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BMC Infectious Diseases, 24.06.2024
Tilføjet 24.06.2024
Abstract Background Currently, several studies have observed that chronic hepatitis B virus infection is associated with the pathogenesis of kidney disease. However, the extent of the correlation between hepatitis B virus infection and the chronic kidney disease risk remains controversial. Methods In the present study, we searched all eligible literature in seven databases in English and Chinese. The random effects model was used to conduct a meta-analysis. Quality of included studies was assessed using the Newcastle-Ottawa Quality Scale. Results In this analysis, a total of 31 studies reporting the association between hepatitis B virus infection and chronic kidney disease risk were included. The results showed a significant positive association between hepatitis B virus infection and the risk of chronic kidney disease (pooled OR, 1.20; 95% CI, 1.12–1.29), which means that hepatitis B virus increases the risk of developing chronic kidney disease. Conclusion This study found that hepatitis B virus infection was associated with a significantly increased risk of chronic kidney disease. However, the current study still cannot directly determine this causal relationship. Thus, more comprehensive prospective longitudinal studies are needed in the future to provide further exploration and explanation of the association between hepatitis B virus and the risk of developing chronic kidney disease.
Læs mere Tjek på PubMedRoyce-Nagel, Galen; Jarzebowski, Mary; Wongsripuemtet, Pattrapun; Krishnamoorthy, Vijay; Fuller, Matthew; Ohnuma, Tetsu; Treggiari, Miriam; Yaport, Miguel; Cobert, Julien; Garrigan, Ethan; Bartz, Raquel; Raghunathan, Karthik
Critical Care Explorations, 24.06.2024
Tilføjet 24.06.2024
OBJECTIVES: To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. PATIENTS: Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. INTERVENTION: The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. MEASUREMENTS: Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. MAIN RESULTS: Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06–1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08–1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12–1.27]). There were no associations for hospital LOS (17 [10–27] vs. 17 [9–28], MR: 1.05 [0.99–1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95–1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92–1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05–1.19]). CONCLUSIONS: In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.
Læs mere Tjek på PubMedFernando, Shannon M.; Tran, Alexandre; Soliman, Karim; Flynn, Barbara; Oommen, Thomas; Wenzhe, Li; Adhikari, Neill K.J.; Kanji, Salmaan; Seely, Andrew J.E.; Fox-Robichaud, Alison E.; Wax, Randy S.; Cook, Deborah J.; Lamontagne, François; Rochwerg, Bram
Critical Care Explorations, 24.06.2024
Tilføjet 24.06.2024
OBJECTIVES: Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock. DATA SOURCES: We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024. STUDY SELECTION: We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration. DATA EXTRACTION: Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. DATA SYNTHESIS: We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47–0.94], low certainty) and hospital length of stay (mean difference [MD] –2.1 d [95% CI, –1.4 to –2.8], low certainty). MB may also reduce duration of vasopressors (MD –31.1 hr [95% CI, –16.5 to –45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1–14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, –0.2% to 2.0%], very low certainty). We did not find any differences in adverse events. CONCLUSIONS: Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed. REGISTRATION: Center for Open Science (https://osf.io/hpy4j).
Læs mere Tjek på PubMedForget, Marie-France; Wang, Han Ting; Carignan, Raphaelle; Dessureault, Alexandre; Gravel, Mathieu; Bienvenue, Jeanne; Bouchard, Maude; Durivage, Camille; Coveney, Richard; Munshi, Laveena
Critical Care Explorations, 24.06.2024
Tilføjet 24.06.2024
OBJECTIVES: Older adults may be under-represented in critical care research, and results may not apply to this specific population. Our primary objective was to evaluate the prevalence of inclusion of older adults across critical care trials focused on common ICU conditions or interventions. Our secondary objective was to evaluate whether older age was used as a stratification variable for randomization or outcome analysis. DESIGN, SETTING AND SUBJECTS: We performed a systematic review of previously published systematic reviews of randomized controlled trials (RCTs) in critical care. We searched PubMed, Ovid, CENTRAL, and Cochrane from 2009 to 2022. Systematic reviews of any interventions across five topics: acute respiratory distress syndrome (ARDS), sepsis/shock, nutrition, sedation, and mobilization were eligible. MAIN RESULTS: We identified 216 systematic reviews and included a total of 253 RCTs and 113,090 patients. We extracted baseline characteristics and the reported proportion of older adults. We assessed whether any upper age limit was an exclusion criterion for trials, whether age was used for stratification during randomization or data analysis, and if age-specific subgroup analysis was present. The most prevalent topic was sepsis (78 trials, 31%), followed by nutrition (62 trials, 25%), ARDS (39 trials, 15%), mobilization (38 trials, 15%), and sedation (36 trials, 14%). Eighteen trials (7%) had exclusion criteria based on older age. Age distribution with information on older adults prevalence was given in six trials (2%). Age was considered in the analysis of ten trials (5%) using analytic methods to evaluate the outcome stratified by age. Conclusions: In this systematic review, the proportion of older critically ill patients is undetermined, and it is unclear how age is or is not an effect modifier or to what extent the results are valid for older adult groups. Reporting age is important to guide clinicians in personalizing care. These results highlight the importance of incorporating older critically ill patients in future trials to ensure the results are generalizable to this growing population.
Læs mere Tjek på PubMedMichael, Henry Ukachukwu; Brouillette, Marie-Josée; Tamblyn, Robyn; Fellows, Lesley K.; Mayo, Nancy E.
