Obstructive Sleep Apnea and Medical Comorbidities in the Asian Population: Evidence From a Nationwide Healthcare System Data in South Korea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a breathing disorder characterized by recurrent airway obstruction during sleep. Previous western studies have investigated the link between medical disorders and the pathophysiology of OSA. The prevalence and comorbidity rates of OSA; however, vary across different countries and racial groups. This study aimed to delve into medical comorbidities in patients with OSA using a large nationwide healthcare database in Korea. METHODS: This nationwide study used the Korean National Health Insurance claims database (2010-2019). The effect of OSA on the incidence of medical disorders was estimated using the Cox proportional hazard ratio (HR) model. The results were reported as crude and adjusted HRs with 95% confidence intervals (CI). Subgroup analysis was conducted by sex and age. RESULTS: In total, 103,785 patients with OSA and 207,570 patients without OSA were included. OSA group had significantly higher HRs for ischemic heart disease and stroke even after adjusting for hypertension, dyslipidemia, and diabetes. The OSA group also showed an increased risk of metabolic syndrome-related diseases, chronic kidney disease, and gastroesophageal reflux disease. Female patients with OSA exhibited notably higher rates of comorbid liver cirrhosis, chronic obstructive pulmonary disease, and asthma. The cardiovascular burden of patients increased in accordance with the patients' age. CONCLUSION: Korean patients with OSA have a significantly increased risk of cardio-cerebrovascular diseases, which aligns with the previous studies conducted in the western countries. This result holds particular significance as it represents the first nationwide, population-based study conducted in Asia.

Advances in Alphavirus and Flavivirus Research.

Newly emerging viruses, primarily zoonotic or vector-borne, pose a persistent threat to public health and have led to outbreaks of global concern [...].

Association Between Hypnotics and Dementia: A Mini Narrative Review.

OBJECTIVE: This narrative review aims to provide a comprehensive assessment of the existing literature on the relationship between hypnotics and dementia, considering both potential link and inconclusive or lack of association. METHODS: Data from studies that investigate the association between hypnotic medications and dementia were reviewed. Studies included both cohort studies and systematic reviews, participants with various type of dementia and hypnotics including benzodiazepines (BZDs) and Z-drugs (ZDs). RESULTS: The existing literatures presents conflicting evidence regarding the association between hypnotics, including BZDs and ZDs, and the risk of dementia. Some studies suggest a potential link between prolonged use of hypnotics and an increased risk of dementia. However, other studies indicate inconclusive or lacking evidence regarding this association. Factors such as study design, sample characteristics, and control of confounding variables contribute to the variability in findings. CONCLUSION: The relationship between hypnotics and dementia remains complex and controversial. While some studies suggest a potential association, others find inconclusive or conflicting evidence. Future research should focus on addressing methodological limitations, considering classifying dementia subtypes, and try to adjust medication lag time.

Bipolar Disorder, Circadian Rhythm and Clock Genes.

Sleep disturbance and abnormal circadian rhythm might be closely related to bipolar disorder. Several studies involving disturbed sleep/wake cycle, changes in rhythms such as melatonin and cortisol, clock genes, and circadian preference have shown the relationship between bipolar disorder and circadian rhythm. The results differed across different studies. In some studies, a delay in the circadian rhythm was observed in the depressive episode and advanced circadian rhythm was observed during the manic episode. In other studies, a delay in circadian rhythm was observed independent of mood episodes. Accordingly, circadian rhythm disorder was proposed as a trait marker for bipolar disorder. The altered circadian rhythm may represent a pathological mechanism that contributes to the mood episodes. However, a prospective cohort study is needed for further clarification.

The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial.

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.

Immune responses to typhoid conjugate vaccine in a two dose schedule among Nepalese children <2 years of age.

BACKGROUND: Previously, the Vi-typhoid conjugate vaccine (Vi-TT) was found to be highly efficacious in Nepalese children under 16 years of age. We assessed the immunogenicity of Vi-TT at 9 and 12 months of age and response to a booster dose at 15 months of age. METHODS: Infants were recruited at Patan Hospital, Kathmandu and received an initial dose of Vi-TT at 9 or 12 months of age with a booster dose at 15 months of age. Blood was taken at four timepoints, and antibody titres were measured using a commercial ELISA kit. The primary study outcome was seroconversion (4-fold rise in antibody titre) of IgG one month after both the doses. FINDINGS: Fifty children were recruited to each study group.Some visits were disrupted by the COVID19 pandemic and occurred out of protocol windows.Both the study groups attained 100 % IgG seroconversion after the initial dose. IgG seroconversion in the 9-month group was significantly higher than in the 12-month group (68.42 % vs 25.8 %, p < 0.001). Among individuals who attended visits per protocol, IgG seroconversion after the first dose occurred in 100 % of individuals (n = 27/27 in 9-month and n = 32/32 in 12-month group). However, seroconversion rates after the second dose were 80 % in the 9-month and 0 % in the shorter dose-interval 12-month group (p < 0.001) (n = 16/20 and n = 0/8, respectively). INTERPRETATION: Vi-TT is highly immunogenic at both 9 and 12 months of age. Stronger response to a booster in the 9-month group is likely due to the longer interval between doses.

