Does Prior Respiratory Viral Infection Provide Cross-Protection Against Subsequent Respiratory Viral Infections? A Systematic Review and Meta-Analysis.

The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this review was to compare the prevalence of sequential viral infections in those with previously documented positive versus negative swabs. The pooled prevalence of sequential viral infections over varying periods from 30-1000 days of follow-up was higher following a negative respiratory viral swab at 0.15 than following a positive swab at 0.08, indicating the potential protective effects of prior respiratory viral infections. However, significant heterogeneity and publication biases were noted. There is some evidence, albeit of low quality, of a possible protective effect of an initial viral infection against subsequent infections by a different virus, which is possibly due to broad, nonspecific innate immunity. Future prospective studies are needed to validate our findings.

ChatGPT as a tool to improve access to knowledge on sexually transmitted infections.

OBJECTIVES: Specific to sexual health, individuals in need of information may be adolescents who have limited ability to formally access healthcare. These digital natives may turn to ChatGPT to address their concerns on sexually transmitted infections (STI). We sought to evaluate the veracity of ChatGPT's responses to commonly asked questions on STIs. METHODS: We instructed ChatGPT (GPT 3.5) to answer STI questions from three domains, namely, (1) general risk factors for STIs, (2) access to care and diagnosis of STIs and (3) management of STIs and postexposure prophylaxis. The responses were recorded and checked against the US Centers for Disease Control and Prevention STI Treatment Guidelines 2021. RESULTS: Overall, the responses were concise and accurate. In terms of prevention, ChatGPT could also recommend measures like safe sex practices and human papillomavirus vaccination. However, it failed to recommend HIV pre-exposure prophylaxis. When an individual expressed a symptom that could potentially represent STI (eg, dyspareunia) ChatGPT appropriately provided reassurance that other possibilities exist, but advocated for testing. In terms of treatment, ChatGPT consistently communicated the importance of partner testing and follow-up testing, but at times, failed to highlight the importance of testing for other STIs. Overall, the advice given was not tailored to the specific individual's circumstances. CONCLUSIONS: ChatGPT can provide helpful information regarding STIs, but the advice lacks specificity and requires a human physician to fine-tune. Its ubiquity may make it a useful adjunct to sexual health clinics, to improve knowledge and access to care.

Infectious etiologies of persistent and chronic diarrhea in Asian developing countries: A systematic review and meta-analysis.

Infectious causes of diarrhea contribute significantly to morbidity in Asia. We conducted a systematic review and meta-analysis of the prevalence of infectious etiologies of persistent and chronic diarrhea in Asian adults. Searches were performed on PubMed and Scopus for studies from January 1, 1970, to May 30, 2023. Sixteen studies were identified and included. The meta-analysis was conducted with the random-effects method, estimating the pooled prevalence of groups of infectious pathogens as causes of persistent and chronic diarrhea among Asian adults. The findings were highly heterogeneous and indicative of publication bias. The majority of studies were conducted on persons living with human immunodeficiency virus infection (PLHIV). The studies were predominantly from low-income and middle-income Asian countries. The most common cause was parasitic, with a pooled prevalence of 0.52 (95% confidence interval 0.28-0.65, I2 = 99%, Cochran's Q = 1027.44, P < 0.01), followed by bacterial, fungal, and viral causes, which were substantially rarer. Negative microbiological testing was also common, with a pooled prevalence for a negative test being 0.37 (95% confidence interval 0.17-0.52, I2 = 99%, Cochran's Q = 1027.44, P < 0.01). Subgroup analyses of studies conducted among PLHIV, from year 2000 and among those conducted in Southeast Asia showed a similar prevalence of parasitic causes of diarrhea. In conclusion, in Asian adults with persistent and chronic diarrhea, parasitic causes were most prevalent. However, the estimate of true prevalence is limited by significant heterogeneity among the available studies. More study in this field is required, especially examining PLHIV in the post-antiretroviral therapy era and from high-income countries.

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection - Derivation of a clinical risk score.

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006-2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age> 65 years (2 points), male sex (2 points) and LDH> 770 U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60-0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41-0.66). A low-risk score of 0-1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.

Performance of Risk Scores in Predicting Infective Endocarditis in Patients with Staphylococcus aureus Bacteraemia in a Prospective Asian Cohort.

Background: Several risk scores have been derived to predict the risk of infective endocarditis (IE) amongst patients with Staphylococcus aureus bacteraemia (SAB), which helps to guide clinical management. Methods: We prospectively studied 634 patients admitted with SAB. The cohort was stratified into those with or without IE, and the PREDICT Day 1, Day 5 and VIRSTA scores were tabulated. Area under the receiver operating characteristic (AUC) curves were constructed to compare the performance of each score. Results: Of the 634 patients examined, 36 (5.7%) had IE. These patients were younger (51.6 ± 20.1 vs. 59.2 ± 18.0 years, p = 0.015), tended to have community acquisition of bacteraemia (41.7% vs. 17.9%, p < 0.001), and had persistent bacteraemia beyond 72 h (19.4% vs. 6.0%, p = 0.002). The VIRSTA score had the best performance in predicting IE (AUC 0.76, 95%CI 0.66-0.86) compared with PREDICT Day 1 and Day 5. A VIRSTA score of <3 had the best negative predictive value (97.5%), compared with PREDICT Day 1 (<4) and Day 5 (<2) (94.3% and 96.6%, respectively). Conclusions: Overall, the risk scores performed well in our Asian cohort. If applied, 23.5% of the cohort with a VIRSTA ≥ 3 would require TEE, and a score of <3 had an excellent negative predictive value.