AIDS, 24.06.2024
Tilføjet 24.06.2024
Objective: This study aims to estimate the extent to which anticholinergic and sedative burden is associated with cognitive ability and self-reported cognitive difficulties (SCD) in middle-aged and older adults living with HIV. Design: This cross-sectional analysis examined data from the inaugural visit of participants enrolled in the Positive Brain Health Now (BHN) study. Methods: Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM; higher is better) and SCD using the Perceived Deficits Questionnaire (PDQ; higher is worse). Medication burden was quantified using several scoring systems, including the Anticholinergic Cognitive Burden (ACB), Anticholinergic and Sedative Burden Catalog (ACSBC), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and the Sedative Load Model (SLM). Multivariable Ordinary Least Squares and quantile regression were utilized to estimate average effects and distribution-specific impacts, respectively. Results: Of 824 participants (mean age 53 years, 84.7% men), 41.4% used anticholinergics (ACSBC) and 39% used sedatives (SLM). High anticholinergic burden was linked to worse cognitive ability (β = -3.81; 95% CI: -7.16, -0.46) and SCD (β = 3.89; 95% CI: 1.08, 6.71). Using three or more anticholinergics worsened cognitive ability (β = -4.45; 95% CI: -8.54, -0.35), and using three or more sedatives increased SCD (β = 4.35; 95% CI: 0.92 -7.78). Stronger negative associations were observed in participants with lower cognitive ability and more difficulties. Conclusions: These results suggest that anticholinergic and sedative burden may contribute to cognitive impairment in people with HIV. Personalized medication management and regular cognitive assessments could mitigate these adverse effects. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRose, Penelope C.; Davies, Claire; Cotton, Mark F.; Otwombe, Kennedy; Browne, Sara H.; Vaida, Florin; Innes, Steve; Nel, Etienne De la Rey
AIDS, 24.06.2024
Tilføjet 24.06.2024
Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging cause of liver disease in HIV. Transient elastography (TE) with controlled attenuation parameter (CAP) measures liver stiffness as a marker of liver fibrosis and CAP as a measure of hepatic steatosis. Our aim was to evaluate longitudinal CAP and liver stiffness in children with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) from early life compared to HIV-uninfected children (HU). Design: Prospective cohort study Methods: PHIV and HU were followed annually for two years. During the study, 60% of PHIV switched from older ART regimens to tenofovir disoproxil, lamivudine and dolutegravir (TLD). Longitudinal evolution of CAP and liver stiffness were investigated in two PHIV groups - on older ART and on TLD - compared to HU children using linear mixed effects models. Results: 263 children and adolescents (112 PHIV, 151 HU) aged 7-20 years were followed. PHIV on older ART had CAP 8.61% (95% CI 4.42% to 12.97%, p
Læs mere Tjek på PubMedMartinson, Tyler; Montoya, Rikki; Moreira, Carlos; Kuncze, Karen; Sassaman, Kevin; Heise, Megan J.; Glidden, David V.; Amico, K. Rivet; Arnold, Emily A.; Buchbinder, Susan P.; Ewart, Leah Davis; Carrico, Adam; Wang, Guohong; Okochi, Hideaki; Scott, Hyman M.; Gandhi, Monica; Spinelli, Matthew A.
AIDS, 24.06.2024
Tilføjet 24.06.2024
Background: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower PrEP adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS). Methods: YMSM/TGW participants (n = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/mL) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days. Results: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (< 4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation (AOR 6.1; 95% CI: 1.4–11; p = 0.005) and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value. Conclusions: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedKing, Jonathan M.; Dobbins, Timothy; Keen, Phillip; Cornelisse, Vincent J.; Stoové, Mark; Nigro, Steven J.; Asselin, Jason; Higgins, Nasra; Mao, Limin; Aung, Htein Linn; Petoumenos, Kathy; McGregor, Skye
AIDS, 24.06.2024
Tilføjet 24.06.2024
Objective: To identify groups more likely to be referred for HIV testing because of symptomatic presentation rather than as part of asymptomatic screening. Design: A retrospective analysis of Australian National HIV Registry (NHR) surveillance data including sociodemographic and clinical data, as well as reasons for HIV test. Methods: Using notification records from 2017 to 2022, we summarised reasons for testing leading to an HIV diagnosis. Reasons for testing were combined with clinical status at diagnosis to derive HIV testing categories: testing while symptomatic; asymptomatic HIV screening; seroconversion; and other test reason. We stratified these categories by stage of HIV at diagnosis with late-stage HIV defined as a CD4 count
Læs mere Tjek på PubMedSchnittman, Samuel R.; Talathi, Ria; Wilks, Moses Q.; Hedgire, Sandeep; Lu, Michael T.; Fourman, Lindsay T.; Alagpulinsa, David A.; Stockman, Sara L.; White, Kevin S.; Wallis, Zoey K.; Autissier, Patrick; Stanley, Takara L.; Lee, Hang; Honigberg, Michael C.; El-Fakhri, Georges; Williams, Kenneth C.; Zanni, Markella V.; Grinspoon, Steven K.; Toribio, Mabel
AIDS, 24.06.2024
Tilføjet 24.06.2024
People with human immunodeficiency virus (HIV, PWH) face an increased risk of cardiovascular disease (CVD) compared to the general population. We previously demonstrated that people with (versus without) HIV have higher macrophage-specific arterial infiltration in relation to systemic monocyte activation. We now show that select T lymphocyte subpopulations (naïve CD4+, effector memory CD4+, and central memory CD8+) are differentially associated with macrophage-specific arterial infiltration among participants with versus without HIV, with evidence of interaction by HIV status. Our results suggest that among PWH, circulating T lymphocytes associate with macrophage-specific arterial infiltration, of relevance to atherogenesis and CVD risk. Clinical Trials Registration: NCT02542371 Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedRusso, Samuel C.; Ockene, Mollie W.; Arpante, Allison K.; Johnson, Julia E.; Lee, Hang; Toribio, Mabel; Stanley, Takara L.; Hadigan, Colleen M.; Grinspoon, Steven K.; Erlandson, Kristine M.; Fourman, Lindsay T.
AIDS, 24.06.2024
Tilføjet 24.06.2024
Objective: Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. Design: We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily versus identical placebo among participants on INSTI-based regimens at baseline. Methods: In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms. Results: Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm2, P = 0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P = 0.03). Tesamorelin was well-tolerated with a similar frequency of adverse events including hyperglycemia between groups. Conclusions: The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedYotebieng, Marcel; Zotova, Natalia; Bernard, Charlotte; Goodrich, Suzanne; Awoh, Ajeh Rogers; Watnick, Dana; Nsonde, Dominique Mahambu; Moungang, Elodie Flore Tchiengang; Noumedem, Julie Laure Nguemo; Mbongo’o, Guy Calvin Nko’o; Minga, Albert; Seydi, Moussa; Gandou, Paul; Kwobah, Edith Kamaru; Atwoli, Lukoye; Jaquet, Antoine; Wools-Kaloustian, Kara; Anastos, Kathryn; the IeDEA Consortium
AIDS, 24.06.2024
Tilføjet 24.06.2024
Objective: The aim of this study was to assess the performance of the 9-item Patient Health questionnaire (PHQ-9) against psychiatrist diagnosis in PLWH. Design: Cross-sectional analysis of data collected between January 2018 and July 2022 across five sites in Cameroon, Cote d’Ivoire, Kenya, Senegal, and the Republic of Congo. Participants were ≥18 years and receiving HIV care at the participating site. PHQ-9 was administered by study staff followed by a psychiatrist\'s evaluation within 3 days. Results: Overall, 778 participants with complete data were included: 297 (38.2%) in Cameroon, 132 (17.0%) in Congo, 148 (19.0%) in Cote d’Ivoire, 98 (12.6%) in Kenya, and 103 (13.2%) in Senegal. The area under the curve for PHQ-9 score was generally high ranging from 0.935 (95% CI: 0.893, 0.977) in Cote d’Ivoire to 0.768 (95% CI: 0.589, 0.947) in Congo. However, for the common cut-off score ≥10, sensitivity was low: 50% or lower in Cameroon, Congo and Senegal, 66.7% in Kenya and 70.6% in Cote d’Ivoire. But negative predictive values (NPV) were high: 98.9% (95% CI: 96.9%, 99.8%) in Cameroon, 96.1 (95% CI: 91.1, 98.7) in Cote d’Ivoire, 96.3% (95% CI: 89.7%, 99.2%) in Kenya, 95.7% (95% CI: 90.2%, 98.6%) in Congo, and 89.0% (95% CI: 81.2%, 94.4%) in Senegal. Interpretation: Across all countries, PHQ-9 score ≥10 performed very poorly (low sensitivity) as a tool to identify psychiatrist diagnosed depression. However, the observed high NPV suggests it can be used to rule out depression. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedBlair, Jessica; Kempf, Mirjam-Colette; Dionne, Jodie A.; Causey-Pruitt, Zenoria; Wise, Jenni M.; Jackson, Elizabeth A.; Muntner, Paul; Hanna, David B.; Kizer, Jorge R.; Fischl, Margaret A.; Ofotokun, Igho; Ramirez, Catalina; Gange, Stephen J.; Brill, Ilene K.; Levitan, Emily B.
