by Nisha Jha, Bibechan Thapa, Samyam Bickram Pathak, Sajala Kafle, Anish Mudvari, Pathiyil Ravi Shankar Introduction The access, watch, and reserve (AWaRe) classification of antibiotics was developed in 2019 by the WHO Expert Committee on the Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national, and global levels. The objectives of this study were to assess the availability of antibiotics as per WHO AWaRe classification at community pharmacies located around a tertiary care hospital in Lalitpur and to compare these antibiotics with the national essential medicine list of Nepal. Method The cross-sectional study was conducted at community pharmacies located within a two-kilometer radius of a teaching hospital from August to November 2022. A total of 82 community pharmacies registered with the Nepal Chemist and Druggists Association and the Department of Drug Administration were studied. Data was collected using a standard proforma containing the names of the antibiotics classified as per the WHO’s AWaRe classification. Results Access group of antibiotics, Ampicillin, (82;100%), Amoxycillin, (82;100%), Flucloxacillin, (82;100%), and Metronidazole, (82;100%) were available in all community pharmacies. Results from the watch group showed that Azithromycin, (80; 97.6%) was available in all pharmacies followed by Cefixime, (80; 97.6%), Ciprofloxacin, (73; 89%), Levofloxacin, (74; 90.2%)and Ofloxacin, (74; 90.2%). Linezolid, (24; 29.3%) was the most common antibiotics available from the reserve group of antibiotics. Colistin was the second commonly available antibiotic. The most available antibiotic from the not recommended group were Ampicillin/Cloxacillin (82; 100%), followed by Piperacillin/Sulbactam, (39; 47.6%). There were differences in the classification of antibiotics between the WHO AWaRe list and the Essential Medicines list of Nepal in terms of numbers of antibiotics listed. Conclusion Antibiotics from the not recommended and reserve groups were commonly available in community pharmacies. The implementation of antibiotic guidelines should be emphasized along with strict monitoring of the sale of antibiotics without a prescription in community pharmacy settings. …

by Xiaofeng Wu, Song Yang, Di Zhang, Liang Zhang Deep foundation pit settlement prediction based on machine learning is widely used for ensuring the safety of construction, but previous studies are limited to not fully considering the spatial correlation between monitoring points. This paper proposes a transformer-based deep learning method that considers both the spatial and temporal correlations among excavation monitoring points. The proposed method creates a dataset that collects all excavation monitoring points into a vector to consider all spatial correlations among monitoring points. The deep learning method is based on the transformer, which can handle the temporal correlations and spatial correlations. To verify the model’s accuracy, it was compared with an LSTM network and an RNN-LSTM hybrid model that only considers temporal correlations without considering spatial correlations, and quantitatively compared with previous research results. Experimental results show that the proposed method can predict excavation deformations more accurately. The main conclusions are that the spatial correlation and the transformer-based method are significant factors in excavation deformation prediction, leading to more accurate prediction results.

by Shafaq Fatima, Ayesha Afzal, Hamna Rashid, Saba Iqbal, Rosheen Zafar, Komal Khalid, Ayman Rauf, Maryam Majeed, Aqsa Malik, Chris G. Carter This experiment aimed to investigate the effects of partial substitution of crude protein from soybean meal (SBM) with black soldier fly (Hermetia illucens) larvae meal (BSFLM) in juvenile rohu (Labeo rohita) and catla (Catla catla). Four isonitrogenous diets (23% crude protein) were formulated to replace 0% (T0), 40% (T40), 80% (T80) and 100% (T100) crude protein from SBM with BSFLM. Triplicate groups of each species (10 fish per replicate) were fed in an eight week growth experiment. After final sampling (n = 20 fish per dietary group), the remaining fish were exposed to bacterial (Staphylococcus aureus) challenge (0.80 CFU/ml) for 15 days. Rohu fed with BSFLM substituted diets showed significantly higher growth and feed conversion ratio as compared to those in T0. Catla fed with BSFLM substituted diets showed slightly higher growth indices. The growth response of rohu to BSFLM substitution was better than that noted in catla in all groups. The chemical composition, amino acids and fatty acids profile, haematological and biochemical parameters, levels of liver function enzymes measured in T0, T40, T80 and T100 were similar between four dietary groups in both species. However, the maximum value of cholesterol and triglycerides were noted in T100 both in catla and rohu. The values of lauric acid, α-linolenic acid, decosahexanoic acid, n3:n6 fatty acids ratio progressively increased with dietary increase of BSFLM in both species. At end of the growth experiment, the levels of catalase, superoxide dismutase and lysozyme increased linearly with the inclusion of BSFLM in both species while malondialdehyde showed similar values between different groups. However, catalase, and superoxide dismutase increased (T0…