The role of an artificial intelligence model in antiretroviral therapy counselling and advice for people living with HIV.

OBJECTIVES: People living with HIV may find personalized access to accurate information on antiretroviral therapy (ART) challenging given the stigma and costs potentially associated with attending physical consultations. Artificial intelligence (AI) chatbots such as ChatGPT may help to lower barriers to accessing information addressing concerns around ART initiation. However, the safety and accuracy of the information provided remains to be studied. METHODS: We instructed ChatGPT to answer questions that people living with HIV frequently ask about ART, covering i) knowledge of and access to ART; ii) ART initiation, side effects, and adherence, and iii) general sexual health practices while receiving ART. We checked the accuracy of the advice against international HIV clinical practice guidelines. RESULTS: ChatGPT answered all questions accurately and comprehensively. It recognized potentially life-threatening scenarios such as abacavir hypersensitivity reaction and gave appropriate advice. However, in certain contexts, such as specific geographic locations or for pregnant individuals, the advice lacked specificity to an individual's unique circumstances and may be inadequate. Nevertheless, ChatGPT consistently re-directed the individual to seek help from a healthcare professional to obtain targeted advice. CONCLUSIONS: ChatGPT may act as a useful adjunct in the process of ART counselling for people living with HIV. Improving access to information on and knowledge about ART may improve access and adherence to ART and outcomes for people living with HIV overall.

Inflammatory phenotypes may be more important than age and comorbidities in predicting clinical outcomes in hospitalised patients with COVID-19.

Objectives: In critically ill patients with COVID-19, distinct hyperinflammatory and hypoinflammatory phenotypes have been described, with different outcomes and responses to therapy. We investigated if similar phenotypes exist in non-severe illness. Methods: Consecutive patients with polymerase chain reaction (PCR) confirmed SARS-CoV-2 were examined. Baseline demographics and laboratory investigations were tabulated, including serum C-reactive protein. Patients were divided into those who were hyperinflammatory (defined as C-reactive protein >17 mg/l) or hypoinflammatory. Adverse outcomes, defined as requiring oxygenation, intensive care, or death, were recorded during the hospital stay. Clinical characteristics and outcomes were compared. Results: Of the 1781 patients examined, 276 (15.5%) had a hyperinflammatory phenotype. They were older (51.8 ± 17.2 vs 40.3 ± 13.8 years, P <0.001), had a lower PCR cycle threshold (PCR cycle threshold value 19.3 ± 6.3 vs 22.7 ± 15.4, P = 0.025) at presentation, and more medical comorbidities. The hyperinflammatory phenotype was independently associated with adverse clinical outcomes, even after adjusting for age, medical history and viral load on multivariable analyses (adjusted odds ratio 5.78, 95% confidence interval 2.86-11.63). Conclusion: Even in non-severe COVID-19, there are distinct hyper- and hypoinflammatory phenotypes, with the hyperinflammatory phenotype strongly associated with adverse clinical outcomes, that could be distinguished with a simple biomarker.

Poor sleep quality is associated with fatigue and depression in early Parkinson's disease: A longitudinal study in the PALS cohort.

Background: Sleep disorders are common in Parkinson's disease (PD). However, the longitudinal relationship between sleep quality and the other non-motor symptoms of PD has not been well characterized, especially in early PD. Objective: To explore the value of baseline sleep quality in predicting the progression of other non-motor symptoms in early PD. Methods: 109 early PD patients were recruited to the study. Patients were stratified into good and poor sleepers using the Pittsburgh Sleep Quality Index (PSQI). Assessments performed at baseline and 1 year follow-up included the Epworth Sleepiness Scale, Fatigue Severity Scale, Non-Motor Symptom Scale, Geriatric Depression Scale, Hospital Anxiety and Depression Scale, Apathy Scale, Montreal Cognitive Assessment and detailed neuropsychological assessments. Multivariable linear regression was performed at baseline to investigate differences in clinical scores between poor and good sleepers, while multivariable regression models were used to investigate associations between sleep quality and progression of test scores at 1 year follow-up. Results: 59 poor sleepers and 50 good sleepers were identified. At baseline, poor sleepers had greater HADS anxiety scores (p = 0.013) [2.99 (95% CI 2.26, 3.73)] than good sleepers [1.59 (95% CI 0.75, 2.42)]. After 1 year, poor sleepers had greater fatigue (FSS scores +3.60 as compared to -2.93 in good sleepers, p = 0.007) and depression (GDS scores +0.42 as compared to -0.70, p = 0.006). Conclusion: This study shows a longitudinal association between sleep quality, fatigue, and depression in early PD patients, independent of medication effect and disease severity, this may support the hypothesis that a common serotonergic pathway is implicated in these non-motor symptoms.