AIDS, 24.06.2024
Tilføjet 24.06.2024
Objectives: Timely control of hypertension is vital to prevent comorbidities. We evaluated the association of race/ethnicity and HIV infection with incident hypertension outcomes, including awareness, treatment, and control. Design: We evaluated cisgender women living with HIV and sociodemographically matched women living without HIV recruited into four Southern sites of the Women\'s Interagency HIV Study (2013-2019). Methods: We calculated measurements of the time to four events or censoring: incident hypertension, hypertension awareness, hypertension treatment, and hypertension control. Hazard ratios for race/ethnicity and HIV status were calculated for each outcome using Cox proportional-hazards models adjusted for sociodemographic, behavioral, and clinical risk factors. Results: Among 712 women, 56% were hypertensive at baseline. Forty-five percent of the remaining women who were normotensive at baseline developed incident hypertension during follow-up. Non-Hispanic White and Hispanic women had faster time to hypertension control compared to non-Hispanic Black women (p = 0.01). In fully adjusted models, women living with HIV who were normotensive at baseline had faster time to treatment compared to normotensive women living without HIV (p = 0.04). Conclusions: In our study of women in the US South, non-Hispanic Black women became aware of their hypertension diagnosis more quickly than non-Hispanic White and Hispanic women but were slower to control their hypertension. Additionally, women living with HIV more quickly treated and controlled their hypertension compared to women living without HIV. JOURNAL/aids/04.03/00002030-990000000-00511/figure1/v/2024-06-19T100448Z/r/image-jpeg Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Læs mere Tjek på PubMedFEMS Microbiology Reviews, 24.06.2024
Tilføjet 24.06.2024
Abstract The co-selective pressure of heavy metals is a contributor to the dissemination and persistence of antibiotic resistance genes in environmental reservoirs. The overlapping range of antibiotic and metal contamination and similarities in their resistance mechanisms point to an intertwined evolutionary history. Metal resistance genes are known to be genetically linked to antibiotic resistance genes, with plasmids, transposons, and integrons involved in the assembly and horizontal transfer of the resistance elements. Models of co-selection between metals and antibiotic have been proposed, however the molecular aspects of these phenomena are in many cases not defined or quantified and the importance of specific metals, environments, bacterial taxa, mobile genetic elements, and other abiotic or biotic conditions are not clear. Co-resistance is often suggested as a dominant mechanism, but interpretations are beset with correlational bias. Proof of principle examples of cross-resistance and co-regulation have been described but more in-depth characterisations are needed, using methodologies that confirm functional expression of resistance genes and that connect genes with specific bacterial hosts. Here, we comprehensively evaluate the recent evidence for different models of co-selection from pure culture and metagenomic studies in environmental contexts and we highlight outstanding questions.
Læs mere Tjek på PubMedMalaria Journal, 23.06.2024
Tilføjet 23.06.2024
Abstract Background Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria. Methods Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients’ general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented. Results 532 imported malaria cases were diagnosed over 11 years (2013–2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26–60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died. Conclusions The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.06.2024
Tilføjet 23.06.2024
Abstract Background Despite emerging evidence linking blood cell indices (BCIs) to sepsis mortality, the inconsistency of observational studies obscures the clarity of these associations. This study aims to clarify the causal influence of BCIs on 28-day mortality rates in sepsis patients. Methods Utilizing univariable and multivariable Mendelian randomization (MR) analyses, we examined the impact of BCIs on sepsis mortality by analyzing data from extensive genome-wide association studies. The inverse-variance weighted (IVW) method was our primary analytic tool, complemented by several robustness checks to mitigate pleiotropy, including weighted median, mode-based estimates, MR-Egger regression, and MR-PRESSO. Subsequently, we conducted a retrospective study to further explore the correlation between platelet indices and 28-day mortality of sepsis using real-world data. Results Our findings highlight a significant causal relationship between platelet distribution width (PDW) and 28-day mortality in sepsis, with the univariable Mendelian randomization approach yielding an odds ratio of 1.12 (95% CI, 1.06–1.26; P
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.06.2024
Tilføjet 23.06.2024
Abstract Background Spinal tuberculosis (STB) is a local manifestation of systemic infection caused by Mycobacterium tuberculosis, accounting for a significant proportion of joint tuberculosis cases. This study aimed to explore the diagnostic value of MRI combined with mannose-binding lectin (MBL) for STB. Methods 124 patients suspected of having STB were collected and divided into STB and non-STB groups according to their pathological diagnosis. Serum MBL levels were measured using ELISA and a Pearson analysis was constructed to determine the correlation between MBL and STB. ROC was plotted to analyze their diagnostic value for STB. All the subjects included in the study underwent an MRI. Results The sensitivity of MRI for the diagnosis of STB was 84.38% and specificity was 86.67%. The serum MBL levels of the patients in the STB group were significantly lower than the levels in the non-STB group. ROC analysis results indicated that serum MBL’s area under the curve (AUC) for diagnosis of STB was 0.836, with a sensitivity of 82.3% and a specificity was 77.4%. The sensitivity of MRI combined with MBL diagnosis was 96.61%, and the specificity was 92.31%, indicating that combining the two diagnostic methods was more effective than using either one alone. Conclusions Both MRI and MBL had certain diagnostic values for STB, but their combined use resulted in a diagnostic accuracy than either one alone.
