Prevalence, Clinical Characteristics and Determinants of Unsuccessful Treatment Outcomes Among Pulmonary Tuberculosis Patients: A 5-Year Registry-Based Retrospective Cohort Study

Hind M AlOsaimi,1 Mohammed K Alshammari,2 Ghadah K Almijlad,3 Nawaf M Alotaibi,3 Dhafer A Alqahtani,4 Mohammed M Alshamrani,5 Tariq A Shutur,6 Mansior F Alhazmi,6 Mohammed A Hurubi,6 Kutayd S ALShammari,6 Khalid M Alzahrani,7 Hadeel M Aldaghriri,7 Anood A Alshammari,8 Oudah S Alatawi,8 Reema A Alharbi9 1Department of Pharmacy Services Administration, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; 2Department of Clinical Pharmacy, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia; 3Department of Clinical Pharmacy, Northern Border University, Rafha, Kingdom of Saudi Arabia; 4Department of Pharmacy, Security Forces Hospital, Riyadh, Kingdom of Saudi Arabia; 5Department of Respiratory Care, Northern Armed Area Forced Hospital, Hafar al Batin, Kingdom of Saudi Arabia; 6Department of Supply and Logistics, Northern Armed Area Forced Hospital, Hafar Al Batin, Kingdom of Saudi Arabia; 7Department of Radiology, Northern Armed Area Forced Hospital, Hafar Al Batin, Kingdom of Saudi Arabia; 8Pharmaceutical Services Department, Northern Area Armed Forces Hospital, King Khalid Military, Hafr Al Batin, Kingdom of Saudi Arabia; 9Department of Medicine, University of Tabuk, Tabuk, Saudi ArabiaCorrespondence: Mohammed K Alshammari, Department of Clinical Pharmacy, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia, Email [email protected]: Despite the existence of effective medications, pulmonary tuberculosis (PTB) remains a significant global public health concern, The evaluation and feedback of national TB control programs are crucial, requiring diligent monitoring of TB treatment outcomes and analysis of the factors influencing these outcomes. This study aims to provide valuable insights into the challenges faced by TB patients, which can inform better strategies for treatment and management in the future.Patients and Methods: We conducted a study in King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia (KSA), from January 1, 2018 to December 31, 2023. The study was a registry-based retrospective cohort study. Patients’ data were sourced from the National Tuberculosis Registry database of Saudi Arabia. Treatment outcomes were determined as either success or failure, considering clinical evaluation, changes in chest X-rays, and the results of subsequent sputum examinations during follow-up. To evaluate the data, SPSS version 28.0 was used.Results: A total of 427 PTB patients participated in the study. The results show successful treatment outcomes among 88.5% of patients. Among the patients, males exhibited a higher likelihood of treatment failure as compared to females (aOR 1.3; 95%Cl 1.2– 1.5, p < 0.001). Patients with positive sputum smear (aOR 1.3; 95%Cl 1.1– 1.3 p < 0.00) and the presence of cough were associated with an increased risk of treatment failure (aOR1.5; 95%Cl 1.1– 1.4, p < 0.001).Conclusion: This study shows that the percentage of unsuccessful treatment outcomes is high, ie, 11.5%, due to patients’ deaths and loss to follow-up. Enhanced supervision and treatment monitoring for tuberculosis patients at high risk of treatment failure can lead to improved treatment success rates in Saudi Arabia.Keywords: tuberculosis, treatment outcomes, retrospective study, Saudi Arabi

Self-reported use of complementary and alternative medicine (CAM) products in topical treatment of diabetic foot disorders by diabetic patients in Jeddah, Western Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>There is little published on current Saudi diabetic patients' practices when they are exposed to foot disorders such as open wound, ulcer, and skin cracks. These factors are usually influenced by local culture and communities beliefs. The aim of the current study was to identify the pattern of patients' use of CAM products in dealing with diabetic foot disorders topically in a group of diabetic patients.</p> <p>Findings</p> <p>A Cross-sectional descriptive study of a representative cohort of diabetic patients living in Jeddah, Saudi Arabia was designed. A pre-designed questionnaire to identify local diabetics' practices in dealing topically with foot disorders including open wound, chronic ulcer, and skin cracks was designed. Questionnaire was administered by a group of trained nutrition female students to diabetics face to face living in their neighborhood. A total of 1634 Saudi diabetics were interviewed. Foot disorders occurred in approximately two thirds of the respondents 1006 (61.6%). Out of the 1006 patients who had foot disorders, 653 reported trying some sort of treatment as 307 patients (47.1%) used conventional topical medical treatment alone, 142 (21.7%) used CAM products alone, and 204 (31.2%) used both treatments. The most commonly used CAM product by the patients was Honey (56.6%) followed by Commiphora Molmol (Myrrh) in (37.4%) and Nigellia Sativa (Black seed) in (35.1%). The least to be used was Lawsonia inermis (Henna) in (12.1%). Ten common natural preparations used topically to treat diabetic foot disorders were also identified.</p> <p>Conclusions</p> <p>The use of CAM products in topical treatment of diabetic foot disorders is fairly common among Saudi diabetic patients. Honey headed the list as a solo topical preparation or in combination with other herbs namely black seeds and myrrh. The efficacy of the most common products needs further research.</p

The growth inhibitory potential and antimetastatic effect of camel urine on breast cancer cells in vitro and in vivo