Efficacy and safety of Chinese medicine JCM-16021 for diarrhea-predominant irritable bowel syndrome: study protocol for a multi-center, randomized, double-blind, placebo controlled clinical trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disease. Adults with IBS may experience abdominal pain, change of bowel habits, and abnormal stool form without organic disease. IBS can seriously affect their work productivity and quality of life, especially diarrhea-predominant irritable bowel syndrome (IBS-D). The Chinese medicine JCM-16021 has been shown to be potentially effective in improving the symptoms of IBS-D based on a small scale clinical trial. Hence, a large scale clinical study is designed to further evaluate the efficacy and safety of the Chinese medicine JCM-16021 for IBS-D with traditional Chinese medicine (TCM) pattern of Liver Stagnation and Spleen Deficiency (LSSD). METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled clinical trial. 392 eligible participants will be enrolled with 2-week run-in, 8-week treatment and 8-week follow-up. After run-in period, participants will be randomized to receive either the Chinese medicine JCM-16021 or placebo for 8 weeks, and will have post-treatment follow up for another 8 weeks. The primary outcome is the improvement rate on the global assessment of improvement (GAI) at week 10. The secondary outcomes consist of changes of IBS-D symptoms, TCM pattern improvement, IBS-Quality of Life (IBS-QoL), IBS-Symptom Severity Score (IBS-SSS), safety, etc. RESULTS: A standard protocol has been developed for the study. The protocol will provided a detailed procedure to conduct a clinical trial and verify if the Chinese medicine JCM-16021 would significantly improve the overall symptoms of IBS-D with LSSD pattern of TCM by relieving abdominal pain, reducing stool frequency, improving the stool consistency and improving quality of life. The consolidated evidence from the study can shed light on the treatment of IBS-D with Chinese medicine. CONCLUSION: The protocol will provide details for investigators about the study following SPIRIT Statement. High-quality evidence on the efficacy and safety of Chinese medicine JCM-16021 for IBS-D will be provided through strict compliance with the protocol. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT03457324. Registered 8 February 2018, https://clinicaltrials.gov/ct2/show/NCT03457324?term=NCT03457324&draw=2&rank=1.

Subjective cognitive Complaints in early Parkinson's disease patients with normal cognition are associated with affective symptoms.

INTRODUCTION: Subjective cognitive complaints (SCC) and affective symptoms are highly prevalent in Parkinson's Disease (PD). In early PD, SCC prevalence and its affective correlates, using recommended Movement Disorders Society (MDS) Level II Criteria to define the underlying cognitive impairment, has not been previously explored. METHODS: We recruited 121 participants with early PD from two tertiary hospitals in Singapore. The presence of SCC was defined using a Non-Motor Symptoms Scale Domain-5 Score ≥1. Comprehensive neuropsychological testing was conducted with Mild Cognitive Impairment (PD-MCI) defined using recommended MDS Level II Criteria. Affective symptoms were assessed using the Hospital Anxiety Depression Scale (HADS), Geriatric Depression Scale (GDS) and Apathy Scale (AS). Analysis using multivariable linear regression model was performed. RESULTS: In our early PD cohort, SCC prevalence independent of underlying cognitive status was 38.8%. Prevalence of SCC in cognitively impaired and cognitively normal participants was 10.7% and 28.1% respectively (р = 0.241). In cognitively normal PD participants, multivariable linear regression analysis revealed that SCC was significantly associated with anxiety (ß = 0.28, 95% CI = 0.09-0.79, p = 0.014), depression (ß = 0.31, 95% CI = 0.10-0.59, p = 0.006) and apathy (ß = 0.32, 95% CI = 1.15-5.98, p = 0.004). Such an association was not found in cognitively impaired PD participants. CONCLUSION: SCC is highly prevalent even in early PD. Its implications in early PD differ depending on underlying cognitive status. SCC in cognitively impaired participants underestimates the true prevalence of PD-MCI. In contrast, SCC in cognitively normal participants is suggestive of an underlying affective disorder.

An Interglomerular Circuit Gates Glomerular Output and Implements Gain Control in the Mouse Olfactory Bulb.

Odors elicit distributed activation of glomeruli in the olfactory bulb (OB). Crosstalk between co-active glomeruli has been proposed to perform a variety of computations, facilitating efficient extraction of sensory information by the cortex. Dopaminergic/GABAergic cells in the OB, which can be identified by their expression of the dopamine transporter (DAT), provide the earliest opportunity for such crosstalk. Here we show in mice that DAT+ cells carry concentration-dependent odor signals and broadcast focal glomerular inputs throughout the OB to cause suppression of mitral/tufted (M/T) cell firing, an effect that is mediated by the external tufted (ET) cells coupled to DAT+ cells via chemical and electrical synapses. We find that DAT+ cells implement gain control and decorrelate odor representations in the M/T cell population. Our results further indicate that ET cells are gatekeepers of glomerular output and prime determinants of M/T responsiveness.