Causal mediation analyses for the natural course of hepatitis C: a prospective cohort study.

BackgroundHepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.MethodsA community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants' serum samples. The cohort data were linked to Taiwan's National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases.ResultsIn 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect.ConclusionBoth intrahepatic and extrahepatic manifestations mediated approximately a half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.

Effects of personalized music listening on post-stroke cognitive impairment: A randomized controlled trial.

BACKGROUND AND PURPOSE: Previous studies have suggested that music listening has the potential to positively affect cognitive functions and mood in individuals with post-stroke cognitive impairment (PSCI), with a preference for self-selected music likely to yield better outcomes. However, there is insufficient clinical evidence to suggest the use of music listening in routine rehabilitation care to treat PSCI. This randomized control trial (RCT) aims to investigate the effects of personalized music listening on mood improvement, activities of daily living (ADLs), and cognitive functions in individuals with PSCI. MATERIALS AND METHODS: A total of 34 patients with PSCI were randomly assigned to either the music group or the control group. Patients in the music group underwent a three-month personalized music-listening intervention. The intervention involved listening to a personalized playlist tailored to each individual's cultural, ethnic, and social background, life experiences, and personal music preferences. In contrast, the control group patients listened to white noise as a placebo. Cognitive function, neurological function, mood, and ADLs were assessed. RESULTS: After three months of treatment, the music group showed significantly higher Montreal Cognitive Assessment (MoCA) scores compared to the control group (p=0.027), particularly in the domains of delayed recall (p=0.019) and orientation (p=0.023). Moreover, the music group demonstrated significantly better scores in National Institutes of Health Stroke Scale (NIHSS) (p=0.008), Barthel Index (BI) (p=0.019), and Zarit Caregiver Burden Interview (ZBI) (p=0.008) compared to the control group. No effects were found on mood as measured by the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). CONCLUSION: Personalized music listening promotes the recovery of cognitive and neurological functions, improves ADLs, and reduces caregiver burden in patients with PSCI.

Proactive M2 Blockade Prevents Cognitive Decline in GRK5-Deficient APP Transgenic Mice via Enhancing Cholinergic Neuronal Resilience.

Alzheimer's disease (AD) poses an immense challenge in healthcare, lacking effective therapies. This study investigates the potential of AAD23, a selective M2 receptor antagonist, in proactively preventing cognitive impairments and cholinergic neuronal degeneration in GRK5-deficient Swedish APP (GAP) mice. GAP mice manifest cognitive deficits by 7 months and develop senile plaques (SPs) by 9 months. A six-month AAD23 treatment was initiated at 5 months and stopped at 11 months before behavioral assessments without the treatment. AAD23-treated mice exhibited preserved cognitive abilities and improved cholinergic axonal health in the nucleus basalis of Meynert (NBM) akin to wild-type mice. Conversely, vehicle-treated GAP mice displayed memory deficits and pronounced cholinergic axonal swellings in the NBM. Notably, AAD23 treatment did not alter SPs and microgliosis. These findings highlight AAD23's efficacy in forestalling AD-related cognitive decline in GRK5-deficient subjects, attributing its success to restoring cholinergic neuronal integrity and resilience, enhancing resistance against diverse degenerative insults.

Patient Experience with Chronic Refractory Gout and Its Impact on Health-Related Quality of Life: Literature Review and Qualitative Analysis.

INTRODUCTION: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL). METHODS: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population. RESULTS: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants. CONCLUSIONS: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.

The extent of interruptions to primary care medical officers' consultations in the Western Cape.

