Category: Nevin Manimala

Genome Med. 2023 Dec 4;15(1):108. doi: 10.1186/s13073-023-01263-7.

ABSTRACT

BACKGROUND: In vitro and in vivo studies have shown that certain cytokines and hormones may play a role in the development and progression of type 2 diabetes (T2D). However, studies on their role in T2D in humans are scarce. We evaluated associations between 11 circulating cytokines and hormones with T2D among a population of sub-Saharan Africans and tested for causal relationships using Mendelian randomization (MR) analyses.

METHODS: We used logistic regression analysis adjusted for age, sex, body mass index, and recruitment country to regress levels of 11 cytokines and hormones (adipsin, leptin, visfatin, PAI-1, GIP, GLP-1, ghrelin, resistin, IL-6, IL-10, IL-1RA) on T2D among Ghanaians, Nigerians, and Kenyans from the Africa America Diabetes Mellitus study including 2276 individuals with T2D and 2790 non-T2D individuals. Similar linear regression models were fitted with homeostatic modelling assessments of insulin sensitivity (HOMA-S) and β-cell function (HOMA-B) as dependent variables among non-T2D individuals (n = 2790). We used 35 genetic variants previously associated with at least one of these 11 cytokines and hormones among non-T2D individuals as instrumental variables in univariable and multivariable MR analyses. Statistical significance was set at 0.0045 (0.05/11 cytokines and hormones).

RESULTS: Circulating GIP and IL-1RA levels were associated with T2D. Nine of the 11 cytokines and hormones (exceptions GLP-1 and IL-6) were associated with HOMA-S, HOMA-B, or both among non-T2D individuals. Two-stage least squares MR analysis provided evidence for a causal effect of GIP and IL-RA on HOMA-S and HOMA-B in multivariable analyses (GIP ~ HOMA-S β = – 0.67, P-value = 1.88 × 10^-6 and HOMA-B β = 0.59, P-value = 1.88 × 10^-5; IL-1RA ~ HOMA-S β = – 0.51, P-value = 8.49 × 10^-5 and HOMA-B β = 0.48, P-value = 5.71 × 10^-4). IL-RA was partly mediated via BMI (30-34%), but GIP was not. Inverse variance weighted MR analysis provided evidence for a causal effect of adipsin on T2D (multivariable OR = 1.83, P-value = 9.79 × 10^-6), though these associations were not consistent in all sensitivity analyses.

CONCLUSIONS: The findings of this comprehensive MR analysis indicate that circulating GIP and IL-1RA levels are causal for reduced insulin sensitivity and increased β-cell function. GIP’s effect being independent of BMI suggests that circulating levels of GIP could be a promising early biomarker for T2D risk. Our MR analyses do not provide conclusive evidence for a causal role of other circulating cytokines in T2D among sub-Saharan Africans.

PMID:38049854 | DOI:10.1186/s13073-023-01263-7

BMC Health Serv Res. 2023 Dec 4;23(1):1350. doi: 10.1186/s12913-023-10319-8.

ABSTRACT

BACKGROUND: Discarding pharmaceuticals in the garbage or into the sewage system are still the most common methods in many countries. This study aims to investigate the guidance provided by pharmacists to customers on the disposal of unused and expired household medications in São Paulo State, Brazil.

METHOD: The study population consisted of 630 pharmacists from the State of São Paulo, who work in community pharmacies. They answered an online questionnaire with questions composed in three blocks: demographic, work, and academic information on the pharmacist; guidance about the disposal of household medications; and knowledge regarding the reverse logistics of these medications. An invitation to participate in the questionnaire was made via WhatsApp, individually and collectively. Inferential statistics were performed using the chi-square test and were considered significant when p < 0.05%.

RESULTS: Among the participating pharmacists, the majority were women under 60 years old,56 (8.89%) stated that they never orient the customer regarding the disposal of unused and expired household medications, while 574 (91,12%) indicated that they almost provide guidance. The frequency with which they provided guidance was influenced by the number of years since graduation (p = 0.0047), the time they had worked in pharmacies and drugstores (p = 0.0007), and whether or not they had a graduate degree (p = 0.0181). Regarding the disposal of medications, among the 643 responses provided by the pharmacists,516 (80.25%) indicated that they oriented customers to return them to a pharmacy.