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.06.2024
Tilføjet 23.06.2024
Abstract Background Although administrative claims data have a high degree of completeness, not all medically attended Respiratory Syncytial Virus-associated lower respiratory tract infections (RSV-LRTIs) are tested or coded for their causative agent. We sought to determine the attribution of RSV to LRTI in claims data via modeling of temporal changes in LRTI rates against surveillance data. Methods We estimated the weekly incidence of LRTI (inpatient, outpatient, and total) for children 0–4 years using 2011–2019 commercial insurance claims, stratified by HHS region, matched to the corresponding weekly NREVSS RSV and influenza positivity data for each region, and modelled against RSV, influenza positivity rates, and harmonic functions of time assuming negative binomial distribution. LRTI events attributable to RSV were estimated as predicted events from the full model minus predicted events with RSV positivity rate set to 0. Results Approximately 42% of predicted RSV cases were coded in claims data. Across all regions, the percentage of LRTI attributable to RSV were 15–43%, 10–31%, and 10–31% of inpatient, outpatient, and combined settings, respectively. However, when compared to coded inpatient RSV-LRTI, 9 of 10 regions had improbable corrected inpatient LRTI estimates (predicted RSV/coded RSV ratio
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.06.2024
Tilføjet 23.06.2024
Abstract Background Toll-Like receptors (TLRs) play an important role in the immune response during hepatitis B virus (HBV) infection. In this study, we evaluated the association between two SNP variants (TLR3 rs3775290 and TLR4 rs4986790) and susceptibility to chronic HBV infection in Mauritania. Subjects and methods : A total of 188 subjects were recruited for this study: 102 chronically infected patients and 86 individuals with spontaneously resolved HBV infection who were considered controls. Targeted PCR products were sequenced using Sanger sequencing. Results We found that TLR3 rs3775290 was significantly more frequent in patients with chronic HBV than in the control population (p = 0.03). However, no association was found between the TLR4 rs3775290 polymorphism and chronic infection. Conclusion Our results suggest that the TLR3 rs3775290 polymorphism may be a risk factor for susceptibility to chronic HBV infection in the Mauritanian population.
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.06.2024
Tilføjet 23.06.2024
Abstract Objective To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT). Methods This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages. Results Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month. Conclusion Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.
Læs mere Tjek på PubMedKatie R. Hughes, Andrew P. Waters
Trends in Parasitology, 23.06.2024
Tilføjet 23.06.2024
Small-Saunders et al. uncovered a new facet of artemisinin resistance in Plasmodium in which parasites use a previously underexplored arm of stress response mechanisms. Through altered epitranscriptomic modifications on tRNA, changed translation patterns adapt resistant cells to facilitate entry into a quiescent-like state which provides the parasite an escape from many drugs.
Læs mere Tjek på PubMedGretchen Diffendall, Artur Scherf
Trends in Parasitology, 23.06.2024
Tilføjet 23.06.2024
The protozoan parasite Plasmodium falciparum, responsible for the deadliest form of human malaria, employs antigenic variation via monoallelic expression as a key survival strategy. The selective activation of one out of the 60-member var gene family is key to understanding the parasite\'s ability to cause severe disease and evade the host immune response. var gene activation is initiated by its relocation to a specialized expression site. While the perinuclear expression site (PES) plays a crucial role in enabling the expression of a single allele, the characteristics of this PES remain largely obscure. Recent breakthroughs in genome editing tools and the discovery of regulatory noncoding RNAs have shed light on this intriguing biological feature, offering significant insights into the mechanisms of pathogen virulence.
Læs mere Tjek på PubMedInfectious Disease Modelling, 23.06.2024
Tilføjet 23.06.2024
Publication date: Available online 21 June 2024 Source: Infectious Disease Modelling Author(s): Zihan Hao, Shujuan Hu, Jianping Huang, Jiaxuan Hu, Zhen Zhang, Han Li, Wei Yan
Læs mere Tjek på PubMedInfection, 22.06.2024
Tilføjet 22.06.2024
Abstract Introduction The COVID-19 pandemic has underscored the importance of its potential long-term health effects, including its link to new-onset asthma in children. Asthma significantly impacts children’s health, causing adverse outcomes and increased absenteeism. Emerging evidence suggests a potential association between COVID-19 infection and higher rates of new-onset asthma in adults, raising concerns about its impact on children’s respiratory health. Methods A retrospective cohort study design was employed, using electronic medical records from the TriNetX database, covering January 1, 2021, to December 31, 2022. Two cohorts of children aged 5 to 18 who underwent SARS-CoV-2 RT-PCR testing were analyzed: unvaccinated children with and without COVID-19 infection, and vaccinated children with and without infection. Propensity score matching was used to mitigate selection bias, and hazard ratio (HR) and 95% CI were calculated to assess the risk of new-onset asthma. Results Our study found a significantly higher incidence of new-onset asthma in COVID-19 infected children compared to uninfected children, regardless of vaccination status. In Cohort 1, 4.7% of COVID-19 infected children without vaccination developed new-onset asthma, versus 2.0% in their non-COVID-19 counterparts within a year (HR = 2.26; 95% CI = 2.158–2.367). For Cohort 2, COVID-19 infected children with vaccination showed an 8.3% incidence of new-onset asthma, higher than the 3.1% in those not infected (HR = 2.745; 95% CI = 2.521–2.99). Subgroup analyses further identified higher risks in males, children aged 5–12 years, and Black or African American children. Sensitivity analyses confirmed the reliability of these findings. Conclusion The study highlights a strong link between COVID-19 infection and an increased risk of new-onset asthma in children, which is even more marked in those vaccinated. This emphasizes the critical need for ongoing monitoring and customized healthcare strategies to mitigate the long-term respiratory impacts of COVID-19 in children, advocating for thorough strategies to manage and prevent asthma amidst the pandemic.