by Yihua Wang, Richard J. Travers, Alanna Farrell, Qing Lu, Jennifer L. Bays, Alec Stepanian, Christopher Chen, Iris Z. Jaffe BCR-ABL tyrosine kinase inhibitors (TKIs) have dramatically improved survival in Philadelphia chromosome-positive leukemias. Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib. Recent studies implicate endothelial cell (EC) damage in this toxicity by unknown mechanisms with few side-by-side comparisons of multiple TKIs and with no available data on endothelial impact of recently approved TKIs or novels TKIs being tested in clinical trials. To characterize BCR-ABL TKI induced EC dysfunction we exposed primary human umbilical vein ECs in 2D and 3D culture to clinically relevant concentrations of seven BCR-ABL TKIs and quantified their impact on EC scratch-wound healing, viability, inflammation, and permeability mechanisms. Dasatinib, ponatinib, and nilotinib, the TKIs associated with thrombosis in patients, all significantly impaired EC wound healing, survival, and proliferation compared to imatinib, but only dasatinib and ponatinib impaired cell migration and only nilotinib enhanced EC necrosis. Dasatinib and ponatinib increased leukocyte adhesion to ECs with upregulation of adhesion molecule expression in ECs (ICAM1, VCAM1, and P-selectin) and leukocytes (PSGL1). Dasatinib increased permeability and impaired cell junctional integrity in human engineered microvessels, consistent with its unique association with pleural effusions. Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

by Yanxi Liu, Xuan Cheng, Dengzhao Tang, Xinyue Wang Civil aviation transport is an important source of global respiratory disease spread due to the closely-spaced environment. In order to reduce the probability of infection of passengers, an improved Wells-Riley model for cabin passenger risk assessment have been given in this work, the cabin ventilation and passenger nose and mouth orientation were considered. The model’s effectiveness has been verified with published data. Finally, how the load factor and use of an empty seat scheme are associated with the number of infected people was assessed. The results demonstrated that the number of infected people positively correlates with the passenger load factor, and the most suitable load factor can be determined by controlling the final number of infected people with the condition of the epidemic situation in the departure city. Additionally, infection risk was found to be lower among passengers in window seats than in those in aisle seats and middle seats, and keeping empty seats in the middle or aisle could reduce the cabin average probability of infection by up to 37.47%. Using the model developed here, airlines can determine the optimal load factor threshold and seating arrangement strategy to improve economic benefits and reduce the probability of passenger infection.

by Syed Abdul Hamid, Md. Ragaul Azim, Md. Mahfujur Rahman, Md. Sirajul Islam Background The COVID-19 pandemic has highlighted the importance of a well-equipped and supported healthcare workforce, and Bangladesh still faces challenges in providing adequate and well-equipped healthcare services. Therefore, the study aims to assess the level of working conditions of the clinical health workers in Bangladesh and their relative importance in delivering quality healthcare services. Methods The study followed a cross-sectional study design and collected primary data adopting a quantitative method. A total of 319 clinical workforces from four districts and eight sub-districts were randomly selected using a multi-stage sampling technique. A 26-component questionnaire used to assess various components of working conditions. Descriptive statistics, and bivariate analysis were used to analyze the data. Results The study found that the working conditions of clinical health workers in primary and secondary healthcare facilities in Bangladesh were quite poor (3.40), with almost two-thirds of respondents showing negative views in 23 out of 26 indicators. The results also showed that working conditions were significantly (p ≤ 0.05) higher in primary compared to secondary level facilities. Moreover, men, younger workforce, and workforce with shorter length of service were more likely to report poor working conditions than their counterparts. Lastly, receiving monthly salary in due time was top-ranked (99.15) in terms of importance for delivering quality healthcare, followed by availability of medicines (98.04), and medical and surgical requisites (97.57), and adequate mentoring and support to perform duties (97.50). Conclusion The study highlights the poor working conditions of clinical health workers in public health facilities in Bangladesh. It recommends that policymakers should prioritize improving working conditions by addressing the factors that are crucial for delivering quality healthcare. Improving working conditions will have a positive impact on the retention and motivation of workers, which will ultimately lead to better health outcomes for the population. …