Although it may sound unpleasant, camel urine has been consumed extensively for years in the Middle East as it is believed to be able to treat a wide range of diseases such as fever, cold, or even cancer. People usually take it by mixing small drops with camel milk or take it directly. The project aims to study the effects of camel urine in inhibiting the growth potential and metastatic ability of 4T1 cancer cell line in vitro and in vivo. Based on the MTT result, the cytotoxicity of camel urine against 4T1 cell was established, and it was dose-dependent. Additionally, the antimetastatic potential of camel urine was tested by running several assays such as scratch assay, migration and invasion assay, and mouse aortic ring assay with promising results in the ability of camel urine to inhibit metastatic process of the 4T1 cells. In order to fully establish camel urine’s potential, an in vivo study was carried out by treating mice inoculated with 4T1 cells with 2 different doses of camel urine. By the end of the treatment period, the tumor in both treated groups had reduced in size as compared to the control group. Additional assays such as the TUNEL assay, immunophenotyping, cytokine level detection assay, clonogenic assay, and proteome profiler demonstrated the capability of camel urine to reduce and inhibit the metastatic potential of 4T1 cells in vivo. To sum up, further study of anticancer properties of camel urine is justified, as evidenced through the in vitro and in vivo studies carried out. Better results were obtained at higher concentration of camel urine used in vivo. Apart from that, this project has laid out the mechanisms employed by the substance to inhibit the growth and the metastatic process of the 4T1 cell

Global, regional, and national burden of low back pain, 1990–2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background: Low back pain is highly prevalent and the main cause of years lived with disability (YLDs). We present the most up-to-date global, regional, and national data on prevalence and YLDs for low back pain from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Methods: Population-based studies from 1980 to 2019 identified in a systematic review, international surveys, US medical claims data, and dataset contributions by collaborators were used to estimate the prevalence and YLDs for low back pain from 1990 to 2020, for 204 countries and territories. Low back pain was defined as pain between the 12th ribs and the gluteal folds that lasted a day or more; input data using alternative definitions were adjusted in a network meta-regression analysis. Nested Bayesian meta-regression models were used to estimate prevalence and YLDs by age, sex, year, and location. Prevalence was projected to 2050 by running a regression on prevalence rates using Socio-demographic Index as a predictor, then multiplying them by projected population estimates. Findings: In 2020, low back pain affected 619 million (95% uncertainty interval 554–694) people globally, with a projection of 843 million (759–933) prevalent cases by 2050. In 2020, the global age-standardised rate of YLDs was 832 per 100 000 (578–1070). Between 1990 and 2020, age-standardised rates of prevalence and YLDs decreased by 10·4% (10·9–10·0) and 10·5% (11·1–10·0), respectively. A total of 38·8% (28·7–47·0) of YLDs were attributed to occupational factors, smoking, and high BMI. Interpretation: Low back pain remains the leading cause of YLDs globally, and in 2020, there were more than half a billion prevalent cases of low back pain worldwide. While age-standardised rates have decreased modestly over the past three decades, it is projected that globally in 2050, more than 800 million people will have low back pain. Challenges persist in obtaining primary country-level data on low back pain, and there is an urgent need for more high-quality, primary, country-level data on both prevalence and severity distributions to improve accuracy and monitor change. Funding: Bill and Melinda Gates Foundation

SPARC 2018 Internationalisation and collaboration : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2018 SPARC conference. This year we not only celebrate the work of our PGRs but also the launch of our Doctoral School, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 100 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

Expanding the genetic heterogeneity of intellectual disability

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms

Dapsone‐ and nitroso dapsone‐specific activation of T cells from hypersensitive patients expressing the risk allele HLA‐B*13:01

BACKGROUND:Research into drug hypersensitivity associated with expression of specific HLA alleles has focussed on the interaction between parent drug and the HLA with no attention given to reactive metabolites. For this reason, we have studied HLA-B*13:01-linked dapsone hypersensitivity to (1) explore whether the parent drug and/or nitroso metabolite activates T-cells and (2) determine whether HLA-B*13:01 is involved in the response. METHODS:PBMC from 6 patients were cultured with dapsone and nitroso dapsone and proliferative responses and IFN-γ release were measured. Dapsone- and nitroso dapsone-specific T-cell clones were generated and phenotype, function, HLA allele restriction and cross-reactivity assessed. Dapsone intermediates were characterized by mass spectrometry. RESULTS:PBMC from 6 patients and cloned T-cells proliferated and secreted Th1/2/22 cytokines when stimulated with dapsone (clones: n=395; 80% CD4+ CXCR3hi CCR4hi , 20% CD8+CXCR3hi CCR4hi CCR6hi CCR9hi CCR10hi ) and nitroso dapsone (clones: n=399; 78% CD4+, 22% CD8+ with same chemokine receptor profile). CD4+ and CD8+ clones were HLA-class II and class I restricted, respectively, and displayed three patterns of reactivity: compound-specific, weakly crossreactive and strongly cross reactive. Nitroso dapsone formed dimers in culture and was reduced to dapsone, providing a rationale for the crossreactivity. T-cell responses to nitroso dapsone were dependent on the formation of a cysteine-modified protein adduct, while dapsone interacted in a labile manner with antigen presenting cells. CD8+ clones displayed an HLA-B*13:01-restricted pattern of activation. CONCLUSION:These studies describe the phenotype and function of dapsone- and nitroso dapsone-responsive CD4+ and CD8+ T-cells from hypersensitive patients. Discovery of HLA-B*13:01-restricted CD8+ T-cell responses indicates that drugs and their reactive metabolites participate in HLA allele-linked forms of hypersensitivity. This article is protected by copyright. All rights reserved