Læs mere Tjek på PubMedInfection, 22.06.2024
Tilføjet 22.06.2024
Abstract Purpose C-reactive protein (CRP), as an acute phase protein, is a sensitive indicator of neonatal bacterial infection. Some recent studies have shown that there is a correlation between CRP levels in serum and saliva, and using saliva to detect CRP levels is expected to be an ideal and non-invasive method to predict neonatal infection. The purpose of this Meta-analysis was to evaluate the diagnostic value of salivary CRP for neonatal infection. Methods We searched PubMed, Embase, Web of Science, and Scopus databases in October 2023 and included observational studies that examined salivary CRP in newborns with bacterial infections. Data was extracted regarding the methodology, participant characteristics, and outcome measures. Results Nine articles were included, with a total of 696 newborns. Salivary CRP levels are significantly higher in neonates with infections compared to non-infected group (SMD = 0.58, 95%CI [0.40–0.76], P
Læs mere Tjek på PubMedPradeep Annamalai SubramaniPhornpimon TiptharaSurendra Kumar KolliJustin NicholasSamantha J. BarnesMadison M. OgbondahKevin C. KobylinskiJoel TarningJohn H. Adams1Center for Global Health and Interdisciplinary Research, College of Public Health, University of South Florida, Tampa, Florida, USA2Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand3Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA4Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand5Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United KingdomAudrey Odom John
Antimicrobial Agents And Chemotherapy, 22.06.2024
Tilføjet 22.06.2024
Mads Lindholm KurtzhalsAnders NormanErik SvenssonTroels LillebaekDorte Bek Folkvardsen1International Reference Laboratory of Mycobacteriology, Statens Serum Institut, Copenhagen, Denmark2Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkJared A. Silverman
Antimicrobial Agents And Chemotherapy, 22.06.2024
Tilføjet 22.06.2024
Young Rong Kim, Hakjun Hyun, Eun Jin Kim, Young Hwa Choi, Jin Sae Yoo, Yeunji Lee, Hong Sang Oh, Jung Yeon Heo
International Journal of Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
The human nasopharynx is the only reservoir for meningococcal colonization and the major source of transmission between humans, resulting in invasive diseases. Most meningococcal carriage isolates are not pathogenic. However, under certain circumstances, a minority of carried meningococci, regarded as hyperinvasive strains, can invade the bloodstream and cause Invasive meningococcal disease (IMD) [1]. Although the association between the carriage state and invasive disease is not fully elucidated, meningococcal carriage studies can improve our understanding of the epidemiology and pathogenesis of meningococcal disease and evaluate the effect of meningococcal vaccines on the carriage state, eventually measuring the effectiveness of meningococcal vaccines against carriage as a prerequisite for IMD development [2].
Læs mere Tjek på PubMedMichael Hoelscher, David Barros-Aguirre, Masoud Dara, Norbert Heinrich, Eugene Sun, Christoph Lange, Simon Tiberi, Charles Wells
Clinical Microbiology and Infection, 22.06.2024
Tilføjet 22.06.2024
Tuberculosis (TB) is the leading cause of mortality by an infectious disease world-wide. Despite national and international efforts, the world is not on track to end TB by 2030. Antibiotic treatment of TB is longer than for most infectious diseases and complicated by frequent adverse events. To counter emerging Mycobacterium tuberculosis drug resistance and provide effective, safe drug treatments of shorter duration, novel anti-TB medicines and treatment regimens are needed. Through a joint global effort, more candidate medicines are in the clinical phases of drug development than ever before.
Læs mere Tjek på PubMedJennifer Cohn, Manica Balasegaram, Hema Srinivasan, Leena Menghaney, Mirfin Mpundu, Brenda Waning, Yewande Alimi, Jennifer Cohn, Manica Balasegaram, Hema Srinivasan, L.L.B. Leena Menghaney, Mirfin Mpundu, Brenda Waning, Yewande Alimi
Clinical Microbiology and Infection, 22.06.2024
Tilføjet 22.06.2024
Antibiotics are indispensable to modern healthcare, yet their equitable access remains a pressing global challenge. Factors contributing to inequities include insufficient evidence for optimal clinical use, limited registration, pricing for Reserve antibiotics, and supply chain challenges. These issues disproportionately affect low- and middle-income countries (LMICs), exacerbating antimicrobial resistance (AMR) burdens.
Læs mere Tjek på PubMedLiselotte Hardy, Tine Vermoesen, Birgitta Gleeson, Cecilia Ferreyra, Peter Dailey, Jan Jacobs
Clinical Microbiology and Infection, 22.06.2024
Tilføjet 22.06.2024
Blood culture bottles (BCBs) are designed for high-income countries without considering the humidity and heat in low- and middle-income countries (LMIC). A published target product profile for use of BCBs in LMIC (1) identified the need for storage stability testing at 5-40°C and 90% humidity, contrasting with the 20 – 25°C currently reported by manufacturers. The target product profile also calls for a 12-months shelf life, but this doesn’t allow for the lengthy process of international shipping, custom clearance, and in-country distribution.
Læs mere Tjek på PubMedWujian Ke, Cailing Ao, Liuyuan Wang, Xiaohui Zhang, Jingwei Shui, Jianhui Zhao, Liping Huang, Xingying Leng, Rui Zhu, Haiying Wang, Wenjia Weng, Lianhong Zheng, Ligang Yang, Shixing Tang
Clinical Microbiology and Infection, 22.06.2024
Tilføjet 22.06.2024
Invasive lumbar puncture (LP) is the conventional method for diagnosing neurosyphilis (NS). We investigated a noninvasive alternative method to detect serum Treponema pallidum specific antibodies against highly immunogenic antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) by using luciferase immunosorbent assay (LISA).
Læs mere Tjek på PubMedMilbourn, H., McCartney, D., Richmond, A., Campbell, A., Flaig, R., Robertson, S., Fawns-Ritchie, C., Hayward, C., Marioni, R. E., McIntosh, A. M., Porteous, D. J., Whalley, H. C., Sudlow, C.
BMJ Open, 22.06.2024
Tilføjet 22.06.2024
PurposeGeneration Scotland (GS) is a large family-based cohort study established as a longitudinal resource for research into the genetic, lifestyle and environmental determinants of physical and mental health. It comprises extensive genetic, sociodemographic and clinical data from volunteers in Scotland. ParticipantsA total of 24 084 adult participants, including 5501 families, were recruited between 2006 and 2011. Within the cohort, 59% (approximately 14 209) are women, with an average age at recruitment of 49 years. Participants completed a health questionnaire and attended an in-person clinic visit, where detailed baseline data were collected on lifestyle information, cognitive function, personality traits and mental and physical health. Genotype array data are available for 20 026 (83%) participants, and blood-based DNA methylation (DNAm) data for 18 869 (78%) participants. Linkage to routine National Health Service datasets has been possible for 93% (n=22 402) of the cohort, creating a longitudinal resource that includes primary care, hospital attendance, prescription and mortality records. Multimodal brain imaging is available in 1069 individuals. Findings to dateGS has been widely used by researchers across the world to study the genetic and environmental basis of common complex diseases. Over 350 peer-reviewed papers have been published using GS data, contributing to research areas such as ageing, cancer, cardiovascular disease and mental health. Recontact studies have built on the GS cohort to collect additional prospective data to study chronic pain, major depressive disorder and COVID-19. Future plansTo create a larger, richer, longitudinal resource, ‘Next Generation Scotland’ launched in May 2022 to expand the existing cohort by a target of 20 000 additional volunteers, now including anyone aged 12+ years. New participants complete online consent and questionnaires and provide postal saliva samples, from which genotype and salivary DNAm array data will be generated. The latest cohort information and how to access data can be found on the GS website (www.generationscotland.org).