by Kathryn W. Hendrickson, Ramona O. Hopkins, Danielle L. Groat, Stephanie C. Stokes, Fiona M. Schroeder, Jorie M. Butler, Eliotte L. Hirshberg Introduction Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2,) caused an influx of patients with acute disease characterized by a variety of symptoms termed COVID-19 disease, with some patients going on to develop post-acute COVID-19 syndrome. Individual factors like sex or coping styles are associated with a person’s disease experience and quality of life. Individual differences in coping styles used to manage COVID-19 related stress correlate with physical and mental health outcomes. Our study sought to understand the relationship between COVID-19 symptoms, severity of acute disease, and coping profiles. Methods An online survey to assess symptoms, functional status, and recovery in a large group of patients was nationally distributed online. The survey asked about symptoms, course of illness, and included the Brief-COPE and the adapted Social Relationship Inventory. We used descriptive and cluster analyses to characterize patterns of survey responses. Results 976 patients were included in the analysis. The most common symptoms reported by the patients were fatigue (72%), cough (71%), body aches/joint pain (66%), headache (62%), and fever/chills (62%). 284 participants reported PACS. We described three different coping profiles: outward, inward, and dynamic copers. Discussion Fatigue, cough, and body aches/joint pains were the most frequently reported symptoms. PACS patients were sicker, more likely to have been hospitalized. Of the three coping profiles, outward copers were more likely to be admitted to the hospital and had the healthiest coping strategies. Dynamic copers activated several coping strategies both positive and negative; they were also younger and more likely to report PACS. Conclusion Cough, fatigue, and body aches/joint pain are common and most important to patients with acute COVID-19, while shortness of breath defined the experience for patients with PACS. Of the three coping profiles, dynamic copers were more likely to report PACS. Additional investigations into coping profiles in general, and the experience of COVID-19 and PACS is needed. …

Abstract Background Malaria is a leading cause of death and reduced life span in Guinea and Sierra Leone, where plans for rolling out the malaria vaccine for children are being made. There is little evidence about caregiver acceptance rates to guide roll-out policies. To inform future vaccine implementation planning, this analysis aimed to assess potential malaria vaccine acceptance by caregivers and identify factors associated with acceptance in Guinea and Sierra Leone. Methods A cross-sectional household survey using lot quality assurance sampling was conducted in three regions per country between May 2022 and August 2022. The first survey respondent in each household provided sociodemographic information. A household member responsible for childcare shared their likelihood of accepting a malaria vaccine for their children under 5 years and details about children’s health. The prevalence of caregiver vaccine acceptance was calculated and associated factors were explored using multivariable logistic regression modelling calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results Caregivers in 76% of 702 sampled households in Guinea and 81% of 575 households in Sierra Leone were accepting of a potential vaccine for their children. In both countries, acceptance was lower in remote areas than in urban areas (Guinea: aOR 0.22 [95%CI 0.09–0.50], Sierra Leone: 0.17 [0.06–0.47]). In Guinea, acceptance was lower among caregivers living in the richest households compared to the poorest households (0.10 [0.04–0.24]), among those whose children were tested for malaria when febrile (0.54 [0.34–0.85]) and in households adopting more preventative measures against malaria (0.39 [0.25–0.62]). Better knowledge of the cause of malaria infection was associated with increased acceptance (3.46 [1.01–11.87]). In Sierra Leone, vaccine acceptance was higher among caregivers living in households where the first respondent had higher levels of education as compared to lower levels (2.32 [1.05–5.11]). Conclusion In both countries, malaria vaccine acceptance seems promising for future vaccine roll-out programmes. Policy makers might consider regional differences, sociodemographic factors, and levels of knowledge about malaria for optimization of implementation strategies. Raising awareness about the benefits of comprehensive malaria control efforts, including vaccination and other preventive measures, requires attention in upcoming campaigns. …

AbstractBackgroundPre-existing immunity, including memory B-cells and pre-existing antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether pre-existing hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163-antibodies) could affect antibody responses following vaccination with A/California/07/2009-like (CA/09) A(H1N1)pdm09 influenza viruses in humans.MethodsPre- and post-vaccination sera collected from 300 adults (birth year:1961-1998) in 6 seasons (2010-2016) were analyzed using HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the pre-existing K163-antibody-mediated suppression effect.ResultsPre-existing K163-antibody titers of ≥80 affected HAI antibody responses following influenza vaccination containing CA/09-like antigens. At high K163-antibody concentrations (HAI antibody titers≥160), all HAI antibody responses were suppressed, while at moderate K163-antibody concentrations (HAI antibody titer=80), only K163-epitope-specific antibody responses were suppressed and novel HAI antibody responses targeting the non-K163-epitope(s) were induced by vaccination. Novel antibodies targeting non-K163 epitope(s) cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation, rather than historic 1977-2007 A(H1N1) viruses.ConclusionK163-antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how pre-existing antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.