CONCLUSION: A small number of pharmacists always orient customers on the proper disposal that should be followed for unused and expired household medications, prioritizing their return to a pharmacy. In general, these pharmacists have longer periods of work experience and higher academic qualifications. Thus, it is important to increase knowledge through professional training and further education programs.

PMID:38049849 | DOI:10.1186/s12913-023-10319-8

Malar J. 2023 Dec 5;22(1):370. doi: 10.1186/s12936-023-04805-x.

ABSTRACT

BACKGROUND: Malaria is one of the most prominent illnesses affecting children, ranking as one of the key development concerns for many low- and middle-income countries (LMICs). There is not much information available on the use of anti-malarial drugs in LMICs in children under five. The study aimed to investigate disparities in anti-malarial drug consumption for malaria among children under the age of five in LMICs.

METHODS: This study used recent available cross-sectional data from the Malaria Indicator Survey (MIS) datasets across five LMICs (Guinea, Kenya, Mali, Nigeria, and Sierra Leone), which covered a portion of sub-Saharan Africa. The study was carried out between January 2, 2023, and April 15, 2023, and included children under the age of five who had taken an anti-malarial drug for malaria 2 weeks before the survey date. The outcome variable was anti-malarial drug consumption, which was classified into two groups: those who had taken anti-malarial drugs and those who had not.

RESULTS: In the study of LMICs, 32,397 children under five were observed, and among them, 44.1% had received anti-malarial drugs. Of the five LMICs, Kenya had the lowest (9.2%) and Mali had the highest (70.5%) percentages of anti-malarial drug consumption. Children under five with malaria are more likely to receive anti-malarial drugs if they are over 1 year old, live in rural areas, have mothers with higher education levels, and come from wealthier families.

CONCLUSION: The study emphasizes the importance of developing universal coverage strategies for anti-malarial drug consumption at both the national and local levels. The study also recommends that improving availability and access to anti-malarial drugs may be necessary, as the consumption of these drugs for treating malaria in children under the age of five is shockingly low in some LMICs.

PMID:38049847 | DOI:10.1186/s12936-023-04805-x

Eur J Med Res. 2023 Dec 4;28(1):560. doi: 10.1186/s40001-023-01530-8.

ABSTRACT

BACKGROUND: Survivors of critical illness are frequently left with a long-lasting disability. We hypothesised that patients who developed delirium during ICU stay, compared with patients who did not, would have worse health-related quality of life following a critical illness.

METHODS: Prospective longitudinal observational and analytical study assessing functional independence, frailty and perceived quality of life measured with the Barthel Index, the Clinical Frailty Scale, and the SF-36, comparing patients who developed delirium during ICU stay and patients who did not. The questionnaires were used at different times during the follow-up (upon ICU admission, at ICU discharge, at hospital discharge and 2 years after hospital discharge).

RESULTS: In a cohort of 1462 patients, we matched 93 patients who developed delirium (delirium group) with 93 patients who did not develop delirium (no-delirium group). Of 156 completed questionnaires (84.7%), we observed that (a) in each of the two groups of patients, the scores related to functional independence (Barthel Index) and frailty (Clinical Frailty Scale) tended to improve over time (p < 0.001), being consistently less favourable in the delirium group compared to the no-delirium group (p < 0.001); (b) the patients who developed delirium also presented lower scores on the SF-36 scale, these differences being statistically significant, and therefore evidencing a worse quality of life, with impact on both the psychological and social spheres (p < 0.001).

CONCLUSIONS: Patients who developed delirium had significantly lower scores 2 years after hospital discharge on the three used questionnaires, displaying a clear negative impact on the physical, psychological, and social dimensions. The study’s results reinforce the need to support and strengthen the care of ICU survivors.

