403

PLoS One. 2023 Nov 15;18(11):e0289289. doi: 10.1371/journal.pone.0289289. eCollection 2023.

ABSTRACT

INTRODUCTION: The healthy plate model (HPM) is a practical guide to modulate the portion of staple food in main meals, subsequently affecting the risks associated with Non-communicable Diseases include type2 diabetes mellitus (T2DM).

OBJECTIVE: This study investigated the effectiveness of health information and the healthy plate model on cardio-metabolic risk factors, knowledge and attitude towards T2DM prevention measures.

METHODS: A pre-post analysis, as part of a cluster randomized trial with street food vendors and their customers, was implemented in three randomly selected districts in Dar es Salaam, Tanzania. Two vendor-customer clusters each with 15 and more vendors from each district were randomly assigned to receive either T2DM health information only (Intervention package1 [IP1]) or IP1 plus a subsidized meal with vegetables and fruits, following the principles of the HPM (Intervention package2 [IP2]). Within the clusters the participants were informed on the importance of the intervention they received. An intervention period lasted for three months from 1st April to 31st June 2019. We applied Generalized Linear Mixed Models and Bayesian Modelling (for sensitivity analysis) to assess the effectiveness of the interventions.

RESULTS: Overall, 336 (IP2 = 175 and IP1 = 161) out of 560 (280/arm) previous study participants participated in evaluation. Diastolic BP was lower among IP2 participants in the evaluation than baseline AβC = -4.1mmHg (95%CI:-5.42 to -2.76). After adjusting for the interaction between IP2 and age of the consumers, the BMI was significantly lower among IP2 in the evaluation than baseline AβC = -0.7kg/m2 (95%CI: -1.17 to -0.23). With interaction between IP2 and income, BMI was higher in the IP2 in the evaluation than baseline AβC = 0.73kg/m2 (95%CI: 0.08 to 1.38). Systolic and diastolic BP were significantly lower among IP1 in the evaluation than baseline AβC = -3.5mmHg (95%CI:-5.78 to -1.24) and AβC = -5.9mmHg (95%CI:-7.34 to -4.44) respectively. Both the knowledge scores and positive attitudes towards T2DM prevention measures were higher in the evaluation than baseline in both interventions arms.

CONCLUSION: The positive effects on cardio-metabolic risk factors, knowledge and attitude were observed in both intervention arms. Due to interactions between IP2, age and income; designing interventions relating to food and cardio-metabolic risk factors, should consider combining socio-economic factors.

PMID:37967111 | DOI:10.1371/journal.pone.0289289

PLoS One. 2023 Nov 15;18(11):e0291394. doi: 10.1371/journal.pone.0291394. eCollection 2023.

ABSTRACT

BACKGROUND: Homebirth preference is the intention/plan to give birth outside health facilities with the help of unskilled birth attendants. The preference to give birth at home without a skilled birth attendant leads to care-seeking delays, intrapartum mortality, multiple stillbirths, and postpartum morbidities and mortality. Therefore, this study aimed to estimate the pooled prevalence of homebirth preference and associated factors among pregnant women in Ethiopia.

METHODS: Search of Google Scholar, Medline, PubMed, Cochrane Library and Web of Science were done for this study from 20th August 2022 to 6th November 2022. For data extraction and analysis, the standardized data extraction checklist and Stata version 14 were used respectively. Sentence as “Cochrane Q test statistics and I2 statistics were used to check heterogeneity of the studies. The pooled prevalence of homebirth preference was estimated using a random-effects model. The association between homebirth preference and independent variables was determined using an odd ratio with a 95% confidence interval. A funnel plot and Egger’s test were used to assess publication bias.

RESULTS: A total of 976 research articles were identified. Seven studies that fulfilled eligibility criteria were included in this systematic review and meta-analysis. The pooled prevalence of homebirth preference in Ethiopia was 39.62% (95% CI 27.98, 51.26). The current meta-analysis revealed that average monthly income <1800 ETB (OR = 2.66, 95% CI 1.44, 4.90) lack of ANC follow-up (OR = 2.57, 95%CI 1.32, 5.01), being multipara (OR = 1.77, 95%CI 1.39, 2.25), poor knowledge about obstetric danger sign (OR = 5.75, 95%CI 1.o2, 32.42), and not discussing the place of delivery with a partner (OR = 5.89 (95%CI 1.1, 31.63) were significantly associated with homebirth preference.

CONCLUSION: This systematic review and meta-analysis examined the substantial prevalence of homebirth preference in Ethiopia which may contribute maternal and child health crisis. The homebirth preference was associated with low average monthly income (<1800 ETB), lack of ANC follow-up, multipara, poor knowledge about obstetric danger signs, and not discussing with their partner the place of delivery. Improving knowledge of pregnant women about the benefit of health facility delivery and obstetric danger signs is necessary to decrease the prevalence of homebirth preference; for these can reduce negative outcomes occurred during delivery.

PMID:37967092 | DOI:10.1371/journal.pone.0291394