BACKGROUND:  Administrative tasks are an increasing burden for primary care doctors globally and linked to burnout. Many tasks occur during consultations. They cause interruptions with possible effects on patients' and doctors' experiences and care. The burden and typology of interruptions of doctors in primary care consultations have not been studied in South Africa. Given the link between administrative loads and burnout, describing the extent of these interruptions would help. This study's aim was to assess the extent of interruptions on primary care doctors in the Western Cape. METHODS:  This was a descriptive cross-sectional survey. Doctors from rural and urban primary care clinics in the Western Cape answered an online self-administered survey on the types of interruptions experienced during consultations. Interruptions were categorised and their prevalence calculated. Clinical and non-clinical interruption categories were compared. RESULTS:  There were 201 consultations from 30 doctors. Most interruptions were from retrieving and recording the current patient's information (93.0%), paperwork for other patients (50.7%), and telephone calls about the current patient (41.8%). Other prevalent interruptions were for emergencies (39.8%) and acquiring consumables (37.3%). The median (interquartile range [IQR]) of four (2-4) interruption types per consultation was higher than global settings. CONCLUSION:  Doctors experienced many interruptions during consultations. Their wide range included interruptions unrelated to the current patient.Contribution: This study adds insights from the global south on clinicians' administrative burden. It elaborates on the types of activities that interrupt consultations in an upper-middle income primary care setting. Exploration of interventions to decrease this burden is suggested.

Economic burden of suicides and suicide attempts in low- and middle-income countries: a systematic review of costing studies.

INTRODUCTION: Suicide is a major public health concern in low- and middle-income countries (LMICs) due to its substantial psychological, social, and economic impact. There is little synthesized evidence to estimate the economic burden of suicide and suicide attempts in such economies. The present systematic literature review aims to examine existing evidence on the cost of illness (COI) in the case of suicides and suicide attempts and assess their quality. METHODS: A systematic review was carried out using electronic databases, such as Medline, EMBASE, EconLit, PsycINFO, and CINAHL using keywords like 'suicide and suicide attempts,' 'cost of illness,' and economic burden." The quality assessment of studies was conducted along with the per-person cost estimation to understand the variation of methods followed across the studies. RESULT: 14 studies qualified for final data extraction and synthesis out of 4,164 studies. The studies showed heterogeneity across objectives, settings, and methods, with cost estimates reflecting a wide range of costings per person in suicide and suicide attempts. CONCLUSION: It is challenging to determine and compare the economic estimates of suicide. Intensive research is warranted with standardized cost assessment techniques and wider perspectives to understand the true economic burden of suicide. REGISTRATION: PROSPERO Registration No- CRD42022294080.

The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Histopathological, Molecular and Clinical Profiling of Lymphoepithelioma-Like Carcinoma of the Bladder (LELC-B).

Lymphoepithelioma-like urothelial carcinoma of the urinary bladder (LELC-B) is a rare histologic subtype characterized by strong immune cell infiltrates. A better prognosis and favorable response rates to immune-checkpoint inhibitors (ICI) have been described. We aimed to characterize the molecular profiles and immune cell infiltration of LELC-B for a better understanding and its therapeutic implications. We identified eleven muscle-invasive bladder cancer cases with pure and mixed LELC-B. PD-L1 expression and mismatch-repair (MMR) proteins were evaluated using immunohistochemistry. We calculated the tumor-mutational burden (TMB) and characterized mutational profiles using whole exome DNA-sequencing data. Transcriptomic signatures were detected using the NanoString nCounter PanCancer IO360 panel. Multiplex immunofluorescence of tumor microenvironment (PD-L1, PanCK, aSMA, Vimentin, CD45, Ki67) and T-cells (CD4, CD3, PD-1, CD163, CD8, FoxP3) was used to quantify cell populations. All LELC-B cases were highly positive for PD-L1 (median TPS/TC 70%; range 20-100; median CPS 100; range 50-100), MMR-proficient and negative for Epstein-Barr virus infection. Immune cell infiltrates were characterized by high CD8+ T-cell count and high PD-1/PD-L1 expression on immune and tumor cells. LELC-B showed upregulation of signaling pathways involved in immune cell response. Most common mutations were found in chromatin remodeling genes causing epigenetic dysregulation. All LELC-B cases showed high TMB of 39 Mut/Mb (IQR 29-66). In conclusion, LELC-B is a highly immunogenic tumor, showing strong upregulation of PD1/PD-L1 and making ICI a promising treatment option.

Approved treatments for neovascular age-related macular degeneration: current safety and future directions.

