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Over the last five decades, widespread industrialisation and urbanisation have resulted in the influx of low-skilled workers, particularly from Southeast and West Asia to Malaysia. The current practice for migrant workers entry for employment requires mandatory medical screening for infectious diseases. However, screening for parasitic infections in Malaysia is woefully inadequate. Many migrants come from low-income countries where parasitic infections are common, which may have public health implications for their overall well-being as parasitic infections, although not critical, may impact their overall productivity. The high prevalence of intestinal parasitic infections (IPIs) recorded among migrant workers in Malaysia necessitates improvement in the national health policy to include mandatory mass administration of a single dose of anthelmintic drugs to all low-skilled migrant labourers, particularly upon entry into the country, admission, and encourage continuous surveillance. A constant stream of migrant labourers is anticipated, potentially resulting in an ongoing occurrence of parasitic infections within the population. The implementation of economic measures like health awareness initiatives, routine deworming campaigns, and improved sanitation facilities holds the potential to reduce the spread of these infections notably. More often than not, taking preventive actions proves to be more financially efficient over time compared to addressing severe infections at a later stage.
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Enteropatias Parasitárias , Migrantes , Humanos , Malásia/epidemiologia , Migrantes/estatística & dados numéricos , Enteropatias Parasitárias/prevenção & controle , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/epidemiologia , Administração Massiva de Medicamentos , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Política de Saúde , PrevalênciaRESUMO
AIMS: Traditional approaches to designing clinical trials for heart failure (HF) have historically relied on expertise and past practices. However, the evolving landscape of healthcare, marked by the advent of novel data science applications and increased data availability, offers a compelling opportunity to transition towards a data-driven paradigm in trial design. This research aims to evaluate the scope and determinants of disparities between clinical trials and registries by leveraging natural language processing for the analysis of trial eligibility criteria. The findings contribute to the establishment of a robust design framework for guiding future HF trials. METHODS AND RESULTS: Interventional phase III trials registered for HF on ClinicalTrials.gov as of the end of 2021 were identified. Natural language processing was used to extract and structure the eligibility criteria for quantitative analysis. The most common criteria for HF with reduced ejection fraction (HFrEF) were applied to estimate patient eligibility as a proportion of registry patients in the ASIAN-HF (N = 4868) and BIOSTAT-CHF registries (N = 2545). Of the 375 phase III trials for HF, 163 HFrEF trials were identified. In these trials, the most frequently encountered inclusion criteria were New York Heart Association (NYHA) functional class (69%), worsening HF (23%), and natriuretic peptides (18%), whereas the most frequent comorbidity-based exclusion criteria were acute coronary syndrome (64%), renal disease (55%), and valvular heart disease (47%). On average, 20% of registry patients were eligible for HFrEF trials. Eligibility distributions did not differ (P = 0.18) between Asian [median eligibility 0.20, interquartile range (IQR) 0.08-0.43] and European registry populations (median 0.17, IQR 0.06-0.39). With time, HFrEF trials became more restrictive, where patient eligibility declined from 0.40 in 1985-2005 to 0.19 in 2016-2022 (P = 0.03). When frequency among trials is taken into consideration, the eligibility criteria that were most restrictive were prior myocardial infarction, NYHA class, age, and prior HF hospitalization. CONCLUSIONS: Based on 14 trial criteria, only one-fifth of registry patients were eligible for phase III HFrEF trials. Overall eligibility rates did not differ between the Asian and European patient cohorts.