Læs mere Tjek på PubMedMurayama, A., Kugo, H., Senoo, Y.
BMJ Open, 22.06.2024
Tilføjet 22.06.2024
ObjectiveClinical practice guidelines (CPGs) are essential for standardising patient care based on evidence-based medicine. However, the presence of financial conflicts of interest (COIs) among CPG authors can undermine their credibility. This study aimed to examine the extent and size of COIs among authors of psychiatry CPGs in Japan. MethodsThis cross-sectional analysis of disclosed payments from pharmaceutical companies assesses the prevalence and magnitude of personal payments for lecturing, consulting and writing to CPGs for bipolar disorder and major depressive disorder in Japan between 2016 and 2020. ResultsThis study found that 93.3% of authors received payments over a 5-year period, with total payments exceeding US$4 million. The median payment per author was US$51 403 (IQR: US$9982–US$111 567), with a notable concentration of payments among a small number of authors, including the CPG chairperson. Despite these extensive financial relationships, only a fraction of authors disclosed their COIs in the CPGs. These large amounts of personal payments were made by pharmaceutical companies manufacturing new antidepressants and sleeping aids listed in the CPGs. ConclusionsThis study found that more than 93% of authors of CPGs for major depressive disorder and bipolar disorder in Japan received considerable amounts of personal payments from the pharmaceutical industry. The findings highlight deviations from international COI management standards and suggest a need for more stringent COI policies for psychiatry CPGs in Japan.
Læs mere Tjek på PubMedSevelius, J., Veras, M. A. S. M., Gomez, J. L., Saggese, G., Mocello, A. R., Bassichetto, K. C., Neilands, T. B., Lippman, S. A.
BMJ Open, 22.06.2024
Tilføjet 22.06.2024
IntroductionGlobally, transgender (‘trans’) women experience extreme social and economic marginalisation due to intersectional stigma, defined as the confluence of stigma that results from the intersection of social identities and positions among those who are oppressed multiple times. Among trans women, gender-based stigma intersects with social positions such as engagement in sex work and substance use, as well as race-based stigma to generate a social context of vulnerability and increased risk of HIV acquisition. In Brazil, trans women are the ‘most at-risk’ group for HIV, with 55 times higher estimated odds of HIV infection than the general population; further, uptake of HIV testing and pre-exposure prophylaxis (PrEP) among trans women is significantly lower than other at-risk groups. Through extensive formative work, we developed Manas por Manas, a multilevel intervention using HIV prevention strategies with demonstrated feasibility and acceptability by trans women in Brazil, to address intersectional stigma and increase engagement in the HIV prevention continuum. Methods and analysisWe are conducting a two-arm randomised wait-list controlled trial of the intervention’s efficacy in São Paulo, Brazil, to improve uptake of HIV testing and PrEP among transgender women (N=400). The primary outcomes are changes in HIV testing (self-testing and clinic based), changes in PrEP uptake and changes in PrEP persistence at baseline and follow-up assessment for 12 months at 3-month intervals. Ethics and disseminationThis study was approved by University of California, San Francisco Institutional Review Board (15-17910) and Comissão Nacional de Ética em Pesquisa (Research Ethics National Commission, CAAE: 25215219.8.0000.5479) in Brazil. Participants provided informed consent before enrolment. We are committed to collaboration with National Institutes of Health officials, other researchers, and health and social services communities for rapid dissemination of data and sharing of materials. The results will be published in peer-reviewed academic journals and scientific presentations. Trial registration number NCT03081559.
Læs mere Tjek på PubMedSpinnewijn, L., Aarts, J. W., Braat, D., Scheele, F.
BMJ Open, 22.06.2024
Tilføjet 22.06.2024
ObjectivesThis study uses the diffusion of innovations (DOI) theory to comprehensively understand the adoption of shared decision-making (SDM) in clinical practice, specifically focusing on the ‘knowledge’ and ‘persuasion’ stages within DOI. We aim to understand the challenges and dynamics associated with SDM adoption, offering insights for more patient-centred decision-making in healthcare. DesignThis qualitative study employs a modified framework analysis approach, integrating ethnographic and interview data from prior research, along with additional interviews. The framework used is based on the DOI theory. Study setting and participantsThis study was conducted in the obstetrics and gynaecology department of a tertiary teaching hospital in the Eastern region of the Netherlands. It included interviews with 20 participants, including gynaecologists, obstetrics registrars and junior doctors currently practising in the department. Additionally, data from prior research conducted within the same department were incorporated, ensuring the maintenance of contextual consistency. ResultsFindings reveal a complex interplay between SDM’s benefits and challenges. Clinicians value SDM for upholding patient autonomy and enhancing medical practice, viewing it as valuable for medical decision-making. Decision aids are seen as advantageous in supporting treatment decisions. Challenges include compatibility issues between patient and clinician preferences, perceptions of SDM as time-consuming and difficult and limitations imposed by the rapid pace of healthcare and its swift decisions. Additionally, perceived complexity varies by situation, influenced by colleagues’ attitudes, with limited trialability and sparsely observed instances of SDM. ConclusionsClinicians’ decision to adopt or reject SDM is multifaceted, shaped by beliefs, cognitive processes and contextual challenges. Cognitive dissonance is critical as clinicians reconcile their existing practices with the adoption of SDM. Practical strategies such as practice assessments, open discussions about SDM’s utility and reflective practice through professional development initiatives empower clinicians to make the best informed decision to adopt or reject SDM.
Læs mere Tjek på PubMedKoychev, I., Adler, A. I., Edison, P., Tom, B., Milton, J. E., Butchart, J., Hampshire, A., Marshall, C., Coulthard, E., Zetterberg, H., Hellyer, P., Cormack, F., Underwood, B. R., Mummery, C. J., Holman, R. R.