PMID:38049839 | DOI:10.1186/s40001-023-01530-8

Patient Saf Surg. 2023 Dec 4;17(1):29. doi: 10.1186/s13037-023-00373-w.

ABSTRACT

BACKGROUND: Preoperative anemia is a common hematologic problem in major orthopedic surgery in developing countries. It is a condition in which the number and size of red blood cells are insufficient to meet the body’s physiologic needs, consequently impairing the capacity of the blood to transport oxygen to the body. Preoperative anemia is common in elective orthopedic surgical patients and is an independent risk factor for perioperative morbidity and mortality. This study aimed to assess preoperative anemia prevalence and risk factors in patients undergoing elective orthopedic procedures.

METHOD: A multicenter prospective observational cohort study was conducted from June 01 to August 30, 2022. A systematic random sampling technique was used to select the study unit. Data were collected using a structured questionnaire. Descriptive statistics were expressed in percentages and presented with tables and figures. Binary logistic regression was used to see the association between independent and dependent variables. A P-value < 0.05 was considered statistically significant.

RESULT: Preoperative anemia’s prevalence and risk factors in patients undergoing elective orthopedic procedures was 24.1[95%CI= (18.2-30.6)]. Multivariable logistic analyses showed that low monthly income level [AOR:5,95%CI:(1.36-7.98)], patient with cancer [AOR:3.4,95%CI:(3.7-8.84)], patient with malaria infectious [AOR: 3.2,95%CI:( 1.13-8.91)], patient with anti-retroviral therapy [AOR: 5.2,95%CI:( 1.8-11.04)], and previous history of surgery [AOR:1,95%CI(1.43-2.4)], were factors significantly associated with preoperative anemia.

CONCLUSION: The prevalence of preoperative anemia among adult patients who underwent elective orthopedics procedures was high. Low Monthly income, patients with cancer, patient with malaria infection, and patients with anti-retroviral therapy, previous histories of surgery were found significantly associated with preoperative anemia. So, we recommend to health professional’s early identification, diagnosis and treatment of preoperative anemia should be done to reduce the risks of anemia and related adverse outcomes.

PMID:38049835 | DOI:10.1186/s13037-023-00373-w

Trials. 2023 Dec 4;24(1):784. doi: 10.1186/s13063-023-07775-2.

ABSTRACT

BACKGROUND: Retention to trials is important to ensure the results of the trial are valid and reliable. The SPIRIT guidelines (18b) require “plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols” be included in trial protocols. It is unknown how often protocols report this retention information. The purpose of our scoping review is to establish if, and how, trial teams report plans for retention during the design stage of the trial.

MATERIALS AND METHODS: A scoping review with searches in key databases (PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science from 2014 to 2019 inclusive) to identify randomised controlled trial protocols. We produced descriptive statistics on the characteristics of the trial protocols and also on those adhering to SPIRIT item 18b. A narrative synthesis of the retention strategies was also conducted.

RESULTS: Eight-hundred and twenty-four protocols met our inclusion criteria. RCTs (n = 722) and pilot and feasibility trial protocols (n = 102) reported using the SPIRIT guidelines during protocol development 35% and 34.3% of the time respectively. Of these protocols, only 9.5% and 11.4% respectively reported all aspects of SPIRIT item 18b “plans to promote participant retention and to complete follow-up, including list of any outcome data for participants who discontinue or deviate from intervention protocols”. Of the RCT protocols, 36.8% included proactive “plans to promote participant retention” regardless of whether they reported using SPIRIT guidelines or not. Most protocols planned “combined strategies” (48.1%). Of these, the joint most commonly reported were “reminders and data collection location and method” and “reminders and monetary incentives”. The most popular individual retention strategy was “reminders” (14.7%) followed by “monetary incentives- conditional” (10.2%). Of the pilot and feasibility protocols, 40.2% included proactive “plans to promote participant retention” with the use of “combined strategies” being most frequent (46.3%). The use of “monetary incentives – conditional” (22%) was the most popular individual reported retention strategy.