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Intestinal parasitic infections (IPIs) can lead to significant morbidity and mortality in cancer patients. While they are unlikely to cause severe disease and are self-limiting in healthy individuals, cancer patients are especially susceptible to opportunistic parasitic infections. The gut microbiota plays a crucial role in various aspects of health, including immune regulation and metabolic processes. Parasites occupy the same environment as bacteria in the gut. Recent research suggests intestinal parasites can disrupt the normal balance of the gut microbiota. However, there is limited understanding of this co-infection dynamic among cancer patients in Malaysia. A study was conducted to determine the prevalence and relationship between intestinal parasites and gut microbiota composition in cancer patients. Stool samples from 134 cancer patients undergoing active treatment or newly diagnosed were collected and examined for the presence of intestinal parasites and gut microbiota composition. The study also involved 17 healthy individuals for comparison and control. Sequencing with 16S RNA at the V3-V4 region was used to determine the gut microbial composition between infected and non-infected cancer patients and healthy control subjects. The overall prevalence of IPIs among cancer patients was found to be 32.8%. Microsporidia spp. Accounted for the highest percentage at 20.1%, followed by Entamoeba spp. (3.7%), Cryptosporidium spp. (3.0%), Cyclospora spp. (2.2%), and Ascaris lumbricoides (0.8%). None of the health control subjects tested positive for intestinal parasites. The sequencing data analysis revealed that the gut microbiota diversity and composition were significantly different in cancer patients than in healthy controls (p < 0.001). A significant dissimilarity was observed in the bacterial composition between parasite-infected and non-infected patients based on Bray-Curtis (p = 0.041) and Jaccard (p = 0.021) measurements. Bacteria from the genus Enterococcus were enriched in the parasite-infected groups, while Faecalibacterium prausnitzii reduced compared to non-infected and control groups. Further analysis between different IPIs and non-infected individuals demonstrated a noteworthy variation in Entamoeba-infected (unweighted UniFrac: p = 0.008), Cryptosporidium-infected (Bray-Curtis: p = 0.034) and microsporidia-infected (unweighted: p = 0.026; weighted: p = 0.019; Jaccard: p = 0.031) samples. No significant dissimilarity was observed between Cyclospora-infected groups and non-infected groups. Specifically, patients infected with Cryptosporidium and Entamoeba showed increased obligate anaerobic bacteria. Clostridiales were enriched with Entamoeba infections, whereas those from Coriobacteriales decreased. Bacteroidales and Clostridium were found in higher abundance in the gut microbiota with Cryptosporidium infection, while Bacillales decreased. Additionally, bacteria from the genus Enterococcus were enriched in microsporidia-infected patients. In contrast, bacteria from the Clostridiales order, Faecalibacterium, Parabacteroides, Collinsella, Ruminococcus, and Sporosarcina decreased compared to the non-infected groups. These findings underscore the importance of understanding and managing the interactions between intestinal parasites and gut microbiota for improved outcomes in cancer patients.
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Microbioma Gastrointestinal , Enteropatias Parasitárias , Neoplasias , Humanos , Malásia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Enteropatias Parasitárias/epidemiologia , Adulto , Neoplasias/microbiologia , Idoso , Fezes/microbiologia , Fezes/parasitologia , Centros de Atenção Terciária , Hospitais de Ensino , Prevalência , Cryptosporidium/isolamento & purificação , Cryptosporidium/genética , Entamoeba/isolamento & purificação , Entamoeba/genética , Microsporídios/isolamento & purificação , Coinfecção/microbiologia , Coinfecção/epidemiologia , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Parasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminth Trichuris trichiura, display microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes with immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. In this study, we aimed to further characterize the functional properties of these bacteria. RESULTS: Clostridiales isolates were profiled for their ability to perform 57 enzymatic reactions and produce short-chain fatty acids (SCFAs) and hydrogen sulfide, revealing that these bacteria were capable of a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T-cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction and Trichuris egg hatching. CONCLUSION: We identified Clostridiales species that are sufficient to induce high levels of Tregs. We also identified a set of metabolic activities linked with Treg differentiation and Trichuris egg hatching mediated by these newly isolated bacteria. Altogether, this study provides functional insights into the microbiotas of individuals residing in a helminth-endemic region. Video Abstract.
