Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

Periodic synchronisation of dengue epidemics in Thailand over the last 5 decades driven by temperature and immunity.

The spatial distribution of dengue and its vectors (spp. Aedes) may be the widest it has ever been, and projections suggest that climate change may allow the expansion to continue. However, less work has been done to understand how climate variability and change affects dengue in regions where the pathogen is already endemic. In these areas, the waxing and waning of immunity has a large impact on temporal dynamics of cases of dengue haemorrhagic fever. Here, we use 51 years of data across 72 provinces and characterise spatiotemporal patterns of dengue in Thailand, where dengue has caused almost 1.5 million cases over the last 30 years, and examine the roles played by temperature and dynamics of immunity in giving rise to those patterns. We find that timescales of multiannual oscillations in dengue vary in space and time and uncover an interesting spatial phenomenon: Thailand has experienced multiple, periodic synchronisation events. We show that although patterns in synchrony of dengue are similar to those observed in temperature, the relationship between the two is most consistent during synchronous periods, while during asynchronous periods, temperature plays a less prominent role. With simulations from temperature-driven models, we explore how dynamics of immunity interact with temperature to produce the observed patterns in synchrony. The simulations produced patterns in synchrony that were similar to observations, supporting an important role of immunity. We demonstrate that multiannual oscillations produced by immunity can lead to asynchronous dynamics and that synchrony in temperature can then synchronise these dengue dynamics. At higher mean temperatures, immune dynamics can be more predominant, and dengue dynamics more insensitive to multiannual fluctuations in temperature, suggesting that with rising mean temperatures, dengue dynamics may become increasingly asynchronous. These findings can help underpin predictions of disease patterns as global temperatures rise.

Spatial distribution of poultry farms using point pattern modelling: A method to address livestock environmental impacts and disease transmission risks.

The distribution of farm locations and sizes is paramount to characterize patterns of disease spread. With some regions undergoing rapid intensification of livestock production, resulting in increased clustering of farms in peri-urban areas, measuring changes in the spatial distribution of farms is crucial to design effective interventions. However, those data are not available in many countries, their generation being resource-intensive. Here, we develop a farm distribution model (FDM), which allows the prediction of locations and sizes of poultry farms in countries with scarce data. The model combines (i) a Log-Gaussian Cox process model to simulate the farm distribution as a spatial Poisson point process, and (ii) a random forest model to simulate farm sizes (i.e. the number of animals per farm). Spatial predictors were used to calibrate the FDM on intensive broiler and layer farm distributions in Bangladesh, Gujarat (Indian state) and Thailand. The FDM yielded realistic farm distributions in terms of spatial clustering, farm locations and sizes, while providing insights on the factors influencing these distributions. Finally, we illustrate the relevance of modelling realistic farm distributions in the context of epidemic spread by simulating pathogen transmission on an array of spatial distributions of farms. We found that farm distributions generated from the FDM yielded spreading patterns consistent with simulations using observed data, while random point patterns underestimated the probability of large outbreaks. Indeed, spatial clustering increases vulnerability to epidemics, highlighting the need to account for it in epidemiological modelling studies. As the FDM maintains a realistic distribution of farm location and sizes, its use to inform mathematical models of disease transmission is particularly relevant for regions where these data are not available.

Assessing the role of multiple mechanisms increasing the age of dengue cases in Thailand.

The mean age of dengue hemorrhagic fever (DHF) cases increased considerably in Thailand from 8.1 to 24.3 y between 1981 and 2017 (mean annual increase of 0.45 y). Alternative proposed explanations for this trend, such as changes in surveillance practices, reduced mosquito­human contact, and shifts in population demographics, have different implications for global dengue epidemiology. To evaluate the contribution of each of these hypothesized mechanisms to the observed data, we developed 20 nested epidemiological models of dengue virus infection, allowing for variation over time in population demographics, infection hazards, and reporting rates. We also quantified the effect of removing or retaining each source of variation in simulations of the age trajectory. Shifts in the age structure of susceptibility explained 58% of the observed change in age. Adding heterogeneous reporting by age and reductions in per-serotype infection hazard to models with shifts in susceptibility explained an additional 42%. Reductions in infection hazards were mostly driven by changes in the number of infectious individuals at any time (another consequence of shifting age demographics) rather than changes in the transmissibility of individual infections. We conclude that the demographic transition drives the overwhelming majority of the observed change as it changes both the age structure of susceptibility and the number of infectious individuals. With the projected Thai population age structure, our results suggest a continuing increase in age of DHF cases, shifting the burden toward individuals with more comorbidity. These insights into dengue epidemiology may be relevant to many regions of the globe currently undergoing comparable changes in population demographics.