CONCLUSION: There is a lack of reporting of plans to promote participant retention in trial protocols. Proactive planning of retention strategies during the trial design stage is preferable to the reactive implementation of retention strategies. Prospective retention planning and clear communication in protocols may inform more suitable choice, costing and implementation of retention strategies and improve transparency in trial conduct.

PMID:38049833 | DOI:10.1186/s13063-023-07775-2

BMC Med. 2023 Dec 5;21(1):485. doi: 10.1186/s12916-023-03197-8.

ABSTRACT

BACKGROUND: We aimed to investigate the protein pathways linking obesity and lifestyle factors to coronary artery disease (CAD).

METHODS: Summary-level genome-wide association statistics of CAD were obtained from the CARDIoGRAMplusC4D consortium (60,801 cases and 123,504 controls) and the FinnGen study (R8, 39,036 cases and 303,463 controls). Proteome-wide Mendelian randomization (MR) analysis was conducted to identify CAD-associated blood proteins, supplemented by colocalization analysis to minimize potential bias caused by linkage disequilibrium. Two-sample MR analyses were performed to assess the associations of genetically predicted four obesity measures and 13 lifestyle factors with CAD risk and CAD-associated proteins’ levels. A two-step network MR analysis was conducted to explore the mediating effects of proteins in the associations between these modifiable factors and CAD.

RESULTS: Genetically predicted levels of 41 circulating proteins were associated with CAD, and 17 of them were supported by medium to high colocalization evidence. PTK7 (protein tyrosine kinase-7), RGMB (repulsive guidance molecule BMP co-receptor B), TAGLN2 (transgelin-2), TIMP3 (tissue inhibitor of metalloproteinases 3), and VIM (vimentin) were identified as promising therapeutic targets. Several proteins were found to mediate the associations between some modifiable factors and CAD, with PCSK9, C1S, AGER (advanced glycosylation end product-specific receptor), and MST1 (mammalian Ste20-like kinase 1) exhibiting highest frequency among the mediating networks.

CONCLUSIONS: This study suggests pathways explaining the associations of obesity and lifestyle factors with CAD from alterations in blood protein levels. These insights may be used to prioritize therapeutic intervention for further study.

PMID:38049831 | DOI:10.1186/s12916-023-03197-8

Ital J Pediatr. 2023 Dec 4;49(1):162. doi: 10.1186/s13052-023-01564-y.

ABSTRACT

BACKGROUND: To study whether the four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of the Kazak children in Xinjiang, China.

METHODS: Four single nucleotide polymorphisms about the 4 genes were genotyped in asthma group and control group of Han children and Kazak children respectively. The frequencies of different genotypes and alleles were compared between the asthma group and the control group in the two nationalities. Different risk genotypes for asthma were evaluated in the two nationalities.

RESULTS: The differences about frequencies of genotypes in ADRB2 rs1042713 and IL4 rs2243250 and IL13 rs20541 between asthma group and control group were statistically significant in Han children, as were the frequencies of alleles in the 3 single nucleotide polymorphisms, but there were no statistical differences in FCER1B rs569108(P > 0.05). For the Kazak children, no differences were existed among all the genotypes and alleles in asthma group and control group. For the Han children, more children were asthma high risk genotype in the asthma group than those in the control group and no difference was found in the Kazak children.

CONCLUSIONS: The four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of Han children but not for the Kazak children in Xinjiang, which illustrating that the difference of asthma prevalence between different races is closely related to the genetic background.

PMID:38049812 | DOI:10.1186/s13052-023-01564-y

BMC Med Genomics. 2023 Dec 4;16(1):314. doi: 10.1186/s12920-023-01751-0.

ABSTRACT

BACKGROUND: N⁶-methyladenosine (m⁶A) mRNA modification plays a critical role in various human biological processes. However, there has been no study reported to elucidate its role in hepatic ischemia-reperfusion injury (IRI). This study was aimed to explore the expression pattern together with the potential functions of m⁶A regulators in hepatic IRI.