BMJ Open, 22.06.2024
Tilføjet 22.06.2024
IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1 RAs), currently marketed for type 2 diabetes and obesity, may offer novel mechanisms to delay or prevent neurotoxicity associated with Alzheimer’s disease (AD). The impact of semaglutide in amyloid positivity (ISAP) trial is investigating whether the GLP-1 RA semaglutide reduces accumulation in the brain of cortical tau protein and neuroinflammation in individuals with preclinical/prodromal AD. Methods and analysisISAP is an investigator-led, randomised, double-blind, superiority trial of oral semaglutide compared with placebo. Up to 88 individuals aged ≥55 years with brain amyloid positivity as assessed by positron emission tomography (PET) or cerebrospinal fluid, and no or mild cognitive impairment, will be randomised. People with the low-affinity binding variant of the rs6971 allele of the Translocator Protein 18 kDa (TSPO) gene, which can interfere with interpreting TSPO PET scans (a measure of neuroinflammation), will be excluded. At baseline, participants undergo tau, TSPO PET and MRI scanning, and provide data on physical activity and cognition. Eligible individuals are randomised in a 1:1 ratio to once-daily oral semaglutide or placebo, starting at 3 mg and up-titrating to 14 mg over 8 weeks. They will attend safety visits and provide blood samples to measure AD biomarkers at weeks 4, 8, 26 and 39. All cognitive assessments are repeated at week 26. The last study visit will be at week 52, when all baseline measurements will be repeated. The primary end point is the 1-year change in tau PET signal. Ethics and disseminationThe study was approved by the West Midlands—Edgbaston Research Ethics Committee (22/WM/0013). The results of the study will be disseminated through scientific presentations and peer-reviewed publications. Trial registration number ISRCTN71283871.
Læs mere Tjek på PubMedOyato, B. T., Debele, T., Edosa, D., Abasimel, H. Z., Awol, M., Kebede, E. T., Gezahagn, A., Desta, A. A., Alemu, F. T., Asfaw, S. B.
BMJ Open, 22.06.2024
Tilføjet 22.06.2024
ObjectiveTo identify determinants of puerperal sepsis among postpartum women attending East Shoa Zone public hospitals, Central Ethiopia, 2023. Design and settingAn institutional-based, unmatched case–control study was conducted from 19 June 2023 to 4 September 2023, in East Shoa Zone public hospitals. Participants495 postpartum women (100 cases and 395 controls) were selected using systematic sampling techniques. Data were collected through face-to-face interviews and from medical charts using a pretested, structured questionnaire. The AOR with its corresponding 95% CI was used to identify determinant variables. Findings were presented in texts and tables. Outcome measuresThe medical charts of participants were reviewed to identify those who had developed puerperal sepsis. ResultsAnaemia (AOR 6.05; 95% CI 2.57 to 14.26), undernourishment (AOR 4.43; 95% CI 1.96 to 10.01), gestational diabetes mellitus (AOR 3.26; 95% CI 1.22 to 8.74), postpartum haemorrhage (AOR 3.17; 95% CI 1.28 to 7.87), obstructed labour (AOR 2.76; 95% CI 1.17 to 6.52), multiparity (AOR 2.54; 95% CI 1.17 to 5.50), placenta previa (AOR 2.27; 95% CI 1.11 to 4.67) and vaginal examination ≥5 times (AOR 2.19; 95% CI 1.05 to 4.54) were the independent determinants of puerperal sepsis in this study. ConclusionThis study found that gestational diabetes mellitus, anaemia, undernourishment, placenta previa, obstructed labour, postpartum haemorrhage and five or more per-vaginal examinations during labour were the determinants of puerperal sepsis. Therefore, it is recommended that obstetric care providers strictly adhere to guidelines on the number of vaginal exams that should be performed throughout labour and that they perform these exams using the appropriate infection-prevention techniques. In addition, they should provide comprehensive health education on nutrition during pregnancy and postnatal periods and the importance of iron supplements.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. Case presentation We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient’s condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. Conclusions To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Oncogenic types of human Papillomavirus (HPV) infection cause substantial morbidity and mortality in Nigeria. Nigeria has low cervical cancer screening and vaccination rates, suggesting the need for community engagement to enhance reach and uptake. We organised a designathon to identify community-led, innovative approaches to promote HPV screening and vaccination for women and girls, respectively, in Nigeria. A designathon is a three-phase participatory process informed by design thinking that includes the preparation phase that includes soliciting innovative ideas from end-users, an intensive collaborative event to co-create intervention components, and follow-up activities. Methods We organised a three-phase designathon for women (30-65yrs) and girls (11-26yrs) in Nigeria. First, we launched a national crowdsourcing open call for ideas on community-driven strategies to support HPV screening among women and vaccination among girls. The open call was promoted widely on social media and at in-person gatherings. All eligible entries were graded by judges and 16 exceptional teams (with 4-6members each). All six geo-political zones of Nigeria were invited to join an in-person event held over three days in Lagos to refine their ideas and present them to a panel of expert judges. The ideas from teams were reviewed and scored based on relevance, feasibility, innovation, potential impact, and mother-daughter team dynamics. We present quantitative data on people who submitted and themes from the textual submissions. Results We received a total of 612 submissions to the open call from mother-daughter dyads. Participants submitted ideas via a website designated for the contest (n = 392), in-person (n = 99), email (n = 31), or via an instant messaging application (n = 92). Overall, 470 were eligible for judging after initial screening. The average age of participants for daughters was 19 years and 39 years for mothers. Themes from the top 16 proposals included leveraging local leaders (5/16), faith-based networks (4/16), educational systems (4/16), and other community networks (7/16) to promote awareness of cervical cancer prevention services. After an in-person collaborative event, eight teams were selected to join an innovation training boot camp, for capacity building to implement ideas. Conclusions Innovative strategies are needed to promote HPV screening for mothers and vaccination for girls in Nigeria. Our designathon was able to facilitate Nigerian mother-daughter teams to develop cervical cancer prevention strategies. Implementation research is needed to assess the effectiveness of these strategies.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Globally, there were an estimated 39 million people living with HIV with 1.3 million new HIV infections by the end of 2023. The Sub-Saharan Africa accounted 51% of new HIV infections. HIV case-based Surveillance collects data on newly diagnosed HIV cases, recent HIV infections, and other sentinel events, aiding evidence-based decision making. There is limited evidence on these in Ethiopia. The objective of this study is to determine the incidence proportion of recent infections and associated factors among newly diagnosed HIV cases and their distribution by person, place, and time in the Southwest Ethiopia Regional State. Methods A retrospective analysis was conducted on HIV case-based surveillance dataset (July 2019 to June 2022) from the Southwest Ethiopia Regional State. Recent HIV infection is an infection that acquired within the last 12 months as diagnosed by Asante recency test kits. Data were analyzed using SPSS version 26. ArcGIS version 10.8 was used for mapping recent infections. Logistic regression was employed to identify factors associated with recent infections. In multivariable logistic regression analysis, variables with p-value
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP. Methods Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM). Results 97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97–0.99; p