Naturally Acquired Transmission-Blocking Immunity Against Different Strains of Plasmodium vivax in a Malaria-Endemic Area in Thailand.

BACKGROUND: Human immunity triggered by natural malaria infections impedes parasite transmission from humans to mosquitoes, leading to interest in transmission-blocking vaccines. However, immunity characteristics, especially strain specificity, remain largely unexplored. We investigated naturally acquired transmission-blocking immunity (TBI) against Plasmodium vivax, a major malaria parasite. METHODS: Using the direct membrane-feeding assay, we assessed TBI in plasma samples and examined the role of antibodies by removing immunoglobulins through protein G/L adsorption before mosquito feeding. Strain specificity was evaluated by conducting a direct membrane-feeding assay with plasma exchange. RESULTS: Blood samples from 47 patients with P vivax were evaluated, with 37 plasma samples successfully infecting mosquitoes. Among these, 26 showed inhibition before immunoglobulin depletion. Despite substantial immunoglobulin removal, 4 samples still exhibited notable inhibition, while 22 had reduced blocking activity. Testing against heterologous strains revealed some plasma samples with broad TBI and others with strain-specific TBI. CONCLUSIONS: Our findings indicate that naturally acquired TBI is mainly mediated by antibodies, with possible contributions from other serum factors. The transmission-blocking activity of plasma samples varied by the tested parasite strain, suggesting single polymorphic or multiple targets for naturally acquired TBI. These observations improve understanding of immunity against P vivax and hold implications for transmission-blocking vaccine development.

Sequence Data From a Travel-Associated Case of Microcephaly Highlight a Persisting Risk due to Zika Virus Circulation in Thailand.

Zika virus has been circulating in Thailand since 2002 through continuous but likely low-level circulation. Here, we describe an infection in a pregnant woman who traveled to Thailand and South America during her pregnancy. By combining phylogenetic analysis with the patient's travel history and her pregnancy timeline, we confirmed that she likely got infected in Thailand at the end of 2021. This imported case of microcephaly highlights that Zika virus circulation in the country still constitutes a health risk, even in a year of lower incidence. MAIN POINTS: Here we trace the origin of travel-acquired microcephaly to Thailand, providing additional evidence that pre-American lineages of Zika virus can harm the fetus and highlighting that Zika virus constitutes a health threat even in a year of lower incidence.

Inadvertent Platelet Transfusion from Monkeypox Virus-Infected Donor to Recipient, Thailand, 2023.

In Thailand, platelet product from a blood donor was transfused to a recipient who had dengue. Two days later, the donor was confirmed to have monkeypox virus infection. Monkeypox virus DNA was undetectable in recipient specimens up to 2 weeks after transfusion. The recipient remained asymptomatic at 4 weeks of monitoring.

Melioidosis in Patients with COVID-19 Exposed to Contaminated Tap Water, Thailand, 2021.

In September 2021, a total of 25 patients diagnosed with COVID-19 developed acute melioidosis after (median 7 days) admission to a COVID-19 field hospital in Thailand. Eight nonpotable tap water samples and 6 soil samples were culture-positive for Burkholderia pseudomallei. Genomic analysis suggested contaminated tap water as the likely cause of illness.

Acute Gastroenteritis Associated with Norovirus GII.8[P8], Thailand, 2023.

Acute gastroenteritis associated with human norovirus infection was reported in Phuket, Thailand, in June 2023. We amplified GII.8[P8] from the outbreak stool specimens. Retrospective sample analysis identified infrequent GII.8[P8] in the country beginning in 2018. In all, the 10 whole-genome GII.8[P8] sequences from Thailand we examined had no evidence of genotypic recombination.

The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand.

Thailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER-LC consortium-based population study covering all high-incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011-2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06-2.11 to 2.91; 95% CI: 1.82-4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64-0.96) and iCCA (HR 0.84; 95% CI: 0.70-0.99). Risk factor co-exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer-term survivors, including behavioral changes to reduce exposures.