METHODS: The gene expression data (GSE23649) of m⁶A regulators in human liver tissue samples before cold perfusion and within 2 h after portal vein perfusion from Gene Expression Omnibus database was analyzed. The candidate m⁶A regulators were screened using random forest (RF) model to predict the risk of hepatic IRI. The evaluation of infiltrating abundance of 23 immune cells was performed using single sample gene set enrichment analysis. Besides, quantitative real time polymerase chain reaction (qRT-PCR) assay was carried out to validate the expression of key m⁶A regulators in mouse hepatic IRI model.

RESULTS: The expressions of WTAP, CBLL1, RBM15, and YTHDC1 were found to be increased in liver tissues 2 h after portal vein perfusion; in contrast, the expressions of LRPPRC, FTO, METTL3, and ALKBH5 were decreased. Based on RF model, we identified eight m⁶A methylation regulators for the prediction of the risk of hepatic IRI. Besides, a nomogram was built to predict the probability of hepatic IRI. In addition, the levels of WTAP, ALKBH5, CBLL1, FTO, RBM15B, LRPPRC and YTHDC1 were correlated with the immune infiltration of activated CD4 T cell, activated dendritic cell (DC), immature DC, mast cell, neutrophil, plasmacytoid DC, T helper (Th) cell (type 1, 2, and 17), gamma delta T cell, T follicular helper (Tfh) cell, myeloid-derived suppressor cell (MDSC), macrophage, natural killer cell, and regulatory Th cell. Among mouse hepatic IRI model, the mRNA level of CBLL1 and YTHDC1 was increased with statistical significance; however, the mRNA level of FTO and METTL3 was decreased among post-reperfusion liver samples compared with those in pre-reperfusion samples with statistical significance.

CONCLUSIONS: The m⁶A regulators exerted a pivotal impact on hepatic IRI. The m⁶A patterns that found in this study might provide novel targets and strategies for the alleviation/treatment of hepatic IRI in the future.

PMID:38049811 | DOI:10.1186/s12920-023-01751-0

BMC Oral Health. 2023 Dec 4;23(1):964. doi: 10.1186/s12903-023-03631-6.

ABSTRACT

BACKGROUND: The surgical removal of impacted lower third molars produces a significant degree of trauma to the soft tissue and bony structures of the oral cavity, which can initiate considerable inflammatory reaction. Consequently, patient experiences pain, swelling, hemorrhage, nerve paraesthesia, limited mouth opening etc. The kinesiologic tape (KT) can help with blood and lymphatic circulation and has shown acceptable outcomes in reducing pain and in managing post-operative muscle spasm.

METHODOLOGY: The study was aimed to compare the effects of kinesiologic tape on post operative pain, swelling and trismus following surgical removal of mandibular third molar when compared to control group. 15 patients with bilaterally impacted mandibular third molar were included in the split mouth study. One side was randomly assigned as Group A where patient’s face was subjected to Kinesio tape application post extraction. The other was Group B where Kinesio tape was not applied. After extraction each patient was evaluated in terms of post op pain, swelling and trismus in post-op day 1,2 and 7^th.

RESULTS: The pain was found to be significantly less (p = 0.042) in group A when compared to group B on the first day. The mean pain was 5.07 in KT group and 6.20 in No KT group on day 2^nd. Post OP Swelling was statistically significantly less (p < 0.01) in Group A on 2^nd & 3^rd day. The postoperative mouth opening was more from the 2^nd day in group A with mean of 26.07 mm and 20.33 mm in group B (p < 0.01).

CONCLUSION: The kinesiologic taping originates from sports medicine, but can also used therapeutically for reducing post operative sequelae as demonstrated in our study. Kinesiologic tape (KT) enables patients to have a comfortable time post-operatively and helps to regain better quality of life.

TRIAL REGISTRATION: Registered in Clinical Trial Registry-India. Registration number-CTRI/2021/05/033359, registration date – 04/05/2021.

PMID:38049807 | DOI:10.1186/s12903-023-03631-6