Abstract Purpose Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known. Methods Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values. Results In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747–0.880) and 0.784 (0.691–0.855), respectively. Conclusion SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero. …

Abstract Purpose Cladophialophora bantiana is a wonted melanized fungus causing brain abscess. In past many cases were reported from Asia, particularly from India. Of late, there is a rise in cases in places besides Asia and hence a review of the cases is warranted. Methods We present a case of fatal cerebral phaeohyphomycosis caused by C. bantiana and conduct a systematic review of culture confirmed brain abscess due to C. bantiana reported between 2015 and 2022. Results Of the 39 cases found, majority (68%) were immunocompromised. The various clinical presentations were headache (53%), hemiparesis (34%), visual disturbance (25%), altered sensorium (18%), aphasia/dysarthria (12%) and seizures (9%). Isolated lesion was observed in 18 (60%) patients. In the sequence of occurrence, the lesions were in frontal (30%), temporal (27%) and parietal (20%) region. There were five cases with coinfections such as concurrent detection of Nocardia pneumonia in two cases, toxoplasma DNA in brain abscess, coexisting pulmonary Cryptococcus neoformans infection and coexisting Candida in a case of brain abscess in one case each. Surgical intervention was performed in 84% cases. Antifungal therapy included voriconazole (80%), liposomal amphotericin B (76%), 5-fluorocytosine (30%), posaconazole (10%), and amphotericin B deoxycholate (6%). The overall mortality was 50% with lower mortality (42%) in regions outside Asia compared to Asia (63.6%) though not statistically significant. Conclusions C. bantiana brain abscess is an emerging infection worldwide. Next generation sequencing is an upcoming promising diagnostic test. Early complete excision of the lesion with effective antifungals may improve the outcome. …

Abstract Introduction Soluble urokinase plasminogen activator receptor (suPAR) is a biologically active protein and increased levels are associated with worse outcomes in critically ill patients. suPAR in bronchoalveolar fluid (BALF) may be helpful to differentiate between types of acute respiratory distress syndrome (ARDS) and may have potential for early detection of fungal infection. Methods We prospectively investigated levels of suPAR in BALF and serum in critically ill patients who underwent bronchoscopy for any reason at the ICU of the Department of Internal Medicine, Medical University of Graz, Graz, Austria. Results Seventy-five patients were available for analyses. Median age was 60 [25th–75th percentile: 50–69] years, 27% were female, and median SOFA score was 12 [11–14] points. Serum suPAR levels were significantly associated with ICU mortality in univariable logistic regression analysis. There was no correlation between BALF and serum suPAR. Serum suPAR was higher in ARDS patients at 11.2 [8.0–17.2] ng/mL compared to those without ARDS at 7.1 [3.7–10.1] (p 

Abstract Purpose Clinical and direct medical cost data on RSV-related hospitalizations are relevant for public health decision-making. We analyzed nationwide data on RSV-coded hospitalizations from Germany in different age and risk groups. Methods Assessment of RSV-coded hospitalizations (ICD-10-GM RSV code J12.1/J20.5/J21.0 as primary discharge diagnosis) from 01/2010 to 12/2019, using remote data retrieval from the Hospital Statistics Database of the German Federal Statistical Office. Results Overall, 130,084 RSV-coded hospitalizations (123,091 children  59 years) were reported (median age 

Infection and Immunity, Ahead of Print.

Abstract Background Both tuberculosis (TB) and diabetes mellitus (DM) are major public health problems threatening global health. TB patients with DM have a higher bacterial burden and affect the absorption and metabolism for anti-TB drugs. Drug-resistant TB (DR-TB) with DM make control TB more difficult. Methods This study was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. We searched PubMed, Excerpta Medica Database (EMBASE), Web of Science, ScienceDirect and Cochrance Library for literature published in English until July 2022. Papers were limited to those reporting the association between DM and treatment outcomes among DR-TB and multidrug-resistant TB (MDR-TB) patients. The strength of association was presented as odds ratios (ORs) and their 95% confidence intervals (CIs) using the fixed-effects or random-effects models. This study was registered with PROSPERO, number CRD: 42,022,350,214. Results A total of twenty-five studies involving 16,905 DR-TB participants were included in the meta-analysis, of which 10,124 (59.89%) participants were MDR-TB patients, and 1,952 (11.54%) had DM history. In DR-TB patients, the pooled OR was 1.56 (95% CI: 1.24–1.96) for unsuccessful outcomes, 0.64 (95% CI: 0.44–0.94) for cured treatment outcomes, 0.63 (95% CI: 0.46–0.86) for completed treatment outcomes, and 1.28 (95% CI: 1.03–1.58) for treatment failure. Among MDR-TB patients, the pooled OR was 1.57 (95% CI: 1.20–2.04) for unsuccessful treatment outcomes, 0.55 (95% CI: 0.35–0.87) for cured treatment outcomes, 0.66 (95% CI: 0.46–0.93) for treatment completed treatment outcomes and 1.37 (95% CI: 1.08–1.75) for treatment failure. Conclusion DM is a risk factor for adverse outcomes of DR-TB or MDR-TB patients. Controlling hyperglycemia may contribute to the favorite prognosis of TB. Our findings support the importance for diagnosing DM in DR-TB /MDR-TB, and it is needed to control glucose and therapeutic monitoring during the treatment of DR-TB /MDR-TB patients. …