Prevalence and dynamics of antimalarial drug resistance mutations among the Plasmodium falciparum isolates in TAK Province, Thailand, during the period of 1998-2001.

Despite the overall decline in malaria cases in Thailand, continuous surveillance in endemic areas remains crucial. This retrospective analysis examined Plasmodium falciparum samples from Tak province, Thailand, collected in 1998, 1999, and 2001, to investigate the prevalence and evolution of antimalarial genotypic drug resistance. The study revealed a high prevalence of drug-resistant P. falciparum, particularly to mefloquine and sulfadoxine/pyrimethamine, with significant mutations in genes associated with resistance. Notably, mutations indicative of artemisinin resistance, such as those in the kelch13 gene, were detected at low frequencies, suggesting an evolving resistance pattern. The underlying cause of these resistance mutations appears to be the historical and widespread use of these antimalarial drugs, which exerted selective pressure on the parasite population. These findings underscore the necessity of ongoing surveillance and adaptive control strategies to manage drug resistance, guide treatment policies, and prevent potential outbreaks, even as malaria cases decrease. Continuous monitoring and research are imperative to sustain malaria elimination efforts and address the dynamic challenges posed by evolving drug-resistant strains.

Framingham risk score based vascular outcomes in acute versus chronic HIV cohorts after 6 years of ART.

INTRODUCTION: Immune dysregulation persists in people with HIV (PWH) on antiretroviral therapy (ART) and may lead to accelerated vascular ageing and cardiovascular disease (CVD). While delayed time to initiation of ART has been linked to worse cardiovascular outcomes, the effect of ART initiation during acute infection on these outcomes is not well understood. METHODS: Participants were enrolled from the SEARCH010/RV254 acute HIV (AHI) and HIV-NAT chronic HIV (CHI) cohorts in Thailand. Participants with 6-year follow-up and viral suppression (viral load < 50 copies/µL) at follow-up were included. Both unmatched cohorts and age and gender-matched cohorts were analysed. Demographics, HIV laboratories, and cardiovascular risk factors from enrolment and 6-year follow-up were obtained from electronic records. Framingham Risk Score (FRS), vascular age (VA), vascular age deviation (VAD), and 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated from previously published equations. Vascular outcomes in AHI and CHI cohorts were compared, and univariable and multivariable linear regression analyses were used to investigate risk factors associated with worse vascular scores. RESULTS: In all, 373 AHI participants and 608 CHI participants were identified. AHI participants were of younger age, had a higher prevalence of syphilis and a lower prevalence of prior hepatitis B, tuberculosis, diabetes, and hypertension. Higher CD4 T-cell and lower CD8 T-cell counts were seen in the AHI cohort at enrolment and 6-year follow-up. In all participants, the AHI cohort had a lower median FRS (p < 0.001) and VA (p < 0.001), but higher VAD (p < 0.001). However, in matched cohorts, no differences were found in FRS-based outcomes. In all participants, higher VAD after 6 years of ART was associated with higher body mass index (p < 0.001) and higher CD4 count (p < 0.001), which persisted in multivariable analysis. When FRS components were analysed individually, CD4 count was associated only with male sex and cholesterol. CONCLUSIONS: We did not identify differences in FRS-based vascular outcomes at 6 years in matched cohorts of participants who started ART during AHI versus CHI. We identified a correlation between higher CD4 count and worse FRS-based vascular outcomes, which may be driven by underlying metabolic risk factors. Further study is needed to confirm these findings and evaluate underlying mechanisms.

High prevalence of ESBL-producing E. coli phylogroup B2 clinical isolates in northeastern Thailand.

