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ELife Jun 2024During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid...
During tuberculosis (TB), migration of dendritic cells (DCs) from the site of infection to the draining lymph nodes is known to be impaired, hindering the rapid development of protective T-cell-mediated immunity. However, the mechanisms involved in the delayed migration of DCs during TB are still poorly defined. Here, we found that infection of DCs with (Mtb) triggers HIF1A-mediated aerobic glycolysis in a TLR2-dependent manner, and that this metabolic profile is essential for DC migration. In particular, the lactate dehydrogenase inhibitor oxamate and the HIF1A inhibitor PX-478 abrogated Mtb-induced DC migration in vitro to the lymphoid tissue-specific chemokine CCL21, and in vivo to lymph nodes in mice. Strikingly, we found that although monocytes from TB patients are inherently biased toward glycolysis metabolism, they differentiate into poorly glycolytic and poorly migratory DCs compared with healthy subjects. Taken together, these data suggest that because of their preexisting glycolytic state, circulating monocytes from TB patients are refractory to differentiation into migratory DCs, which may explain the delayed migration of these cells during the disease and opens avenues for host-directed therapies for TB.
PubMed: 38922679
DOI: 10.7554/eLife.89319 -
Journal of Medical Microbiology Jun 2024Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have...
Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS). We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones. All admissions for HCT in a tertiary centre between January 2020 and December 2022 ( = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures. Allo-HCT was performed for 43.3 % (173/400) of patients and auto-HCT was performed for 56.7 % (227/400). A bacteraemia was documented in 28.3 % (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability ( for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.
PubMed: 38922673
DOI: 10.1099/jmm.0.001847 -
JMIR Medical Informatics Jun 2024Chronic obstructive pulmonary disease (COPD) is a chronic condition among the main causes of morbidity and mortality worldwide, representing a burden on health care...
An Ontology-Based Decision Support System for Tailored Clinical Nutrition Recommendations for Patients With Chronic Obstructive Pulmonary Disease: Development and Acceptability Study.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a chronic condition among the main causes of morbidity and mortality worldwide, representing a burden on health care systems. Scientific literature highlights that nutrition is pivotal in respiratory inflammatory processes connected to COPD, including exacerbations. Patients with COPD have an increased risk of developing nutrition-related comorbidities, such as diabetes, cardiovascular diseases, and malnutrition. Moreover, these patients often manifest sarcopenia and cachexia. Therefore, an adequate nutritional assessment and therapy are essential to help individuals with COPD in managing the progress of the disease. However, the role of nutrition in pulmonary rehabilitation (PR) programs is often underestimated due to a lack of resources and dedicated services, mostly because pneumologists may lack the specialized training for such a discipline.
OBJECTIVE
This work proposes a novel knowledge-based decision support system to support pneumologists in considering nutritional aspects in PR. The system provides clinicians with patient-tailored dietary recommendations leveraging expert knowledge.
METHODS
The expert knowledge-acquired from experts and clinical literature-was formalized in domain ontologies and rules, which were developed leveraging the support of Italian clinicians with expertise in the rehabilitation of patients with COPD. Thus, by following an agile ontology engineering methodology, the relevant formal ontologies were developed to act as a backbone for an application targeted at pneumologists. The recommendations provided by the decision support system were validated by a group of nutrition experts, whereas the acceptability of such an application in the context of PR was evaluated by pneumologists.
RESULTS
A total of 7 dieticians (mean age 46.60, SD 13.35 years) were interviewed to assess their level of agreement with the decision support system's recommendations by evaluating 5 patients' health conditions. The preliminary results indicate that the system performed more than adequately (with an overall average score of 4.23, SD 0.52 out of 5 points), providing meaningful and safe recommendations in compliance with clinical practice. With regard to the acceptability of the system by lung specialists (mean age 44.71, SD 11.94 years), the usefulness and relevance of the proposed solution were extremely positive-the scores on each of the perceived usefulness subscales of the technology acceptance model 3 were 4.86 (SD 0.38) out of 5 points, whereas the score on the intention to use subscale was 4.14 (SD 0.38) out of 5 points.
CONCLUSIONS
Although designed for the Italian clinical context, the proposed system can be adapted for any other national clinical context by modifying the domain ontologies, thus providing a multidisciplinary approach to the management of patients with COPD.
PubMed: 38922666
DOI: 10.2196/50980 -
Journal of Vector Borne Diseases Apr 2024Leishmaniasis is caused by various species of parasite Leishmania. Approximately twenty of them are pathogenic to mammals. In Sri Lanka, cutaneous leishmaniasis (CL) is...