Abstract Background The organ dysfunction that is associated with death in COVID-19 patients has not been determined in multicenter epidemiologic studies. In this study, we evaluated the major association with death, concomitant organ dysfunction, and proportion of multiple organ failure in deaths in patients with COVID-19, along with information on organ support. Methods We performed an observational cohort study using the Japanese multicenter research of COVID-19 by assembling a real-world data (J-RECOVER) study database. This database consists of data on patients discharged between January 1 and September 31, 2020, with positive SARS-CoV-2 test results, regardless of intensive care unit admission status. These data were collected from the Diagnosis Procedure Combination and electronic medical records of 66 hospitals in Japan. The clinician identified and recorded the organ responsible for the death of COVID-19. Results During the research period, 4,700 patients with COVID-19 were discharged from 66 hospitals participating in the J-RECOVER study; of which, 272 patients (5.8%) from 47 institutions who died were included in this study. Respiratory system dysfunction (87.1%) was the leading association with death, followed by cardiovascular (4.8%), central nervous (2.9%), gastrointestinal (2.6%), and renal (1.1%) dysfunction. Most patients (96.7%) who died of COVID-19 had respiratory system damage, and about half (48.9%) had multi-organ damage. Of the patients whose main association with death was respiratory dysfunction, 120 (50.6%) received mechanical ventilation. Conclusion This study showed that although respiratory dysfunction was the most common association with death in many cases, multi-organ dysfunction was associated with death due to COVID-19. …

Volume 14, Issue 1, December 2023 .

Clinical Microbiology Reviews, Ahead of Print.

ObjectivesAs countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation. DesignSystematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa. Data sourcesPubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences. Eligibility criteriaClinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure. Data extraction and synthesisWe captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature. ResultsOf 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret. ConclusionsThe proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%–50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure. PROSPERO registration numberCRD42022324136. …

ObjectivesWe aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and patient preferences for cardiovascular care and education. DesignA prospective observational study. SettingThis study was conducted at the Majengo HIV Care and Treatment Clinic, an outpatient government-funded clinic in Moshi, Tanzania ParticipantsAdult patients presenting to an HIV clinic for routine care in northern Tanzania were enrolled from 1 September 2020 to 1 March 2021. InterventionsAt enrolment, participants completed a survey and a resting 12-lead ECG was obtained. At 6 month follow-up, a repeat survey regarding interim health events and repeat ECG was obtained. Primary and secondary outcome measuresInterim major adverse cardiovascular events (MACE) were defined by: self-reported interim stroke, self-reported hospitalisation for heart failure, self-reported interim myocardial infarction, interim myocardial infarction by ECG criteria (new pathologic Q waves in two contiguous leads) or death due to cardiovascular disease (CVD). ResultsOf 500 enrolled participants, 477 (95.4%) completed 6 month follow-up and 3 (0.6%) died. Over the 6 month follow-up period, 11 MACE occurred (3 strokes, 6 myocardial infarctions, 1 heart failure hospitalisation and 1 cardiovascular death), resulting in an incidence rate of 4.58 MACE per 100 person-years. Of participants completing 6 month follow-up, 31 (6.5%) reported a new non-communicable disease diagnosis, including 23 (4.8%) with a new hypertension diagnosis. ConclusionsThe incidence of MACE among PLWH in Tanzania is high. These findings are an important preliminary step in understanding the landscape of CVD among PLWH in Tanzania and highlight the need for interventions to reduce cardiovascular risk in this population. …