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Diferenciação Celular , Clostridiales , Microbioma Gastrointestinal , Linfócitos T Reguladores , Trichuris , Animais , Linfócitos T Reguladores/imunologia , Camundongos , Malásia , Clostridiales/isolamento & purificação , Humanos , Ácidos Graxos Voláteis/metabolismo , Feminino , Tricuríase/parasitologia , Tricuríase/imunologia , Tricuríase/microbiologiaRESUMO
In indigenous populations where soil-transmitted helminths (STH) infections are endemic, STH parasites (i.e., Ascaris lumbricoides, Trichuris trichiura, hookworms) often co-exist and co-evolve with the gut microbiota of their human hosts. The association between STH infections and the gut microbiota of the colonized human hosts has been established, but few studies explored the gut microbiota of the parasites. This preliminary study aimed to characterize the microbiota of the STH parasite for further understanding the STH parasite-host relationship. The gut microbial genomic DNA from four adult A. lumbricoides worms recovered from a six-year-old indigenous Negrito boy living in an STH-endemic village in Perak, Peninsular Malaysia was extracted and sequenced for the V3-V4 region of the 16S rRNA. The microbiota profiles of these worms were characterized and compared with the gut microbiota of their human host, including the profiles from four STH-positive and three STH-negative individuals from the same tribe and village. The gut microbial structure of A. lumbricoides was found to be differed significantly from their human host. The worms contained lower gut bacterial abundance and diversity than human. This difference was evident in the beta diversity analysis which showed a clear separation between the two sample types. While both Firmicutes (52.3%) and Bacteroidetes (36.6%) are the predominant phyla followed by Proteobacteria (7.2%) in the human gut, the microbiota of Ascaris gut is highly dominated by Firmicutes, constituting 84.2% relative abundance (mainly from the genus Clostridium), followed by Proteobacteria (11.1%), Tenericutes (1.8%) and Bacteroidetes (1.5%). The parasites were also found to alter the microbial structure of the human gut following infection based on the relatively higher bacterial abundance in STH-positive versus STH-negative participants. Further studies with a greater number of Ascaris adults and human hosts are needed to confirm the gut microbiota profiles.
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Background: Elective surgeries were suspended during the national lockdown in March 2020 to curb the spread of the COVID-19 pandemic in Malaysia. We sought to evaluate the impact of the lockdown on cataract surgeries and suggest lessons for future outbreaks. Study design: We conducted an interrupted time series analysis to examine rates of cataract surgery before and during the lockdown. Methods: We used national cataract surgical data between 2015 and 2021 from the Malaysian Cataract Surgery Registry. Segmented regression with a seasonally adjusted Poisson model was used for the analysis. Stratified analyses were performed to establish whether the effect of the lockdown on cataract surgeries varied by hospital designation, type of cataract service, sex, and age groups. Results: Cataract surgeries began falling in March 2020 at the onset of the lockdown, reached a trough in April 2020, and subsequently increased but never recovered to pre-lockdown levels. Cataract surgical rates in December 2021 were still 43 % below the expected surgical volume, equivalent to 2513 lost cataract surgeries. There was no evidence of a differential effect of the lockdown between COVID-19 designated and non-COVID-19 designated hospitals. The relative decrease in cataract surgical rates appears to have been greatest in outreach services and in people 40 years and older. Conclusions: The lockdown caused an immediate reduction in cataract surgical rates to nearly half of its baseline rate. Despite its gradual recovery, further delays remain to be expected should there be no redistribution or increase in resources to support backlogs and incoming new cases.
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Obstructive sleep apnea (OSA) is a prevalent complication that affects up to 60% of children and adolescents with obesity. It is associated with poorer cardiometabolic outcomes and neurocognitive deficits. Appropriate screening and intervention for OSA are crucial in the management of children with obesity. We performed a scoping review of international and national pediatric obesity (n = 30) and pediatric OSA (n = 10) management guidelines to evaluate the recommendations on OSA screening in pediatric obesity. Sixteen (53%) of the pediatric obesity guidelines had incorporated OSA screening to varying extents, with no consistent recommendations on when and how to screen for OSA, and subsequent management of OSA in children with obesity. We provide our recommendations that are based on the strength and certainty of evidence presented. These include a clinical-based screening for OSA in all children with body mass index (BMI) ≥ 85th percentile or those with rapid BMI gain (upward crossing of 2 BMI percentiles) and the use of overnight polysomnography to confirm the diagnosis of OSA in those with high clinical suspicion. We discuss further management of OSA unique to children with obesity. An appropriate screening strategy for OSA would facilitate timely intervention that has been shown to improve cardiometabolic and neurocognitive outcomes.
