Risk factors for early TB treatment interruption among newly diagnosed patients in Malaysia

TB treatment interruption has resulted in delayed sputum conversion, drug resistance, and a high mortality rate and a prolonged treatment course, hence leading to economic and psychosocial affliction. To date, there are limited studies investigating the physico-social risk factors for early treatment interruptions. This prospective multicenter cohort study aimed to investigate the risk factors for early treatment interruption among new pulmonary tuberculosis (TB) smear-positive patients in Selangor, Malaysia. A total of 439 participants were recruited from 39 public treatment centres, 2018–2019. Multivariate Cox proportional hazard analyses were performed to analyse the risk factors for early treatment interruption. Of 439 participants, 104 (23.7%) had early treatment interruption, with 67.3% of early treatment interruption occurring in the first month of treatment. Being a current smoker and having a history of hospitalization, internalized stigma, low TB symptoms score, and waiting time spent at Directly Observed Treatment, Short-course centre were risk factors for early treatment interruption. An appropriate treatment adherence strategy is suggested to prioritize the high-risk group with high early treatment interruption. Efforts to quit smoking cessation programs and to promote stigma reduction interventions are crucial to reduce the probability of early treatment interruption.

A national survey of early treatment seeking behavior among those with incident SARS-CoV-2 infection

Background: Despite effective means to treat SARS-CoV-2 infection, the early treatment seeking behavior of those newly diagnosed with infection is not clear. Methods: We surveyed users of a national SARS-CoV-2 testing company to assess the frequency and correlates of early treatment seeking behavior for a positive test result. We recruited adults (18 years or older) who had tested positive for SARS-CoV-2 by PCR at a large clinical laboratory. To be eligible, individuals had to have a positive test result within 7 days of enrollment. Surveys were anonymous and voluntary. We collected data on demographic characteristics, general health care access and utilization, awareness of treatment for COVID-19, treatment seeking behavior, and treatments received. Descriptive statistics and odds ratios (OR) with 95% confidence intervals (95% CI) were calculated on StataSE. Results: Participants were surveyed from 3-7 January 2022: among the 15,991 who viewed a survey request, 7,647 individuals were eligible and provided responses. The median age of a respondent was 42 years (interquartile range: 32 to 54), 68.9% of respondents were women, and respondents represented 33 different states, districts, and territories. Among respondents, 23.1% reported they had sought treatment or medical advice for their current COVID-19 diagnosis. Of those who were very aware of treatment for COVID-19, 31.0% sought treatment versus 16.7% who were unaware (p-value< 0.001). The odds of treatment seeking behavior were higher for those that were contacted by a medical professional after their diagnosis (OR: 4.57 [95% CI: 3.89 to 5.37]), those with a primary doctor (OR: 2.94 [95% CI: 2.52 to 3.43]), those who self-measured their oxygen saturation (OR: 2.53 [95% CI: 2.25 to 2.84]), and those over 65 years of age (OR: 2.36 [95% CI: 2.02 to 2.76]). There was no difference in those seeking treatment based on heritage, ethnicity, prior COVID-19 diagnosis, state political affiliation, or vaccination status. The odds of seeking treatment were lower among men (OR: 0.88 [95% CI: 0.78 to 0.99]) and those without insurance (OR: 0.62 [95% CI: 0.52 to 0.72]). The most common treatment locations were clinics and most common treatments were Vitamin C, Vitamin D, Zinc, Tylenol, and NSAIDs. Conclusion: More public outreach is needed to raise awareness of the benefits of treatment for COVID-19. We found that people who were more aware about treatment for COVID-19 were more likely to seek medical advice or therapy. Efforts to increase awareness might increase early treatment for SARS-CoV-2 infection. Increased outreach with treatment facilitation from medical professionals and/or public health staff to those with newly detected SARS-CoV-2 infections, particularly among those at higher-risk of complications, might also be helpful.

Validation of Vancomycin Area under the Concentration—Time Curve Estimation by the Bayesian Approach Using One-Point Samples for Predicting Clinical Outcomes in Patients with Methicillin-Resistant Staphylococcus aureus Infections

Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections.