BACKGROUND OBJECTIVES
Leishmaniasis is caused by various species of parasite Leishmania. Approximately twenty of them are pathogenic to mammals. In Sri Lanka, cutaneous leishmaniasis (CL) is an established vector-borne disease. CL originates and spreads mainly through sandfly bite in many endemic countries. The aim of the present study was to compare the geographical distribution and demographic features of CL cases in Hambantota district, Sri Lanka in 2014 and 2016.
METHODS
The patients who were presented to the Tangalle Base Hospital from June to December in 2014 and 2016 were examined and a descriptive study was carried out using a structured-questionnaire. Slit-skin smears were collected from each patient, Giemsa-stained and examined under the light microscope to identify Leishmania amastigotes.
RESULTS
Out of 256 and 314 suspected CL patients, 156 and 155 were identified positive for the year 2014 and 2016, respectively. Out of 12 District Secretary Divisions (DSD) in Hambantota district, the highest number of CL cases, 85 and 86 was reported from Tangalle DSD in 2014 and 2016 respectively. Number of identified CL patients in Beliatta DSD had increased from 50 to 67 during the study period. In both years, majority of CL patients were ≥50 years old with males more infected than females. Although CL association with occupations were insignificant, housewives were the highly (23%) infected occupants in this area.
INTERPRETATION CONCLUSION
Based on the present findings, geographical distribution within DSDs in Hambantota district had changed. This emphasizes the importance of CL as a health problem in Hambantota district.
PubMed: 38922662
DOI: 10.4103/jvbd.jvbd_117_23 -
Journal of Vector Borne Diseases Apr 2024In Port Blair, the capital of Andaman & Nicobar Islands, in the Bay of Bengal, India, there was a sudden increase in fever cases resembling the symptoms of dengue in the...
BACKGROUND OBJECTIVES
In Port Blair, the capital of Andaman & Nicobar Islands, in the Bay of Bengal, India, there was a sudden increase in fever cases resembling the symptoms of dengue in the monsoon period of 2022. Hence, an investigation was carried out to find out epidemiological and entomological reasons behind the outbreak.
METHODS
An entomological survey was carried out in 24 wards of Port Blair Municipal Council (PBMC) area, epidemiological data of last six years (January-December 2017-2021 and January-October 2022) and patient details of the year 2022 were collected. Both the epidemiological and entomological data were analyzed concerning time and place.
RESULTS
During this outbreak period tyres (22.4%) came out as a major breeding habitat followed by small discarded materials (17.5%), metal drums (15.3%), and plastic drums (11.7%). In rainy season, peri-domestic breeding (55%) was more than the domestic breeding (45%) habitat. Ae. aegypti had a high preference for indoor large containers (100-1000 L) like plastic tank, metal drum and cement tank whereasAe. albopictus prefers to breed in medium sized plastic container (20-100 L) and outdoor water receptacles like tyres, flower pots, and domestic discarded materials.
INTERPRETATION CONCLUSION
By source reduction, indoor space spray and outdoor fogging, vector density was controlled which curtailed the transmission and within eight weeks a decreasing trend of dengue cases was noticed. A regular entomological survey is crucial to know the seasonality and key breeding habitats of the vector for proper planning of vector control.
PubMed: 38922656
DOI: 10.4103/jvbd.jvbd_144_23 -
International Journal of Surgery... May 2024
PubMed: 38922645
DOI: 10.1097/JS9.0000000000001742 -
Online Journal of Public Health... Jun 2024The World Health Organization has recommended digital adherence tools (DATs) as a promising intervention to improve antituberculosis drug adherence. However, the...
BACKGROUND
The World Health Organization has recommended digital adherence tools (DATs) as a promising intervention to improve antituberculosis drug adherence. However, the acceptability of DATs in resource-limited settings is not adequately studied.
OBJECTIVE
We investigated the acceptability of a DAT among patients with tuberculosis (TB) and TB care providers in Kilimanjaro, Tanzania.
METHODS
We conducted a convergent parallel mixed methods study among patients with TB and TB care providers participating in our 2-arm cluster randomized trial (REMIND-TB). The trial aimed to investigate whether the evriMED pillbox with reminder cues and adherence feedback effectively improves adherence to anti-TB treatment among patients with TB in Kilimanjaro, Tanzania. We conducted exit and in-depth interviews among patients as well as in-depth interviews among TB care providers in the intervention arm. We conducted a descriptive analysis of the quantitative data from exit interviews. Translated transcripts and memos were organized using NVivo software. We employed inductive and deductive thematic framework analysis, guided by Sekhon's theoretical framework of acceptability.