INTRODUCTION: Age-related macular degeneration (AMD) is a progressive retinal degenerative disease that is implicated as one of the leading causes of visual impairment in the elderly population. Vascular endothelial growth factor (VEGF) has been identified as the main driver of AMD, and various therapeutics have revolutionized the treatment and management of neovascular AMD (nAMD) with favorable visual and anatomical outcomes. AREAS COVERED: Physicians have a variety of approved therapeutics in their arsenal for patients with varying disease progression and patient-specific needs, with the ultimate goal of achieving optimal visual and anatomic outcomes. The literature search was conducted using PubMed, Google Scholar, and sources from companies' websites, allowing us to locate findings recently presented at conferences. EXPERT OPINION: Scientific advancements in the field have led to newly approved therapeutics and devices, such as the port-delivery system with ranibizumab (PDS), and further investigation is ongoing in the realm of gene therapy for retinal diseases. In addition to efficacy and durability, newer agents must have comparable safety profiles to older agents in order to be used broadly. These options introduce a level of complexity in nAMD treatment; however, physicians to personalize treatment to improve vision in nAMD patients and reduce treatment burden overall.

The CAREPAL-8: a short screening tool for multidimensional family caregiver burden in palliative care.

BACKGROUND: Family caregivers of terminally ill and dying people do not only experience varying levels but also different dimensions of caregiver-related strain and burden. The aim of the study was to develop a short multidimensional screening tool for the detection of burden in family caregivers in palliative care. METHODS: Family caregivers of cancer patients newly admitted to specialist inpatient palliative care (N = 232) completed questionnaires on psychological burden, quality of life, social support and need fulfillment. A latent class mixture model was used to identify discrete classes of family caregivers related to their multidimensional caregiver burden. Multinomial logistic regression analyses were performed to identify the most predictive items from a set of established questionnaires. RESULTS: Four latent classes of family caregivers were identified: Currently stable caregivers (37%), Caregivers with unmet needs (20%), Psychologically burdened caregivers (30%), and High-risk caregivers (13%). Each of these classes describes a different risk profile of multidimensional family caregiver burden, although family caregivers exhibit high levels of distress across all classes. From a set of 48 items, we identified eight items that predicted the class membership best. These items represent the items of the novel multidimensional screening tool: The 8-item Screening Tool for Family Caregiver Burden in Palliative Care (CAREPAL-8). Except for social support, the items maintained fidelity to the conceptualization of multidimensional caregiver burden used in this study. A preliminary classification system was developed, which has yet to be validated. CONCLUSIONS: This study represents the first step in the establishment of a practical, self-administered screening tool that might help healthcare providers to tailor caregiver care according to their burden in daily practice. Brevity of the 8-item tool might facilitate its use in routine clinical care.

Change in the global burden of depression from 1990-2019 and its prediction for 2030.

OBJECTIVE: Depression is a global health challenge, but only a few studies have fully assessed and predicted the disease burden. This study described the trend of global depression burden from 1990 to 2019 through age-standardized incidence rate (ASIR), age-standardized disability-adjusted life rate (ASDR), and predicted the number of cases of depression during 2020-2030. METHODS: Linear regression analysis was used to calculate the estimated annual percentage change (EAPC) in the age-standardized rates. The trends of global depression burden from 1990 to 2019 were analyzed by age, sex, and socio-demographic index (SDI) across various regions. Finally, we used the Bayesian age-period-cohort (BAPC) model to predict the disease burden in the coming 10 years. RESULTS: Globally, the ASIR of depression decreased from 3681.24 per 100,000 population in 1990 to 3588.25 per 100,000 population in 2019 and the EAPC was -0.29%. ASDR also decreased, following a similar trend as the ASIR. The highest ASDR was observed in adults aged 60-64 years. The burden of depressive illness was higher in women, with the greatest increase in incidence in low SDI areas. BAPC predicted that the worldwide ASIR and ASDR of depression would stabilize from 2020 to 2030, with an increasing number of cases. By 2030, the ASIR was estimated to be 2519.88 per 100,000 men and 3835.11 per 100,000 women. CONCLUSION: From 1990 to 2019, the global burden of depression remained significant, especially among women. It is important to address depression in older people, and it is therefore necessary to develop measures for prevention.

Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.

BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.