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Doenças Cardiovasculares , Obesidade Infantil , Apneia Obstrutiva do Sono , Adolescente , Humanos , Criança , Obesidade Infantil/complicações , Obesidade Infantil/diagnóstico , Obesidade Infantil/terapia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Índice de Massa Corporal , Polissonografia , Doenças Cardiovasculares/complicaçõesRESUMO
PURPOSE: Vitamin A deficiency (VAD) remains a significant contributor to childhood morbidity and mortality in developing countries; therefore, the implementation of sustainable and cost-effective approaches to control VAD is of utmost pertinence. This study aims to investigate the efficacy of red palm olein (RPO)-enriched biscuit supplementation in improving vitamin A, haematological, iron, and inflammatory status among vitamin A-deficient schoolchildren. METHODS: We conducted a double-blinded, randomised controlled trial involving 651 rural primary schoolchildren (8-12 years) with VAD in Malaysia. The schoolchildren were randomised to receive either RPO-enriched biscuits (experimental group, n = 334) or palm olein-enriched biscuits (control group, n = 317) for 6-month duration. RESULTS: Significant improvements in retinol and retinol-binding protein 4 levels were observed in both groups after supplementation (P < 0.001). The improvement in retinol levels were similar across groups among subjects with confirmed VAD (P = 0.40). Among those with marginal VAD, greater improvement in retinol levels was recorded in the control group (P < 0.001) but lacked clinical significance. The levels of α- and ß-carotenes, haematological parameters (haemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin) and iron enhanced more significantly in the experimental group (P < 0.05). The significant reduction in the prevalence of microcytic anaemia (- 21.8%) and high inflammation (- 8.1%) was only observed in the experimental group. CONCLUSION: The supplementation of RPO-enriched biscuits enhanced levels of provitamin A carotenes, iron, and erythropoiesis, and exhibited anti-inflammatory effects. Therefore, the incorporation of RPO into National Nutritional Intervention Programs may be a potential measure to improve the health status of vitamin A-deficient children, among various other interventions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03256123).
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Deficiência de Vitamina A , Vitamina A , Criança , Humanos , Carotenoides , Provitaminas , Ferro , Eritropoese , Deficiência de Vitamina A/tratamento farmacológico , Deficiência de Vitamina A/epidemiologia , Suplementos Nutricionais , Estado NutricionalRESUMO
The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early cancer screening is needed for timely clinical intervention and may reduce mortality and morbidity, but the lack of knowledge about premalignant lesions for OPSCC poses a significant challenge to early detection. Biomarkers that identify individuals at high risk for OPSCC may act as surrogate markers for precancer but these are limited as only a few studies decipher the multistep progression from HPV infection to OPSCC development. Here, we summarize the current literature describing the multistep progression from oral HPV infection, persistence, and tumor development in the oropharynx. We also examine key challenges that hinder the identification of premalignant lesions in the oropharynx and discuss potential biomarkers for oropharyngeal precancer. Finally, we evaluate novel strategies to improve investigations of the biological process that drives oral HPV persistence and OPSCC, highlighting new developments in the establishment of a genetic progression model for HPV + OPSCC and in vivo models that mimic HPV + OPSCC pathogenesis.