ObjectiveTo assess if the antecedent statin use was associated with all-cause death among COVID-19 patients enrolled in Medicaid. DesignCohort study. SettingMississippi Medicaid population. ParticipantsThis study included 10 792 Mississippi Medicaid-enrolled patients between 18 and 64 years of age with a confirmed COVID-19 diagnosis from March 2020 to June 2021. InterventionAntecedent statin use, which was determined by a record of statin prescription in the 90-day period prior to the COVID diagnosis. Main outcome measuresThe outcomes of interest included mortality from all cause within 30 days, 60 days and 90 days after index. ResultsA total of 10 792 patients with COVID-19 met the inclusion and exclusion criteria, with 13.1% of them being antecedent statin users. Statin users were matched 1:1 with non-users based on age, sex, race, comorbidities and medication use by propensity score matching. In total, the matched cohort consisted of 1107 beneficiaries in each group. Multivariable logistic regression showed that statin users were less likely to die within 30 days (adjusted OR: 0.51, 95% CI: 0.32 to 0.83), 60 days (OR: 0.56, 95% CI: 0.37 to 0.85) and 90 days (OR: 0.55, 95% CI: 0.37 to 0.82) after diagnosis of COVID-19. Those with low-intensity/moderate-intensity statin use had significantly lower mortality risk in the 60-day and the 90-day follow-up period, while the high intensity of statin use was only found to be significantly associated with a lower odd of mortality within 30 days post index. ConclusionAfter COVID infection, Medicaid beneficiaries who had taken statins antecedently could be at lower risk for death. For patients with chronic conditions, continuity of care is crucial when interruptions occur in their medical care. Further research is required to further investigate the potential mechanisms and optimal use of statins in COVID-19 treatment. …

IntroductionSciatica can be very painful and, in most cases, is due to pressure on a spinal nerve root from a disc herniation with associated inflammation. For some patients, the pain persists, and one management option is a spinal epidural steroid injection (ESI). The aim of an ESI is to relieve leg pain, improve function and reduce the need for surgery. ESIs work well in some patients but not in others, but we cannot identify these patient subgroups currently. This study aims to identify factors, including patient characteristics, clinical examination and imaging findings, that help in predicting who does well and who does not after an ESI. The overall objective is to develop a prognostic model to support individualised patient and clinical decision-making regarding ESI. MethodsPOiSE is a prospective cohort study of 439 patients with sciatica referred by their clinician for an ESI. Participants will receive weekly text messages until 12 weeks following their ESIand then again at 24 weeks following their ESI to collect data on leg pain severity. Questionnaires will be sent to participants at baseline, 6, 12 and 24 weeks after their ESI to collect data on pain, disability, recovery and additional interventions. The prognosis for the cohort will be described. The primary outcome measure for the prognostic model is leg pain at 6 weeks. Prognostic models will also be developed for secondary outcomes of disability and recovery at 6 weeks and additional interventions at 24 weeks following ESI. Statistical analyses will include multivariable linear and logistic regression with mixed effects model. Ethics and disseminationThe POiSE study has received ethical approval (South Central Berkshire B Research Ethics Committee 21/SC/0257). Dissemination will be guided by our patient and public engagement group and will include scientific publications, conference presentations and social media. …

IntroductionThe post-COVID-19 pandemic era has seen a rise in ‘quiet quitting’, with employees limiting their efforts to fulfil assigned tasks without going beyond their designated responsibilities. The occurrence of quiet quitting in hospitals can have detrimental effects not only on organisational culture but also on patient safety and satisfaction. Therefore, the aim of this study is to define quiet quitting among healthcare professionals in hospitals through concept analysis, identify the associated factors and outcomes of quiet quitting, and conduct a scoping review based on this defined concept. Methods and analysisThis study will adopt Walker and Avant method for concept analysis and Aromataris and Munn methodological framework as well as the Joanna Briggs Institute Reviewer’s manual for scoping reviews. The concept analysis will follow eight steps: (1) choosing the concept; (2) outlining the objectives of the analysis; (3) recognising the concept’s uses; (4) selecting the concept’s defining attributes; (5) constructing a model case; (6) constructing additional cases; (7) defining the consequences and antecedents of the concept; and (8) determining empirical referents. This study used databases of PubMed, Embase, PsycINFO, Scopus, ProQuest Dissertations and Theses Global for the English language, and NDSL, KCI, RISS, KISS and DBpia for the Korean language. Additionally, grey literature will be searched. Ethics and disseminationThis concept analysis and scoping review does not require ethical approval. The results of this study will be reported in peer-reviewed publications. …

