Nevin Manimala

Curr Rheumatol Rev. 2024 Feb 15. doi: 10.2174/0115733971290285240207080745. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB).

OBJECTIVE: This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB.

METHODS: A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression.

RESULTS: Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (ORA) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an ORA of 6.17 (95% CI 1.79- 21.24).

CONCLUSION: This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.

PMID:38362696 | DOI:10.2174/0115733971290285240207080745

Pharmacoepidemiol Drug Saf. 2024 Feb;33(2):e5750. doi: 10.1002/pds.5750.

ABSTRACT

PURPOSE: Outcome variables that are assumed to follow a negative binomial distribution are frequently used in both clinical and epidemiological studies. Epidemiological studies, particularly those performed by pharmaceutical companies often aim to describe a population rather than compare treatments. Such descriptive studies are often analysed using confidence intervals. While precision calculations and sample size calculations are not always performed in these settings, they have the important role of setting expectations of what results the study may generate. Current methods for precision calculations for the negative binomial rate are based on plugging in parameter values into the confidence interval formulae. This method has the downside of ignoring the randomness of the confidence interval limits. To enable better practice for precision calculations, methods are needed that address the randomness.

METHODS: Using the well-known delta-method we develop a method for calculating the precision probability, that is, the probability of achieving a certain width. We assess the performance of the method in smaller samples through simulations.

RESULTS: The method for the precision probability performs well in small to medium sample sizes, and the usefulness of the method is demonstrated through an example.

CONCLUSIONS: We have developed a simple method for calculating the precision probability for negative binomial rates. This method can be used when planning epidemiological studies in for example, asthma, while correctly taking the randomness of confidence intervals into account.

PMID:38362649 | DOI:10.1002/pds.5750

Lab Chip. 2024 Feb 16. doi: 10.1039/d3lc01020a. Online ahead of print.

ABSTRACT

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based “3P model” framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning.

PMID:38362645 | DOI:10.1039/d3lc01020a

Euro Surveill. 2024 Feb;29(7). doi: 10.2807/1560-7917.ES.2024.29.7.2300259.

ABSTRACT

Many vaccine effectiveness (VE) analyses of severe disease outcomes such as hospitalisation and death include ‘false’ cases that are not actually caused by the infection or disease under study. While the inclusion of such false cases inflate outcome rates in both vaccinated and unvaccinated populations, it is less obvious how they affect estimates of VE. Illustrating the main points through simple examples, this article shows how VE is underestimated when false cases are included as outcomes. Depending how the outcome indicator is defined, estimates of VE against severe disease outcomes, whose definition allows for the inclusion of false cases, will be biased downwards and may in certain circumstances approximate the same level as the VE against infection. The bias is particularly pronounced for vaccines that offer high levels of protection against severe disease outcomes but poor protection against infection. Analysing outcomes that are measured with low sensitivity generally does not cause bias in VE studies; defining outcome indicators that minimise the number of false cases rather than the number of missed cases is preferable in VE studies.

PMID:38362627 | DOI:10.2807/1560-7917.ES.2024.29.7.2300259

Birth Defects Res. 2024 Feb;116(2):e2318. doi: 10.1002/bdr2.2318.

ABSTRACT

BACKGROUND: Arginase 1 (Arg1) encodes a key enzyme that catalyzes the metabolism of arginine to ornithine and urea. In our recent study, we found that knockdown of Arg1 in the lungs of fetal mice induces apoptosis of epithelial cells and dramatically delays initiation of labor. As the most abundant internal mRNA modification, N⁶ -methyladenosine (m⁶ A) has been found to play important roles in lung development and cellular differentiation. However, if the knockdown of Arg1 affects the RNA m6A modification in fetal lungs remains unknown.

METHODS: In the current study, the RNA m6A levels and the expression of RNA m6A related enzymes were validated in 13.0 dpc fetal lungs that Arg1 was knocked down by adeno-associated virus carrying Arg1-shRNA, using western blot, immunofluorescence, and RT-qPCR.

RESULTS: No statistical differences were found in the expression of methyltransferase, demethylases, and binding proteins in the fetal lungs between AAV-shArg1-injected mice and AAV-2/9-injected mice. Besides, there is no significant change of overall RNA m6A level in fetal lungs from AAV-shArg1-injected mice, compared with that from AAV-2/9-injected mice.