BACKGROUND: Production of extended-spectrum ß-lactamases (ESBLs) is a common resistance mechanism in Enterobacteriaceae, leading to serious hospital-acquired infections. This study aimed to assess phenotypic, phylogenetic, and antibiotic resistance patterns among ESBL-producing Escherichia coli isolates recovered from two rural tertiary hospitals in Thailand. RESULTS: Among 467 Enterobacteriaceae isolates, E. coli was the most prevalent 356 (76.2%) followed by K. pneumoniae 88 (18.8%), K. aerogenes 8 (1.7%), K. variicola 3 (0.6%), K. quasipneumoniae 1 (0.2%%), K. oxytoca 1 (0.2%), and unidentified 9 (1.9%). Of the 202 cephalosporin-resistant E. coli isolates, 195 (96.5%) were ESBL-producing and 7 (3.5%) were non-ESBL-producing. Clermont typing revealed that phylogroup B2 was predominant (43.3%), followed by phylogroups F (11.3%), D (10.3%), C (9.7%), and A (8.7%). Among the beta-lactamase-encoding genes, blaCTX-M (83.6%) and blaTEM (81.0%) were widely found among the isolates, and blaCTX-M-1 (60.7%) was the most common among the five blaCTX-M subgroups detected. The predominant ESBL was blaCTX-M-15 (58.3%). All isolates were resistant to cefotaxime (100%) and ampicillin (100%), followed by ciprofloxacin (91.3 %), ceftazidime (72.8 %), and tetracycline (64.1%). CONCLUSION: Our findings show that phylogroup B2 was the most prevalent phylogroup among ESBL-producing E. coli isolates in northeastern Thailand. Notably, the isolates mostly carried the blaCTX-M gene(s).

A simple nomogram to predict dengue shock syndrome: A study of 4522 south east Asian children.

Dengue shock syndrome (DSS) substantially worsens the prognosis of children with dengue infection. This study aimed to develop a simple clinical tool to predict the risk of DSS. A cohort of 2221 Thai children with a confirmed dengue infection who were admitted to King Chulalongkorn Memorial Hospital between 1987 and 2007 was conducted. Another data set from a previous publication comprising 2,301 Vietnamese children with dengue infection was employed to create a pooled data set, which was randomly split into training (n = 3182), testing (n = 697) and validating (n = 643) datasets. Logistic regression was compared to alternative machine learning algorithms to derive the most predictive model for DSS. 4522 children, including 899 DSS cases (758 Thai and 143 Vietnamese children) with a mean age of 9.8 ± 3.4 years, were analyzed. Among the 12 candidate clinical parameters, the Bayesian Model Averaging algorithm retained the most predictive subset of five covariates, including body weight, history of vomiting, liver size, hematocrit levels, and platelet counts. At an Area Under the Curve (AUC) value of 0.85 (95% CI: 0.81-0.90) in testing data set, logistic regression outperformed random forest, XGBoost and support vector machine algorithms, with AUC values being 0.82 (0.77-0.88), 0.82 (0.76-0.88), and 0.848 (0.81-0.89), respectively. At its optimal threshold, this model had a sensitivity of 0.71 (0.62-0.80), a specificity of 0.84 (0.81-0.88), and an accuracy of 0.82 (0.78-0.85) on validating data set with consistent performance across subgroup analyses by age and gender. A logistic regression-based nomogram was developed to facilitate the application of this model. This work introduces a simple and robust clinical model for DSS prediction that is well-tailored for children in resource-limited settings.

Unusual G3P[10] bat-like rotavirus strains detected in children with acute gastroenteritis in Thailand.

Rotavirus A (RVA) is the main cause of acute gastroenteritis among children under the age of five globally. The unusual bat-like human RVA strains G3P[10] (RVA/Human-wt/THA/CMH079/05/2005/G3P[10] and RVA/Human-wt/THA/CMH-S015-19/2019/G3P[10]) were detected in children with acute gastroenteritis in 2005 and 2019, respectively, in the same geographical area of Northern Thailand. To elucidate the genetic backgrounds of these unusual or bat-like human RVA strains, the complete genome of these RVA strains was sequenced and phylogenetically analyzed. All eleven genome segments of these G3P[10] strains were genotyped as G3-P[10]-I8-R3-C3-M3-A9-N3-T3-E3-H6, which is closely related to bat G3P[10] RVA strain (RVA/Bat-tc/CHN/MYAS33/2013/G3P[10]) and bat-like human RVA strain (RVA/Human-wt/THA/MS2015-1-0001/2015/G3P[10]). The findings indicate that human G3P[10] RVA strains detected in this study (RVA/Human-wt/THA/CMH079/05/2005/G3P[10] and RVA/Human-wt/THA/CMH-S015-19/2019/G3P[10]) contained all eleven genome segments similar to those of bat RVA strains and appeared to be human RVA strains of bat origin. Phylogenetic analysis revealed that several genome segments of these two RVA strains were also closely related with those of other species in addition to bats and had a zoonotic transmission history. The results of this study supported the roles of interspecies transmission of RVA strains among bats and humans in the natural environment and provided convincing evidence that the evolution of human RVAs was closely interrelated with those of animal RVAs. Continuing surveillance of RVAs in humans and animals is imperative to gain a better understanding of the origin and the evolution of these viruses.