Characterization of Codeine Treatment Responders Among Patients with Refractory or Unexplained Chronic Cough: A Prospective Real-World Cohort Study.

PURPOSE: Codeine is a narcotic antitussive often considered for managing patients with refractory or unexplained chronic cough. This study aimed to evaluate the proportion and characteristics of patients who responded to codeine treatment in real-world practice. METHODS: Data from the Korean Chronic Cough Registry, a multicenter prospective cohort study, were analyzed. Physicians assessed the response to codeine based on the timing and degree of improvement after treatment initiation. Follow-up assessments included the Leicester Cough Questionnaire and cough severity visual analog scale at six months. In a subset of subjects, objective cough frequency was evaluated following the initiation of codeine treatment. RESULTS: Of 305 patients, 124 (40.7%) responded to treatments based on anatomic diagnostic protocols, while 181 (59.3%) remained unexplained or refractory to etiological treatments. Fifty-one subjects (16.7%) were classified as codeine treatment responders (those showing a rapid and clear response), 57 (18.7%) as partial responders, and 62 (20.3%) as non-responders. Codeine responders showed rapid improvement in objective cough frequency and severity scores within a week of the treatment. At 6 months, responders showed significantly improved scores in cough scores, compared to non-responders. Several baseline parameters were associated with a more favorable treatment response, including older age, non-productive cough, and the absence of heartburn. CONCLUSIONS: Approximately 60% of chronic cough patients in specialist clinics may require antitussive drugs. While codeine benefits some, only a limited proportion (about 20%) of patients may experience rapid and significant improvement. This underscores the urgent need for new antitussive drugs to address these unmet clinical needs.

Association between weekend catch-up sleep and the risk of prediabetes and diabetes: A cross-sectional study using KNHANES.

BACKGROUND: The objectives of this cross-sectional study were to explore the relationship between weekend catch-up sleep (WCUS) and the risk of prediabetes/diabetes and to assess how this risk varies based on WCUS duration, using a large population sample in South Korea. METHODS: Data were sourced from the 2021 Korea National Health and Nutrition Examination Survey, involving 2472 subjects aged 30 years and above, employed, and not using blood glucose-lowering medications. Prediabetes/diabetes risk was examined based on the presence of WCUS. Participants were categorized into four groups by WCUS duration (< 1, ≥ 1 and < 2, ≥ 2 and < 3, and ≥ 3 h) to evaluate the prediabetes/diabetes risk across varying WCUS durations. RESULTS: No significant difference in prediabetes/diabetes risk was observed between the WCUS and non-WCUS groups. In subgroup analysis, a WCUS duration of 1 to 2 h was related to a lower odds ratio of prediabetes (aOR = 0.618, 95% CI = 0.382-0.999), while 3 h or more was associated with a higher odds ratio of diabetes (aOR = 3.098, 95% CI = 1.561-6.149). CONCLUSIONS: In individuals who experience insufficient sleep during weekdays and manage to achieve the optimal average sleep duration of 1 to 2 h of WCUS, WCUS was associated with improved blood glucose regulation. However, compensating for excessive weekday sleep deprivation with WCUS of 3 h or more was associated with impaired blood glucose regulation.

Human papillomavirus detection rates in Bowen disease: correlation with pelvic and digital region involvement and specific p53 immunostaining patterns.

BACKGROUND: The relationship between human papillomavirus (HPV) and Bowen disease (BD) is not fully understood. OBJECTIVES: To investigate the differences in HPV detection rates in BD samples across various body regions and analyse the expression patterns of p53, p16 and Ki-67 in relation to HPV presence. METHODS: Tissue samples from patients diagnosed with BD, confirmed through histopathology, were retrospectively collected. Next-generation sequencing was used for HPV DNA detection. Immunohistochemistry (IHC) for p16, p53 and Ki-67 was performed. RESULTS: Out of 109 patients with BD, 21 (19.3%) were HPV-positive. All identified types were α-HPVs, with HPV-16 being the most common. The HPV detection rate was significantly higher in the pelvic (9/13, 69%, P < 0.001) and digital (5/10, 50%, P = 0.02) areas compared with those in the other regions. HPV presence was significantly correlated with p53 negativity (P = 0.002), the p53 'non-overexpression' IHC pattern (P < 0.001) and p16-p53 immunostain pattern discordance (P < 0.001). Conversely, there was no notable association between HPV presence and p16 positivity, the p16 IHC pattern or Ki-67 expression. CONCLUSIONS: Our findings suggest the oncogenic role of sexually transmitted and genito-digitally transmitted α-HPVs in the pathogenesis of BD in pelvic and digital regions.

Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.