CONCLUSIONS: These results indicate that arginase 1 does not affect RNA m6A methylation in mouse fetal lung, and the mechanisms other than RNA m6A modification underlying the effects of Arg1 knockdown on the fetal lung development and their interaction with labor initiation need to be further explored.

PMID:38362594 | DOI:10.1002/bdr2.2318

Malawi Med J. 2023 Dec;35(4):220-223. doi: 10.4314/mmj.v35i4.4.

ABSTRACT

BACKGROUND: Tracheobronchial variations (TBVs) are more common than previously believed due to the increasing use of multi-detector computed tomography (MDCT). This study aimed to assess TBVs in cases of pneumoconiosis, one of the oldest occupational diseases that still poses a threat to public health.

METHODS: This was a descriptive study that involved reviewing chest MDCT images of 34 cases of pneumoconiosis and 34 control cases retrospectively from January 2020 to April 2022. Variations in the trachea, right main bronchus, left main bronchus, lobar and segmental branches of the cases in the patient and control groups were evaluated according to Boyden’s nomenclature.

RESULTS: The frequency of TBV was 32.4% in pneumoconiosis cases. Although the frequency of TBV was higher in the patient group than in the control group, the difference was not statistically significant (p=0.086). Furthermore, there was no significant difference in terms of TBV classification between the patient and control groups (p=0.407). Additionally, the presence of TBV did not affect the distribution of International Labour Organization categories in pneumoconiosis cases (p=0.360).

CONCLUSIONS: Although our study provides initial insights into the occurrence of TBVs in pneumoconiosis cases, further research is needed to clarify the relationship between these variations and the disease.

PMID:38362566 | PMC:PMC10865055 | DOI:10.4314/mmj.v35i4.4

BMJ Open Sport Exerc Med. 2024 Feb 14;10(1):e001795. doi: 10.1136/bmjsem-2023-001795. eCollection 2024.

ABSTRACT

There is increasing interest in the potential long-term outcomes of participation in contact and collision sports, driven by evidence of higher rates of neurodegenerative diseases among former athletes. Recent research has capitalised on large-scale administrative health data to examine health outcomes in contact sport athletes. However, there is limited research on outcomes associated with participation in rugby union, a contact sport with a relatively high incidence of head trauma and musculoskeletal injuries. Additionally, there is scope to investigate a greater range of health outcomes using large, population-based administrative data. The Kumanu Tāngata project is a retrospective cohort study that will use linked information from the New Zealand Rugby Register and health records within a comprehensive deidentified whole-population administrative research database known as the Integrated Data Infrastructure. First-class male rugby union players (N=13 227) will be compared with a general population comparison group (N=2 438 484; weighting will be applied due to demographic differences) on a range of mortality and morbidity outcomes (neurodegenerative diseases, musculoskeletal conditions, chronic physical conditions, mental health outcomes). A range of player-specific variables will also be investigated as risk factors. Analyses will consist primarily of Cox proportional hazards models. Ethics approval for the study has been granted by the Auckland Health Research Ethics Committee (Ref. AH23203). Primary research dissemination will be via peer-reviewed journal articles.

PMID:38362564 | PMC:PMC10868174 | DOI:10.1136/bmjsem-2023-001795

Afr J Disabil. 2017 Aug 29;6:294. doi: 10.4102/ajod.v6i0.294. eCollection 2017.

ABSTRACT

BACKGROUND: As the South African government re-engineers primary healthcare (PHC), the need for additional information on stakeholders involved in the process has emerged. Of these are community health workers (CHWs), who have been identified as central to PHC success.

OBJECTIVES: To profile the current CHWs within KwaDabeka and Clermont in KwaZulu-Natal, to describe their roles and to explore the barriers and enablers influencing their service delivery.

METHOD: A convergent mixed methods design was employed with a sample of CHWs with the use of a survey (n = 53) and two focus groups (n = 10) and semi-structured interviews with four ward councillors (n = 4). Data were analysed statistically and thematically.