Dengue virus transmission risk in blood donation: Evidence from Thailand.

Individuals infected with dengue virus (DENV) often show no symptoms, which raises the risk of DENV transfusion transmission (TT-DENV) in areas where the virus is prevalent. This study aimed to determine the evidence of DENV infection in blood donors from different geographic regions of Thailand. A cross-sectional study was conducted on blood donor samples collected from the Thai Red Cross National Blood Center and four regional blood centers between March and September 2020. Screening for DENV nonstructural protein 1 (NS1), anti-DENV immunoglobulin G (IgG), and IgM antibodies was performed on residual blood from 1053 donors using enzyme-linked immunosorbent assay kits. Positive NS1 and IgM samples indicating acute infection were verified using four different techniques, including quantitative real-time (q) RT-PCR, nested PCR, virus isolation in C6/36 cells, and mosquito amplification. DENV IgG seropositivity was identified in 89% (938/1053) of blood donors. Additionally, 0.4% (4/1053) and 2.1% (22/1053) of Thai blood donors tested positive for NS1 and IgM, respectively. The presence of asymptomatic dengue virus infection in healthy blood donors suggests a potential risk of transmission through blood transfusion, posing a concern for blood safety.

Epidemiology of hip fractures in Thailand.

This retrospective study examining hip fracture incidence, hip fracture trends, and the annual hospitalization costs for hip fractures in a population aged 50 years and older within the Universal Health Coverage System revealed that the incidence of hip fractures and the annual hospitalization costs for hip fractures increased significantly from 2013 to 2022. PURPOSE: To examine the annual incidence of hip fractures over 10 years (2013-2022), hip fracture trends, and the annual hospitalization costs for hip fractures in a population aged 50 years and older within the Universal Health Coverage System. METHODS: A retrospective study was conducted. Hip fracture hospitalizations were identified using ICD-10. Data on the number of hip fracture hospitalizations, population aged ≥ 50 years, and hospitalization costs were obtained. The primary outcome was the annual incidence of hip fractures. The secondary outcomes were hip fracture incidence by 5-year age group, the annual hospitalization costs for hip fractures, and the number of hip fractures in 6 regions of Thailand. RESULTS: The hip fracture incidence increased annually from 2013-2019 and then plateaued from 2019-2022, with the crude incidence (per 100,000 population) increasing from 112.7 in 2013 to 146.7 in 2019 and 146.9 in 2022. The age-standardized incidence (per 100,000 population) increased from 116.3 in 2013 to 145.1 in 2019 and remained at 140.7 in 2022. Increases in the crude incidence were observed in both sexes (34% in females and 21% in males; p < 0.05). The annual hospitalization costs for hip fractures increased 2.5-fold, from 17.3 million USD in 2013 to 42.8 million USD in 2022 (p < 0.001). The number of hip fractures increased in all six regions of Thailand across the 10-year study period. CONCLUSION: Osteoporotic hip fractures are a significant health concern in Thailand. The incidence and the annual hospitalization costs for hip fractures increased significantly from 2013 to 2022.

Partying in Thailand: Never Testing Among Men Who Have Sex With Men Who Attend Sexualized (Drug) Parties.

BACKGROUND: Human immunodeficiency virus (HIV) testing for Thai men who have sex with men (MSM) is suboptimal, which undermines their linkage to care and subsequent HIV preexposure prophylaxis (PrEP) uptake. METHODS: We analyzed a cross-sectional survey conducted in 2021 among Thai MSM who attended any private sex parties or circuit parties in the past 3 years ("sexualized parties"). RESULTS: Of the 424 men included in our analysis, 47.6% had been recently tested for HIV in the past 1 year, 30.2% had not recently been tested, and 22.2% had never been tested. In our multivariable analysis, relative to participants who had recently tested for HIV, those who have never tested were more likely to have lower education or to live outside of Bangkok, and to have attended both circuit and private sex parties (vs. private sex party only) but were less likely to report any sexually transmitted infection diagnosis or to have heard of PrEP. Participants who had an HIV test more than a year ago were more likely to have attended both circuit and private sex parties (vs. private sex parties only) but were less likely to have any sexually transmitted infection diagnosis, meet sexual partners online, or have heard of PrEP. Rates of condomless anal sex and willingness to use PrEP were similar across groups. CONCLUSIONS: Despite the high rates of sexual risk-taking, sexualized party attendees reported suboptimal HIV testing uptake. The joint promotion of HIV testing and PrEP is warranted-especially on-premise HIV testing at circuit parties and outreach at online platforms to reach sexualized party attendees.