Early azathioprine in acute Vogt-Koyanagi-Harada disease: a prospective 24-month follow-up study with multimodal imaging and electroretinogram

Background: First-line immunosuppressive therapy (IMT) associated with high-dose corticosteroid (CS) has been proposed for the treatment of acute Vogt-Koyanagi-Harada disease (VKHD) to prevent chronicity and to prevent long-term CS side effects. However, there are very few studies that systematically evaluated visual and inflammatory outcomes in acute VKHD with early IMT. This study aimed to evaluate the outcome of high-dose corticosteroids with early addition of azathioprine (AZA) in patients with acute Vogt-Koyanagi-Harada disease (VKHD) followed for 24-month with systematic multimodal and electroretinogram exams.Methods: Prospective interventional study. Fifteen consecutive patients (30 eyes) with acute VKHD at a tertiary uveitis referral centre were followed for 24 months with systematic multimodal and full-field electroretinogram (ffERG) exams. Patients were treated with intravenous methylprednisolone followed by oral prednisone 1mg/kg/daily (CS) with slow taper and AZA introduction within 4 months. Anterior uveitis relapse, subclinical inflammation, best-corrected visual acuity (BCVA) and ffERG parameters were analyzed.Results: Fifteen patients (14 female) with a median age of 32 years were included. In the first month, 27 eyes (90%) had BCVA ≥20/40; at M24, all eyes (100%) had BCVA ≥20/25. Uveitis resolved in 28 eyes (93.3%) and became chronic recurrent in 2 eyes (6.7%); subclinical inflammation was still present in all eyes during the 24-month follow-up. ffERG parameters initially improved in all eyes; at M24, 23 eyes (76.7%) had subnormal results and 20 eyes (66.7%) had stable parameters. Eyes with very early treatment (n=12) had lower indocyanine green angiography score than eyes with early treatment (n=18) at M1 (p=0.012), but they had similar rates of recurrence, complications and ffERG parameters. Conclusion: Early AZA associated with high-dose corticosteroid was effective in improving BCVA and in controlling clinical inflammation. Isolate subclinical inflammation persisted in all eyes with no impact on ffERG in, at least, two thirds of these eyes, indicating that isolate subclinical inflammation may not be enough to indicate treatment increment.

Early Malaria diagnosis and treatment seeking Behavior among clients attending outpatient department Sekou-Toure regional referral Hospital in Mwanza, Tanzania; A Cross-Sectional Study

Background Early diagnosis of malaria and treatment seeking behavior play key role in controlling and preventing further complication related to malaria disease. Aim of this study was to determine the responses on early malaria diagnosis and treatment seeking behavior among outpatient clients attending at Sekou toure regional referral hospital in Mwanza, Tanzania. Methods A cross-sectional study was conducted among outpatient client at Sekou-Touré regional referral hospital, convenient simple random sampling used and self-administered questionnaire were used to collect data and data was entered into Microsoft excel and then exported to SPSS version 25.0 for further analysis and presented on the percentages and table. The analysis of strength of relationships between categorical variables was conducted using the Chi-square test. A p-value of ≤ 0.05 was considered to be statistically significant. Results A total of 192 respondents completed the study with a response rate of 97.6%. The study revealed that Most of the respondents about 90.6% stated they would seek treatment from health facility when symptoms appear. However, only 6.3% seek treatment within 24 hours of onset of illness (p= 0.017). Half of respondents (50.5%) experienced malaria symptoms in the past six months and only 30% seek for treatment at health facility. Preference of health facility, (51%) respondents were going direct to pharmacy to buy medicine for self-treatment. Overall, cost of service, time consumed and distance of health facility especially health center shows significant with such delay. Conclusion A low proportion of malaria-suspected patients sought treatment within 24 h of fever onset compared to the national target. Distance from the health facility, cost of service and time consumed were found to be predictors of early treatment-seeking behavior for malaria. Strengthening strategies tailored to increasing awareness for communities about malaria, importance of going hospital and early treatment-seeking behavior is essential.

Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer’s Disease Patients

Alzheimer’s disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls. The aim of the study was to identify in the late stage of AD, the key dysregulated pathways that may contribute to pathogenesis and then to evaluate whether any of these pathways could be detected in the early phase of AD, opening new opportunity for early treatment that could stop or delay the pathology. Six common pathways were found regulated by miRNAs and proteins in the late stage of AD, with one of them (Rap1 signalling) activated since the early phase. MiRNAs and proteins were also compared to explore an inverse trend of expression which could lead to the identification of new therapeutic targets. These results suggest that specific miRNA changes could represent molecular fingerprint of neurodegenerative processes and potential therapeutic targets for early intervention.