Estimation of Attributable Risk and Direct Medical and Non-Medical Costs of Major Mental Disorders Associated With Air Pollution Exposures Among Children and Adolescents in the Republic of Korea, 2011-2019.

BACKGROUND: Recent studies have reported the burden of attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and depressive disorder. Also, there is mounting evidence on the effects of environmental factors, such as ambient air pollution, on these disorders among children and adolescents. However, few studies have evaluated the burden of mental disorders attributable to air pollution exposure in children and adolescents. METHODS: We estimated the risk ratios of major mental disorders (ADHD, ASD, and depressive disorder) associated with air pollutants among children and adolescents using time-series data (2011-2019) obtained from a nationwide air pollution monitoring network and healthcare utilization claims data in the Republic of Korea. Based on the estimated risk ratios, we determined the population attributable fraction (PAF) and calculated the medical costs of major mental disorders attributable to air pollution. RESULTS: A total of 33,598 patients were diagnosed with major mental disorders during 9 years. The PAFs for all the major mental disorders were estimated at 6.9% (particulate matter < 10 µm [PM10]), 3.7% (PM2.5), and 2.2% (sulfur dioxide [SO2]). The PAF of PM10 was highest for depressive disorder (9.2%), followed by ASD (8.4%) and ADHD (5.2%). The direct medical costs of all major mental disorders attributable to PM10 and SO2 decreased during the study period. CONCLUSION: This study assessed the burden of major mental disorders attributable to air pollution exposure in children and adolescents. We found that PM10, PM2.5, and SO2 attributed 7%, 4%, and 2% respectively, to the risk of major mental disorders among children and adolescents.

Randomized, open-label, phase 2 study of nivolumab plus ipilimumab or nivolumab monotherapy in patients with advanced or metastatic solid tumors of high tumor mutational burden.

BACKGROUND: Checkpoint inhibitor therapy has demonstrated overall survival benefit in multiple tumor types. Tumor mutational burden (TMB) is a predictive biomarker for response to immunotherapies. This study evaluated the efficacy of nivolumab+ipilimumab in multiple tumor types based on TMB status evaluated using either tumor tissue (tTMB) or circulating tumor DNA in the blood (bTMB). PATIENTS AND METHODS: Patients with metastatic or unresectable solid tumors with high (≥10 mutations per megabase) tTMB (tTMB-H) and/or bTMB (bTMB-H) who were refractory to standard therapies were randomized 2:1 to receive nivolumab+ipilimumab or nivolumab monotherapy in an open-label, phase 2 study (CheckMate 848; NCT03668119). tTMB and bTMB were determined by the Foundation Medicine FoundationOne® CDx test and bTMB Clinical Trial Assay, respectively. The dual primary endpoints were objective response rate (ORR) in patients with tTMB-H and/or bTMB-H tumors treated with nivolumab+ipilimumab. RESULTS: In total, 201 patients refractory to standard therapies were randomized: 135 had tTMB-H and 125 had bTMB-H; 82 patients had dual tTMB-H/bTMB-H. In patients with tTMB-H, ORR was 38.6% (95% CI 28.4% to 49.6%) with nivolumab+ipilimumab and 29.8% (95% CI 17.3% to 44.9%) with nivolumab monotherapy. In patients with bTMB-H, ORR was 22.5% (95% CI 13.9% to 33.2%) with nivolumab+ipilimumab and 15.6% (95% CI 6.5% to 29.5%) with nivolumab monotherapy. Early and durable responses to treatment with nivolumab+ipilimumab were seen in patients with tTMB-H or bTMB-H. The safety profile of nivolumab+ipilimumab was manageable, with no new safety signals. CONCLUSIONS: Patients with metastatic or unresectable solid tumors with TMB-H, as determined by tissue biopsy or by blood sample when tissue biopsy is unavailable, who have no other treatment options, may benefit from nivolumab+ipilimumab. TRIAL REGISTRATION NUMBER: NCT03668119.

Balancing the benefits and risks of China's national salt iodization policy over 30 years using disability-adjusted life years (DALYs): a systematic review and meta-analysis.