RESULTS
Out of the 245 patients who completed treatment, 100 (40.8%) were interviewed during exit interviews, and 18 patients and 15 TB care providers were interviewed in-depth. Our findings showed that the DAT was highly accepted: 83% (83/100) expressed satisfaction, 98% (98/100) reported positive experiences with DAT use, 78% (78/100) understood how the intervention works, and 92% (92/100) successfully used the pillbox. Good perceived effectiveness was reported by 84% (84/100) of the participants who noticed improved adherence, and many preferred continuing receiving reminders through SMS text messages, indicating high levels of self-efficacy. Ethical concerns were minimal, as 85 (85%) participants did not worry about remote monitoring. However, some participants felt burdened using DATs; 9 (9%) faced difficulties keeping the device at home, 12 (12%) were not pleased with receiving daily reminder SMS text messages, and 30 (30%) reported challenges related to mobile network connectivity issues. TB care providers accepted the intervention due to its perceived impact on treatment outcomes and behavior change in adherence counseling, and they demonstrated high level of intervention coherence.
CONCLUSIONS
DATs are highly acceptable in Tanzania. However, some barriers such as TB-related stigma and mobile network connectivity issues may limit acceptance.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
RR2-10.1186/s13063-019-3483-4.
PubMed: 38922643
DOI: 10.2196/51662 -
Clinical Cancer Research : An Official... Jun 2024Development of a computational biomarker to predict, prior to treatment, the response to CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy in patients...
PURPOSE
Development of a computational biomarker to predict, prior to treatment, the response to CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy in patients with breast cancer.
EXPERIMENTAL DESIGN
A mechanistic mathematical model that accounts for protein signaling and drug mechanisms of action was developed and trained on extensive, publicly available data from breast cancer cell lines. The model was built to provide a patient-specific response score based on the expression of six genes (CCND1, CCNE1, ESR1, RB1, MYC and CDKN1A). The model was validated in five independent cohorts of 148 patients in total with early-stage or advanced breast cancer treated with endocrine therapy and CDK4/6i. Response was measured either by evaluating Ki67 levels and PAM50 risk of relapse (ROR) after neoadjuvant treatment or by evaluating progression-free survival (PFS).
RESULTS
The model showed significant association with patient´s outcomes in all five cohorts. The model predicted high Ki67 (area under the curve; AUC (95% confidence interval) of 0.80 (0.64 - 0.92), 0.81 (0.60 - 1.00) and 0.80 (0.65 - 0.93)) and high PAM50 ROR (AUC of 0.78 (0.64 - 0.89)). This observation was not obtained in patients treated with chemotherapy. In the other cohorts, patient stratification based on the model prediction was significantly associated with PFS (hazard ratio=2.92 (95% CI 1.08 - 7.86), p=0.034 and HR=2.16 (1.02 4.55), p=0.043).
CONCLUSION
A mathematical modeling approach accurately predicts patient outcome following CDK4/6i plus endocrine therapy, which marks a step towards more personalized treatments in patients with Luminal B breast cancer.
PubMed: 38922642
DOI: 10.1158/1078-0432.CCR-24-0244 -
Journal of Addiction Medicine Jun 2024Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed...
BACKGROUND
Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders.
OBJECTIVE
Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic.
METHODS
The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other secondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry.
RESULTS
Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) and methamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8-43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%).
CONCLUSIONS
Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes.
PubMed: 38922639
DOI: 10.1097/ADM.0000000000001334 -
Expert Review of Anti-infective Therapy Jun 2024Non-typhoidal (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation... (Review)
Review
INTRODUCTION
Non-typhoidal (NTS) bacteremia is common in sub-Saharan Africa. We examined the prevalence of antibiotic resistance to fluoroquinolones, third-generation cephalosporins, and multi-drug resistance (MDR) in NTS human isolates from sub-Saharan Africa.
METHODS
A systematic review was conducted using a search in Ovid Medline, Embase, and African Index Medicus of publications between 2000 and 2021. A random-effects model meta-analysis was performed using data from 66 studies that included 29,039 NTS blood and 1,065 stool isolates.
RESULTS
The pooled prevalence proportions of MDR were 0.685 (95% CI 0.574-0.778) and 0.214 (0.020-0.785) in blood vs. stool isolates. The corresponding estimates of fluoroquinolones resistance were 0.014 (0.008-0.025) vs. 0.021 (0.012-0.036) and third-generation cephalosporins resistance 0.019 (0.012-0.031) vs. 0.035 (0.006-0.185). Similar results were found for children and adults. Resistance prevalence to these antibiotics in blood isolates increased between 2000-2010 and 2011-2021. The guidelines employed to determine antimicrobial resistance and epidemiological characteristics (e.g. sample size, study duration) correlated with the resistance prevalence.
CONCLUSIONS
The prevalence of MDR and resistance to fluoroquinolones and third-generation cephalosporins in NTS in sub-Saharan Africa is alarming.
EXPERT OPINION
Standardized surveillance of antimicrobial drug resistance in NTS in sub-Saharan Africa is warranted to guide healthcare policymaking and antibiotic stewardship programs.
PubMed: 38922636
DOI: 10.1080/14787210.2024.2368989