Abstract Background Ultrasensitive rapid diagnostic test (usRDT) was recently developed to improve the detection of low-density Plasmodium falciparum infections. However, its diagnostic performance has not been evaluated in the Democratic Republic of Congo (DRC). This study aims to determine the performance of the usRDT in malaria diagnosis in asymptomatic individuals under field condition in Kisangani, Northeast of DRC. Methods A community-based cross-sectional study was carried out from June to August 2022 on 312 asymptomatic individuals residing in the city of Kisangani. Capillary blood samples were collected by finger prick for microscopic examination of thick and thin blood film, RDTs, and nested polymerase chain reaction (PCR). Alere™ Malaria Ag P.f usRDT and conventional RDT (cRDT/SD Bioline Malaria Ag P.f) kits were used for the detection of Plasmodium histidine rich protein 2 (HRP2) antigen as a proxy for the presence of P. falciparum. The diagnostic performance of the usRDT was compared with cRDT, microscopy and PCR. Results The prevalence of asymptomatic P. falciparum malaria was 40.4%, 42.0%, 47.1% and 54.2% by cRDT, microscopy, usRDT and PCR, respectively. By using PCR as a reference, usRDT had sensitivity and specificity of 87.0% (95% CI 81.4–91.7) and 100.0% (95% CI 97.5–100.0), respectively, whereas the cRDT had sensitivity and specificity of 74.6% (95% CI 67.3–80.9) and 100% (95% CI 97.1–100.0), respectively. By using microscopy as a reference, usRDT had sensitivity and specificity of 96.9% (95% CI 92.4–99.2) and 89.0% (95% CI 83.5–93.1), respectively, while the cRDT had sensitivity and specificity of 96.2% (95% CI 92.3–98.7) and 100% (95% CI 97.9–100.0), respectively. Conclusion The usRDT showed better diagnostic performance with higher sensitivity than the cRDT which is currently in use as point-of-care test. Further research is necessary to assess the access and cost-effectiveness of the usRDTs to use for malaria surveillance. …

Abstract Background Urinary tract infections (UTI) in men differ relevantly to women by their pathogens. Gram-positive uropathogens play a relevant role in UTI in men. In this study, we aimed to analyze the epidemiology of Enterococcus faecalis in UTI in male outpatients. Methods We conducted a retrospective observational multicenter study during 2015 to 2020 consisting of urine samples of 99,415 adult male outpatients sent from 6,749 outpatient practices from Germany. Proportions were compared using the z-Test and 95% confidence intervals were calculated using the Clopper-Pearson method. Results E. faecalis is the 2nd most frequent bacteria (16%) detected in suspected UTI in male outpatients. Young men are predominantly at risk (17%) for isolation of E. faecalis in suspected UTI. In polymicrobial infections E. faecalis is isolated in 47% of all suspected UTI in men. Recurrency of suspected UTI is significantly more frequent when E. faecalis is isolated compared to Escherichia coli (22% vs 26%; p 

Publication date: Available online 18 November 2023 Source: Infectious Disease Modelling Author(s): Jia-Lin Wang, Xin-Long Xiao, Fen-Fen Zhang, Xin Pei, Ming-Tao Li, Ju-Ping Zhang, Juan Zhang, Gui-Quan Sun …

AbstractPreexisting immunity against influenza viruses has long been known to regulate the magnitude and specificity of vaccine-induced humoral immunity. In this manuscript by Lu et al., the authors highlight how varying levels of preexisting antibodies against a single site on hemagglutinin impact vaccine-induced antibody responses. This commentary discusses the essential findings and implications of the study, emphasizing the importance of understanding how preexisting antibodies suppress the diversification of humoral immunity and how next generation vaccine strategies can overcome preexisting immunity to generate immunity against ever-evolving influenza viruses.

AbstractCOVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat–containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed that NLRP12 directly interacted with the M protein through its leucine-rich repeat domain. Moreover, in vitro studies demonstrated that NLRP12 interacted with TRAF3 and promoted its ubiquitination and degradation, which counteracted the inhibitory effect of TRAF3 on the NF-κB/MAPK signaling pathway and promoted the production of inflammatory cytokines. Furthermore, an in vivo study revealed that NLRP12 knockout mice displayed attenuated tissue injury and ameliorated inflammatory responses in the lungs when infected with a SARS-CoV-2 M protein–reconstituted pseudovirus and mouse coronavirus. Taken together, these findings suggest that NLRP12 mediates the inflammatory responses during coronavirus infection.

Invasive fungal infections pose a major threat to human health. Bacterial and protozoan pathogens secrete protein effectors that overcome innate immune barriers to promote microbial colonization, yet few such molecules have been identified in human fungal pathogens. Recent studies have begun to reveal these long-sought effectors and have illuminated how they subvert key cellular pathways, including apoptosis, myeloid cell polarization, Toll-like receptor signaling, and phagosome action. Thus, despite lacking the specialized secretion systems of bacteria and parasites, it is increasingly clear that fungi independently evolved effectors targeting pathways often subverted by other classes of pathogens. These findings demonstrate the remarkable power of convergent evolution to enable diverse microbes to infect humans while also setting the stage for detailed dissection of fungal disease mechanisms.