Both insufficient and excessive iodine intake can lead to thyroid-related disorders. Although China has made progress in eliminating iodine deficiency over the past few decades, the incidence of thyroid cancer is increasing. Currently, there is a lack of relevant research on the tradeoff between the benefits and risks of salt iodization in China. In this study, we developed a method that combines the total probability algorithm and disease burden to evaluate the appropriate amount of salt iodization. Following the principle of minimizing the comprehensive disease burden and using the metabolic model of human iodine nutrition. Based on the average national iodine level in water, the optimal iodine content in Chinese salt is determined to be 17 mg/kg. However, iodine content in water is not evenly distributed in China. Approximately 3.23% of administrative villages have water iodine concentrations exceeding 80 ug/L, eliminating the need for iodine fortification in salt. Approximately 83.51% of administrative villages need to continue implementing the salt iodization policy, with the optimal iodine content in salt ranging from 15 to 18 mg/kg. In 13.16% of administrative villages, the iodine content in salt is determined based on the local water iodine concentration, ranging from 0 to 15 mg/kg. Our study cracks open a window of insight suggesting that the optimal iodine content for salt is lower than the existing benchmark dictated by the prevailing policy in China. Hence, there is an urgent need to refine and advance the iodine supplementation strategy in salt to pave the way for precision medicine and health-centric iodine supplementation strategies.

Evaluation of viral suppression and medication-related burden among HIV-infected adults in a secondary care facility.

Background: People living with HIV/AIDS (PLHIV) are prone to other health issues that may result from the disease or antiretroviral medicines. These persons experience other psychosocial aspects of the illness, which may negatively affect their quality of life and overall treatment outcomes. This study assessed the medication-related burden and virological response of adult PLHIV. Method: This cross-sectional study involved 417 HIV-positive adults who had been on combined antiretroviral therapy for at least a year at the State Specialist Hospital Gombe. Nigeria. Patient medication experience was measured using the Living with Medication Questionnaire version-3 (LMQ-3). Virological suppression was assessed at viral loads <1000 copies/ml and 20 copies/ml for undetectable HIV RNA levels. The LMQ-3 scores were compared with the participants' characteristics using independent t-tests or one-way analysis of variance (ANOVA). Regression analyses was employed to identify the predictors of viral suppression and medication-related burden. P value <0.05 at 95% confidence interval was considered statistically significant. Results: Of the 417 PLHIV included in this study, 271 (65%) were classified as WHO Stage 1 ART initiation, 93.8% achieved viral suppression with 291 (69.5%) whom were females. The majority of patients 382 (91.6%) were on a dolutegravir-based regimen, had no tuberculosis diagnosis at antiretroviral therapy (ART) initiation (82.5%) and were 6-10 years on ART (46.3%). Only 67.6% of the population had a moderate medication-related burden. Female sex (p < 0.0005), unsuppressed viral load (p = 0.01), second-line ART (p = 0.03), tuberculosis at ART initiation (p = 0.02), and employment (p = 0.003) were significantly associated with medication-related burden. The predictor of viral suppression was high degree of medication-related burden (AOR, 0.12; 95% CI, 0.02-0.59) while unsuppressed viral load (p = 0.01) and female gender (p = 0.002) were independent predictors of medication related burden. Conclusion: The findings from this study revealed that majority of the patients achieved viral suppression with moderate degree of medication-related burden. Targeted interventions should be directed toward younger patients, females and patients with unsuppressed viral loads.

Trends in three malnutrition factors in the global burden of disease: iodine deficiency, vitamin A deficiency, and protein-energy malnutrition (1990-2019).