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 – 24 years seeking medical services at a major public hospital in Sierra Leone. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests. Results Of the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20—24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex—Female (OR, 0.51; 95% CI, 0.28–0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 – 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00–1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08–0.84; p = 0.024), Overweight—Body mass index (OR, 0.10; 95% CI, 0.01–0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01–0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%). Conclusion We reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Introduction Since the mpox outbreak in 2022, it was unclear if and how often infections with mpox virus (MPXV) were clinically inapparent, i.e. not presenting to clinical care with mpox symptoms. Moreover, it was hypothesized that MPXV circulated in the affected communities before the outbreak was officially detected. Methods We retrospectively tested rectal and urethral swabs, and pooled samples for presence of MPXV. Samples were obtained from routine STI testing of three anonymous Community Based Voluntary Counselling and Testing (CBVCT) centres in Berlin, in 2022 and 2023. Testing results were linked to anonymously provided behavioural data. Results Overall, 9,053 samples from 6,600 client visits were included. Clinically inapparent MPXV infections were detectable in 1.1% of the samples. We did not find MPXV infections in the month before the first cases appeared in Berlin or between October 2022 and January 2023 when case numbers were low in Germany. However, during the outbreak period in 2022, we found clinically inapparent MPXV infections among 2.2% of the clients and during summer/autumn 2023 among 0.3%. The number of condomless anal/vaginal intercourse partners within the previous 6 months and PrEP use were identified as predictors of clinically inapparent MPXV infection. Conclusion Clinically inapparent MPXV infections occurred during the mpox outbreak in Berlin in 2022 and post-outbreak in summer/autumn 2023. Unrecognized MPXV circulation in Berlin before the recognition of the outbreak in May 2022 appears unlikely. However, low-level sustained circulation of clinically inapparent MPXV infections need to be acknowledged in mpox prevention strategies.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Planned behaviors and self-care against the coronavirus are two important factor in controlling its spread and self-care behaviors depend on the level of health literacy. This research was conducted to determine the mediating role of health literacy in the relationship between elements of planned behavior and self-care in dealing with the Covid-19. Methods In this descriptive-analytical quantitative study, the sample size was calculated using Cochrane’s formula and considering a p-value of 0.51, α = 0.05, and d = 0.05, and 313 students were selected based on stratified and random method. To gather data and assess various aspects of variables, a questionnaires were utilized, focusing on health literacy, self-car and planned behavior. The relationship between the variables was examined by SPSS version 26 and via descriptive statistics, including the mean and standard deviation, and inferential statistics such as Pearson’s correlation coefficient (P = 0.05), path analysis, and determining the standard coefficients between self-care and planned behavior, mediated by the indicators of the health literacy. Results A significant difference was found between the level of health literacy of women and men. The comparison of the mean health literacy and self-care behavior in terms of other variables did not show any significant difference. Meanwhile, the comparison of health status control behaviors, hand washing, and mask use did not show any significant difference between the two groups. A positive and significant correlation was found between self-care behaviors, attitude, subjective norms, perceived behavioral control, and behavioral intention. The relationship of health literacy and psychological variables of attitude, subjective norms, and perceived behavioral control with self-care against COVID-19 was significant. Conclusion The direct and significant impact of health literacy on individuals’ self-care behaviors against the coronavirus was not observed. However, health literacy did have a significant effect on subjective norms. This finding is important because subjective norms significantly influenced individuals’ behavioral intention, which in turn had a significant effect on self-care behaviors against the coronavirus. Thus, health literacy played a mediating role in this relationship. Furthermore, attitude emerged as the strongest predictor of behavioral intention, exerting a direct effect. Conversely, perceived behavioral control did not directly and significantly affect students’ self-care behaviors.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Blood-based transcriptional gene signatures for tuberculosis (TB) have been developed with potential use to diagnose disease. However, an unresolved issue is whether gene set enrichment analysis of the signature transcripts alone is sufficient for prediction and differentiation or whether it is necessary to use the original model created when the signature was derived. Intra-method comparison is complicated by the unavailability of original training data and missing details about the original trained model. To facilitate the utilization of these signatures in TB research, comparisons between gene set scoring methods cross-data validation of original model implementations are needed. Methods We compared the performance of 19 TB gene signatures across 24 transcriptomic datasets using both rrebuilt original models and gene set scoring methods. Existing gene set scoring methods, including ssGSEA, GSVA, PLAGE, Singscore, and Zscore, were used as alternative approaches to obtain the profile scores. The area under the ROC curve (AUC) value was computed to measure performance. Correlation analysis and Wilcoxon paired tests were used to compare the performance of enrichment methods with the original models. Results For many signatures, the predictions from gene set scoring methods were highly correlated and statistically equivalent to the results given by the original models. In some cases, PLAGE outperformed the original models when considering signatures’ weighted mean AUC values and the AUC results within individual studies. Conclusion Gene set enrichment scoring of existing gene sets can distinguish patients with active TB disease from other clinical conditions with equivalent or improved accuracy compared to the original methods and models. These data justify using gene set scoring methods of published TB gene signatures for predicting TB risk and treatment outcomes, especially when original models are difficult to apply or implement.
Læs mere Tjek på PubMedBMC Infectious Diseases, 22.06.2024
Tilføjet 22.06.2024
Abstract Background Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19. Methods For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology. Findings CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033). Interpretation Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles.
Læs mere Tjek på PubMedNakjun Choi Eunna Choi Yong-Joon Cho Min Jung Kim Hae Woong Choi Eun-Jin Lee a Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, South Koreab Department of Molecular Bioscience, Multidimensional Genomics Research Center, College of Biomedical Science, Kangwon National University, Chuncheon, South Korea
Virulence, 22.06.2024
Tilføjet 22.06.2024
Matthieu Domenech de Cellès, Pejman Rohani
Nat Rev Microbiol, 22.06.2024
Tilføjet 22.06.2024
Emanuela Buschi, Antonio Dell’Anno, Michael Tangherlini, Marco Candela, Simone Rampelli, Silvia Turroni, Giorgia Palladino, Erika Esposito, Marco Lo Martire, Luigi Musco, Sergio Stefanni, Cristina Munari, Jessica Fiori, Roberto Danovaro, Cinzia Corinaldesi
Science Advances, 22.06.2024
Tilføjet 22.06.2024