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Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Papillomaviridae/genética , Neoplasias Orofaríngeas/genética , BiomarcadoresRESUMO
Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome can be an indicator of how it may affect human health and susceptibility to diseases. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of hematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response trigger, antigen dis-sequestration, and molecular mimicry, have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or hematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in hematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying the composition of the beneficial microorganisms in the management and treatment of hematological cancers is also discussed. Additionally discussed are the latest developments in modeling approaches and tools used for computational analyses, interpretation and better understanding of the gut microbiome data.
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Microbioma Gastrointestinal , Neoplasias Hematológicas , Microbiota , Humanos , Disbiose/microbiologia , Disbiose/terapia , InflamaçãoRESUMO
Sharing individual patient data (IPD) is a simple concept but complex to achieve due to data privacy and data security concerns, underdeveloped guidelines, and legal barriers. Sharing IPD is additionally difficult in big data-driven collaborations such as Bigdata@Heart in the Innovative Medicines Initiative, due to competing interests between diverse consortium members. One project within BigData@Heart, case study 1, needed to pool data from seven heterogeneous data sets: five randomized controlled trials from three different industry partners, and two disease registries. Sharing IPD was not considered feasible due to legal requirements and the sensitive medical nature of these data. In addition, harmonizing the data sets for a federated data analysis was difficult due to capacity constraints and the heterogeneity of the data sets. An alternative option was to share summary statistics through contingency tables. Here it is demonstrated that this method along with anonymization methods to ensure patient anonymity had minimal loss of information. Although sharing IPD should continue to be encouraged and strived for, our approach achieved a good balance between data transparency while protecting patient privacy. It also allowed a successful collaboration between industry and academia.
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Big Data , Confidencialidade , Humanos , Segurança Computacional , PrivacidadeRESUMO
Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Suscetibilidade a Doenças , Diabetes Mellitus Tipo 2/genética , Evolução Biológica , GenômicaRESUMO
The incidence of human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly and has exceeded cervical cancer to become the most common HPV-induced cancer in developed countries. Since patients with HPV + OPSCC respond very favorably to standard aggressive treatment, the emphasis has changed to reducing treatment intensity. However, recent multi-center clinical trials failed to show non-inferiority of de-escalation strategies on a population basis, highlighting the need to select low-risk patients likely to respond to de-intensified treatments. In contrast, there is a substantial proportion of patients who develop recurrent disease despite aggressive therapy. This supports that HPV + OPSCC is not a homogeneous disease, but comprises distinct subtypes with clinical and biological variations. The overall goal for this review is to identify biomarkers for HPV + OPSCC that may be relevant for patient stratification for personalized treatment. We discuss HPV + OPSCC as a heterogeneous disease from multifaceted perspectives including clinical behavior, tumor morphology, and molecular phenotype. Molecular profiling from bulk tumors as well as single-cell sequencing data are discussed as potential driving factors of heterogeneity between tumor subgroups. Finally, we evaluate key challenges that may impede in-depth investigations of HPV + OPSCC heterogeneity and outline potential future directions, including a section on racial and ethnic differences.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Papillomaviridae/genéticaRESUMO