Background: Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition are prevalent malnutrition issues that disproportionately affect low-income countries and pose significant risks to the health and development of children and adolescents. This study offers a detailed examination of these deficiencies' prevalence trends and gender and regional variations using Global Burden of Disease Study data from 1990 to 2019. It also assesses the specific impact on various age groups, providing essential insights for targeted health interventions and policy-making. Methods: Data spanning from 1990 to 2019 on Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition were extracted from the 2019 Global Burden of Disease Study. Age-Standardized Incidence Rates (ASR) were computed by gender, region, and etiology, utilizing the estimated annual percentage change (EAPC) to assess temporal trends. Results: In 2019, Central Sub-Saharan Africa had the highest prevalence of Vitamin A deficiency, particularly among males, and iodine deficiency peaked in the same region for both genders. South Asia had the highest incidence of protein-energy malnutrition for both genders. Regions with a low Socio-Demographic Index (SDI) showed lower ASR for these deficiencies. Notably, Cameroon, Equatorial Guinea, and Maldives recorded the highest ASR for vitamin A deficiency, iodine deficiency, and protein-energy malnutrition, respectively. The declining ASR trend for vitamin A deficiency, especially among males, suggests effective interventions. East Asia saw a significant increase in iodine deficiency ASR from 1990 to 2019, particularly among women, requiring targeted interventions. The rising ASR of protein-energy malnutrition in several regions, especially among men, raises concerns. Vitamin A deficiency primarily affected children and adolescents, iodine deficiency predominantly impacted adolescents and young adults, and protein-energy malnutrition was chiefly observed among children under 5 years old. These findings underscore the necessity for tailored interventions considering age-specific nutritional needs and challenges.

Deciphering the genomic insights into the coexistence of congenital scoliosis and congenital anomalies of the kidney and urinary tract.

Background: Congenital scoliosis and congenital anomalies of the kidney and urinary tract are distinct genetic disorders with differing clinical manifestations. Clinically, their coexistence is not rare, but the etiologies of these complex diseases remain largely unknown, especially their shared genetic basis. Methods: We sequenced the genomes of 40 individuals diagnosed with both CS and CAKUT, alongside 2,764 controls from a Chinese Han population cohort. Our analyses encompassed gene-based and pathway-based weighted rare variant association tests, complemented by copy number variant association analyses, aiming to unravel the shared genomic etiology underlying these congenital conditions. Results: Gene-based analysis identified PTPN11 as a pivotal gene influencing both skeletal and urinary system development (P = 1.95E-21), participating in metabolic pathways, especially the MAPK/ERK pathway known to regulate skeletal and urinary system development. Pathway-based enrichment showed a significant signal in the MAPK/ERK pathway (P = 3E-04), reinforcing the potential role of PTPN11 and MAPK/ERK pathway in both conditions. Additionally, CNV analysis pinpointed IGFLR1 haploinsufficiency as a potential influential factor in the combined CS-CAKUT phenotypic spectrum. Conclusion: This study enriches our understanding of the intricate genomic interplay underlying congenital scoliosis and kidney and urinary tract anomalies, emphasizing the shared genetic foundations between these two disorders.

Global, regional, and national burden of early-onset gastric cancer.

OBJECTIVE: The burden of gastric cancer (GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017. METHODS: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates (ASIRs) were evaluated using cancer registry data from volumes X-XII of the Cancer Incidence in Five Continents (CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate (ASMR) and the Human Development Index (HDI). RESULTS: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008-2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females. CONCLUSIONS: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.

Ozone Mortality Burden Changes Driven by Population Aging and Regional Inequity in China in 2013-2050.

Air pollution exposure is closely linked to population age and socioeconomic status. Population aging and imbalance in regional economy are thus anticipated to have important implications on ozone (O3)-related health impacts. Here we provide a driver analysis for O3 mortality burden due to respiratory disease in China over 2013-2050 driven by population aging and regional inequity. Unexpectedly, we find that population aging is estimated to result in dramatic rises in annual O3 mortality burden in China; by 56, 101-137, and 298-485 thousand over the periods 2013-2020, 2020-2030, and 2030-2050, respectively. This reflects the exponential rise in baseline mortality rates with increasing age. The aging-induced mortality burden rise in 2030-2050 is surprisingly large, as it is comparable to the net national mortality burden due to O3 exposure in 2030 (359-399 thousand yr-1). The health impacts of O3 pollution, shown as mortality burden per capita, are inequitably distributed, with more severe effects in less developed provinces than their developed counterparts by 23.1% and 21.5% in 2019 and 2030, respectively. However, the regional inequity in O3 mortality burden is expected to be mitigated in 2050. This temporal variation reflects evolving demographic dividend characterized by a larger proportion of younger individuals in developed regions. These findings are critical for targeted improvement of healthcare services to ensure the sustainability of social development.