Comparative effectiveness analysis of survival with first-line palbociclib or ribociclib plus AI in HR + /HER2- advanced breast cancer (CEPRA study): preliminary analysis of real-world data from Thailand.

BACKGROUND: The current standard first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR + /HER2 -) advanced breast cancer (ABC) is a combination of aromatase inhibitor (AI) plus CDK4/6 inhibitors (CDK4/6i). Direct comparison trials of different CDK4/6i are scarce. This real-world study compared the effectiveness of first-line AI plus ribociclib versus palbociclib. METHODS: This multicenter retrospective cohort study, conducted in six cancer centers in Thailand, enrolled patients with HR + /HER2 - ABC treated with first-line AI, and either ribociclib or palbociclib. Propensity score matching (PSM) was performed. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), time to chemotherapy (TTC), and adverse events. RESULTS: Of the 250 patients enrolled, 134 patients with ribociclib and 49 patients with palbociclib were captured after PSM. Baseline characteristics were well-balanced between groups. Median PFS in patients receiving ribociclib and palbociclib were 27.9 and 31.8 months, respectively (hazard ratio: 0.87; 0.55-1.37). The median OS in the AI + ribociclib arm was 48.7 months compared to 59.1 months in the AI + palbociclib arm (hazard ratio: 0.55; 0.29-1.05). The median TTC in the AI + palbociclib group was 56 months, but not reached in the AI + ribociclib group (p = 0.42). The ORR of AI + ribociclib and AI + palbociclib were comparable (40.5% vs. 53.6%, p = 0.29). Patients receiving palbociclib demonstrated a higher proportion of neutropenia compared to those receiving ribociclib, despite a similar dose reduction rate (p = 0.28). Hepatitis rate was similar between the ribociclib (21%) and palbociclib groups (22%). Additionally, a low incidence of QT prolongation was observed in both the ribociclib (5%) and palbociclib groups (4%). CONCLUSION: This preliminary analysis of a real-world study demonstrated the comparable effectiveness of ribociclib and palbociclib with AI as an initial therapy for HR + /HER2 - ABC. No statistically significant difference in PFS, OS, and TTC was found in patients treated with AI combined with palbociclib or ribociclib. Longer follow-up and further prospective randomized head-to-head studies are warranted.

Diabetes and risk of hospitalisation due to infection in northeastern Thailand: Retrospective cohort study using population-based healthcare service data.

BACKGROUND: Population-based studies describing the association between diabetes and increased risk of infection have largely been based in high-income countries. There is limited information describing the burden of infectious disease attributable to diabetes in low and middle-income countries. This study aimed to describe the burden and risk of infectious disease hospitalisation in people with diabetes compared to those without diabetes in northeastern Thailand. METHODS: In a retrospective cohort study using electronic health record data for 2012-2018 for 3.8 million people aged ≥20 years in northeastern Thailand, hospitalisation rates for any infectious diseases (ICD-10 codes A00-B99) were estimated and negative binomial regression used to estimate rate ratios (RR) for the association between diabetes and infectious disease hospitalisation adjusted for age, sex and area of residence. RESULTS: In this study, 164,177 people had a diagnosis of diabetes mellitus at any point over the study period. Infectious disease hospitalisation rates per 1000 person-years (95%CI) were 71.8 (70.9, 72.8), 27.7 (27.1, 28.3) and 7.5 (7.5, 7.5) for people with prevalent diabetes, incident diabetes and those without diabetes respectively. Diabetes was associated with a 4.6-fold higher risk of infectious disease hospitalisation (RR (95% CI) 4.59 (4.52, 4.66)). RRs for infectious disease hospitalisation were 3.38 (3.29, 3.47) for people with diabetes managed by lifestyle alone and 5.29 (5.20, 5.39) for people receiving prescriptions for diabetes drugs. CONCLUSIONS: In this Thai population, diabetes was associated with substantially increased risk of hospitalisation due to infectious diseases and people with diabetes who were on pharmacological treatment had a higher risk than those receiving lifestyle modification advice alone.