Mucositis is a debilitating complication of hematopoietic stem cell transplantation (HSCT). It is unclear how changes in the composition of microbiota, which are modulated by geographical location and ethnicity, may influence immune regulation leading to the development of mucositis, and the study of both oral and gut microbiota in a single population of autologous HSCT in the Asian region is lacking. The present study aimed to characterize the oral and gut microbiota changes, and the impact on both oral and lower gastrointestinal (GI) mucositis, with associated temporal changes in a population of adult recipients of autologous HSCT. Autologous HSCT recipients age ≥18 years were recruited from Hospital Ampang, Malaysia, between April 2019 and December 2020. Mucositis assessments were conducted daily, and blood, saliva, and fecal samples were collected prior to conditioning, on day 0, and at 7 days and 6 months post-transplantation. Longitudinal differences in alpha diversity and beta diversity were determined using the Wilcoxon signed-rank test and permutational multivariate analysis of variance, respectively. Changes in relative abundances of bacteria across time points were assessed using the microbiome multivariate analysis by linear models function. The combined longitudinal effects of clinical, inflammatory, and microbiota variables on mucositis severity were measured using the generalized estimating equation. Among the 96 patients analyzed, oral mucositis and diarrhea (representing lower GI mucositis) occurred in 58.3% and 95.8%, respectively. Alpha and beta diversities were significantly different between sample types (P < .001) and across time points, with alpha diversity reaching statistical significance at day 0 in fecal samples (P < .001) and at day +7 in saliva samples (P < .001). Diversities normalized to baseline by 6 months post-transplantation. Significant microbiota, clinical, and immunologic factors were associated with increasing mucositis grades. Increasing relative abundances of saliva Paludibacter, Leuconostoc, and Proteus were associated with higher oral mucositis grades, whereas increasing relative abundances of fecal Rothia and Parabacteroides were associated with higher GI mucositis grades. Meanwhile, increasing relative abundances of saliva Lactococcus and Acidaminococcus and fecal Bifidobacterium were associated with protective effects against worsening oral and GI mucositis grades, respectively. This study provides real-world evidence and insights into the dysbiosis of the microbiota in patients exposed to conditioning regimen during HSCT. Independent of clinical and immunologic factors, we demonstrated significant associations between relative bacteria abundances with the increasing severity of oral and lower GI mucositis. Our findings offer a potential rationale to consider the inclusion of preventive and restorative measures targeting oral and lower GI dysbiosis as interventional strategies to ameliorate mucositis outcome in HSCT recipients.
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PURPOSE: The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its' associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT). METHODS: Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively. RESULTS: Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16-72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68-12.3, p = 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05-14.5, p = 0.023), female sex (OR = 3.3, 95% CI 1.43-7.44, p = 0.004) and body mass index (OR=1.08, 95% CI 1.02-1.15, p = 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001-1.004, p < 0.001 and OR=1.01, 95% CI 1.001-1.015, p = 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85-0.99, p = 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model. CONCLUSION: This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.
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Transplante de Células-Tronco Hematopoéticas , Mucosite , Estomatite , Adulto , Humanos , Feminino , Adolescente , Mucosite/epidemiologia , Mucosite/etiologia , Bussulfano , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Prospectivos , Estomatite/epidemiologia , Estomatite/etiologia , Citocinas , Transplante de Células-Tronco/efeitos adversos , Fatores de Risco , Fatores Imunológicos , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Parasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminth Trichuris trichiura, displayed microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes previously shown to have immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. Here, we further characterized the functional properties of these bacteria. Enzymatic and metabolomic profiling revealed a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction and Trichuris egg hatching. These results provide functional insights into the microbiotas of an understudied population.
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AIMS: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. METHODS AND RESULTS: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males). CONCLUSION: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Masculino , Feminino , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Caracteres Sexuais , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunção Ventricular Esquerda/complicações , Sistema de Registros , HospitalizaçãoRESUMO