RESULTS: The profile of CHWs reflected only women with a mixed age range and a majority of 59% who had not completed formal schooling. General work experience as a CHW varied. There were diverse opinions expressed towards the CHW role which related to their job title and identity, supervision, remuneration, growth pathways and psychological and emotional issues. Whilst the National Community Health Worker Profile Framework was established for the CHW programme, there are several factors lacking in the current CHW programme such as a formal growth pathway or formal training to align the CHWs with the National Qualifications Framework.

CONCLUSION: The study findings are essential for the monitoring and evaluation as well as development and refinement of policies that will assist in ensuring adequate rollout of PHC with CHWs.

PMID:38362540 | PMC:PMC10867674 | DOI:10.4102/ajod.v6i0.294

Harv Data Sci Rev. 2020 Fall;2(4). doi: 10.1162/99608f92.33703976. Epub 2020 Dec 16.

ABSTRACT

Reproducibility and replicability play a pivotal role in science. The article reflects on reproducibility and replicability as they figure in large scale genome-wide association studies. Overall, we emphasize the importance of enhancing data reproducibility, analysis reproducibility, and result replicability. We make recommendations pertaining to the development of study designs that address 1) batch effects and selection bias, 2) the incorporation of discrete discovery and replication phases, and 3) the procurement of a large sample size. We emphasize the importance of systematic and transparent data generation, processing, and quality control pipelines, as well as a rigorous field-specific standardized analysis protocol, We offer guidance with respect to collaborative frameworks, open access analysis tools, and software, and the use of supporting mandates, infrastructure, and repositories for data and resource sharing. Finally, we identify the role of incentives and culture in fueling the production of reproducible and replicable research through partnerships of researchers, funding agencies, and journals.

PMID:38362534 | PMC:PMC10869125 | DOI:10.1162/99608f92.33703976

Anim Nutr. 2023 Dec 4;16:313-325. doi: 10.1016/j.aninu.2023.11.008. eCollection 2024 Mar.

ABSTRACT

The present study was to explore the Ile requirement of piglets fed 18% crude protein (CP) diets. Two hundred and fifty 28-day-old Duroc × Landrace × Yorkshire piglets (8.37 ± 1.92 kg) were randomly divided into 5 dietary treatments (10 piglets per replicate, 5 barrows and 5 gilts per replicate) with 45%, 50%, 55%, 60%, 65% standardized ileal digestible (SID) Ile-to-Lys ratios, and the SID Lys was formulated to 1.19%. The experimental design consisted of two phases (d 1 to 14 and d 15 to 28). Results showed that average daily gain (ADG) had a tendency to quadratically increase as the SID Ile-to-Lys ratio increased (P = 0.09), and the optimum SID Ile-to-Lys ratios required to maximize ADG were 48.33% and 54.63% for broken-line linear model and quadratic polynomial model, respectively. Different SID Ile-to-Lys ratios had no significant effects on average daily feed intake and gain-to-feed ratio. Dry matter (P < 0.01), CP (P = 0.01), ether extract (P = 0.04), gross energy (P < 0.01) and organic matter (P < 0.01) digestibility increased quadratically. Serum total cholesterol levels decreased linearly (P = 0.01) and quadratically (P < 0.01); aspartate aminotransferase (P < 0.01), interleukin-1β (P = 0.01), and tumor necrosis factor-α (P < 0.01) levels decreased quadratically; immunoglobulin G (P = 0.03) and immunoglobulin M (P = 0.01) concentrations increased quadratically. Serum Ser levels decreased linearly (P < 0.01) and quadratically (P = 0.01); Glu (P = 0.02), Arg (P = 0.05), and Thr (P = 0.03) levels decreased quadratically; Gly (P < 0.01) and Leu (P = 0.01) levels decreased linearly; Ile (P < 0.01) concentration increased linearly. Duodenal villus height (P < 0.01) and villus height to crypt depth ratio (P < 0.01) increased quadratically. The deficiency or excess of Ile decreased short chain fatty acid-producing bacteria abundance and increased pathogenic bacteria abundance. Overall, taking ADG as the effect index, the optimum SID Ile-to-Lys ratios of piglets offered 18% CP diets were 48.33% and 54.63% based on two different statistical models, respectively, and the deficiency or excess of lle negatively affected piglet growth rates and health status.

PMID:38362516 | PMC:PMC10867559 | DOI:10.1016/j.aninu.2023.11.008