AIMS: To evaluate the effectiveness of the Enhanced Primary Healthcare (EnPHC) interventions on process of care and intermediate clinical outcomes among type 2 diabetes patients. METHODS: This was a quasi-experimental controlled study conducted in 20 intervention and 20 control public primary care clinics in Malaysia from November 2016 to June 2019. Type 2 diabetes patients aged 30 years and above were selected via systematic random sampling. Outcomes include process of care and intermediate clinical outcomes. Difference-in-differences analyses was conducted. RESULTS: We reviewed 12,017 medical records of patients with type 2 diabetes. Seven process of care measures improved: HbA1c tests (odds ratio (OR) 3.31, 95% CI 2.13, 5.13); lipid test (OR 4.59, 95% CI 2.64, 7.97), LDL (OR 4.33, 95% CI 2.16, 8.70), and urine albumin (OR 1.99, 95% CI 1.12, 3.55) tests; BMI measured (OR 15.80, 95% CI 4.78, 52.24); cardiovascular risk assessment (OR 174.65, 95% CI 16.84, 1810.80); and exercise counselling (OR 1.18, 95% CI 1.04, 1.33). We found no statistically significant changes in intermediate clinical outcomes (i.e. HbA1c, LDL, HDL and BP control). CONCLUSIONS: EnPHC interventions was successful in enhancing the quality of care, in terms of process of care, by changing healthcare providers behaviour.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas , Malásia , Exercício Físico , Atenção Primária à SaúdeRESUMO
Objective: Mucositis is one of the most feared side effects of cancer treatment. Psychometric analysis of a patient self-assessment score, the oral mucositis daily questionnaire in Malay (OMDQ-Mal) and its construct validity by means of confirmatory factor analysis (CFA) is lacking. This research aimed to test the validity and reliability of OMDQ-Mal. Methods: A total of 114 autologous stem-cell transplantation patients aged ≥ 18 years old at a national hematology center in Malaysia from April 2019 to December 2020 completed OMDQ-Mal concurrently with physician scores. Internal consistency and reproducibility were determined by Cronbach alpha and intraclass correlation coefficient, respectively. Correlations with physician scores were determined by Spearman correlation. Discriminative validity and construct validity were determined by Mann-Whitney U and CFA, respectively. Results: OMDQ-Mal demonstrated high internal consistency (α â= â0.874). Test-retest reliability between paired days were moderate to excellent (95% CI â= â0.676-0.953). Items in OMDQ-Mal had moderate to strong correlations with physician scores (ρ â= â0.503-0.721). Discriminative validity indicated that the scores of scales were significantly different between participants with severe and mild conditions. Construct validity results of loading factors 0.708-0.952; composite reliability 0.879-0.974; average variant extracted 0.710-0.841; and heterotrait-monotrait ratio 0.528 established the convergent and divergent validity. Conclusions: In conclusion, the OMDQ-Mal, which captured important quality of life responses, demonstrated adequate validity and reliability. This was supported by a two-component model CFA. The strong correlation of OMDQ-Mal with both physician scores indicated its potential as a comprehensive patient-reported outcome measure of mucositis of the entire alimentary tract.
RESUMO
BACKGROUND: Obesity and obesity-related morbidities are associated with poor psychosocial adjustment and health-related quality of life (HRQoL). This study aims to examine HRQoL and psychosocial outcomes in children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and the effects of familial health on these outcomes. METHODS: Four hundred and six children with BMI for age ≥ 97th percentile were classified as having MHO and MUO based on the absence or presence of metabolic abnormalities. HRQoL and psychosocial outcomes were assessed using validated questionnaires such as PedsQL and DASS-21. RESULTS: There were no significant differences in HRQoL and psychosocial outcomes between children with MHO and children with MUO. Children with MUO and prior knowledge of existing metabolic conditions reported significantly lower total HRQoL (71.18 ± 17.42 vs. 75.34 ± 15.33), and higher depression (12.16 ± 11.80 vs. 8.95 ± 8.52) and stress (12.11 ± 8.21 vs. 10.04 ± 7.92) compared to children with MHO. Children with MUO who had fathers with metabolically unhealthy phenotype reported significantly lower total HRQoL (72.41 ± 15.67 vs. 76.82 ± 14.91) compared to children with MUO who had fathers with metabolically healthy phenotype. CONCLUSION: Prior knowledge of existing metabolic abnormalities was associated with poorer HRQoL and mental health in children with obesity. Paternal metabolic health status influenced HRQoL in children with MUO. IMPACT: First study that compared health-related quality of life (HRQoL) and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). No significant differences in HRQoL and psychosocial outcomes between children with metabolically healthy obesity (MHO) and children with metabolically unhealthy obesity (MUO). Children with MUO who had prior knowledge of existing metabolic conditions reported lower HRQoL, higher depression and stress compared to children with MHO. Paternal metabolic health status was found to influence HRQoL in children with MUO. Mental health support intervention with paternal involvement should be provided for children with MUO.