Abstract Purpose Cladophialophora bantiana is a wonted melanized fungus causing brain abscess. In past many cases were reported from Asia, particularly from India. Of late, there is a rise in cases in places besides Asia and hence a review of the cases is warranted. Methods We present a case of fatal cerebral phaeohyphomycosis caused by C. bantiana and conduct a systematic review of culture confirmed brain abscess due to C. bantiana reported between 2015 and 2022. Results Of the 39 cases found, majority (68%) were immunocompromised. The various clinical presentations were headache (53%), hemiparesis (34%), visual disturbance (25%), altered sensorium (18%), aphasia/dysarthria (12%) and seizures (9%). Isolated lesion was observed in 18 (60%) patients. In the sequence of occurrence, the lesions were in frontal (30%), temporal (27%) and parietal (20%) region. There were five cases with coinfections such as concurrent detection of Nocardia pneumonia in two cases, toxoplasma DNA in brain abscess, coexisting pulmonary Cryptococcus neoformans infection and coexisting Candida in a case of brain abscess in one case each. Surgical intervention was performed in 84% cases. Antifungal therapy included voriconazole (80%), liposomal amphotericin B (76%), 5-fluorocytosine (30%), posaconazole (10%), and amphotericin B deoxycholate (6%). The overall mortality was 50% with lower mortality (42%) in regions outside Asia compared to Asia (63.6%) though not statistically significant. Conclusions C. bantiana brain abscess is an emerging infection worldwide. Next generation sequencing is an upcoming promising diagnostic test. Early complete excision of the lesion with effective antifungals may improve the outcome. …

The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, including dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances or neurocognitive complaints.

Abstract The central nervous system is one of the most common sites of aspergillosis involvement in immunocompromised people, just after sinopulmonary infections. Neuroimaging modalities are crucial for the diagnosis of cerebral aspergillosis (CA). Here, we describe a rare case of concurrent mixed aspergillosis infection with Aspergillus fumigatus and Aspergillus niger in a 2-year-old leukemic boy. The first neuroimaging finding, which was followed by focal seizures, was recognized as extensive cerebral hemorrhage in the absence of thrombocytopenia and coagulopathy. As the patient survived for more than 4 months after diagnosis, we were able to perform a neuroimaging evaluation during long-term observation. In serial neuroimaging studies, a secondary fungal abscess was observed at the site of hemorrhagic infarctions. Finally, the patient died from bacterial sepsis. In this case study, we try to categorize the neuroimaging findings of CA into distinct phases to better understand how CA changes over time. …

OBJECTIVES: Diagnosis of pneumonia is challenging in critically ill, intubated patients due to limited diagnostic modalities. Endotracheal aspirate (EA) cultures are standard of care in many ICUs; however, frequent EA contamination leads to unnecessary antibiotic use. Nonbronchoscopic bronchoalveolar lavage (NBBL) obtains sterile, alveolar cultures, avoiding contamination. However, paired NBBL and EA sampling in the setting of a lack of gold standard for airway culture is a novel approach to improve culture accuracy and limit antibiotic use in the critically ill patients. DESIGN: We designed a pilot study to test respiratory culture accuracy between EA and NBBL. Adult, intubated patients with suspected pneumonia received concurrent EA and NBBL cultures by registered respiratory therapists. Respiratory culture microbiology, cell counts, and antibiotic prescribing practices were examined. SETTING: We performed a prospective pilot study at the Cleveland Clinic Main Campus Medical ICU in Cleveland, Ohio for 22 months from May 2021 through March 2023. PATIENTS OR SUBJECTS: Three hundred forty mechanically ventilated patients with suspected pneumonia were screened. Two hundred fifty-seven patients were excluded for severe hypoxia (Fio2 ≥ 80% or positive end-expiratory pressure ≥ 12 cm H2O), coagulopathy, platelets less than 50,000, hemodynamic instability as determined by the treating team, and COVID-19 infection to prevent aerosolization of the virus. INTERVENTIONS: All 83 eligible patients were enrolled and underwent concurrent EA and NBBL. MEASUREMENTS AND MAIN RESULTS: More EA cultures (42.17%) were positive than concurrent NBBL cultures (26.51%, p = 0.049), indicating EA contamination. The odds of EA contamination increased by eight-fold 24 hours after intubation. EA was also more likely to be contaminated with oral flora when compared with NBBL cultures. There was a trend toward decreased antibiotic use in patients with positive EA cultures if paired with a negative NBBL culture. Alveolar immune cell populations were recovered from NBBL samples, indicating successful alveolar sampling. There were no major complications from NBBL. CONCLUSIONS: NBBL is more accurate than EA for respiratory cultures in critically ill, intubated patients. NBBL provides a safe and effective technique to sample the alveolar space for both clinical and research purposes.

Journal of Medical Virology, Volume 95, Issue 11, November 2023.

SARS-CoV-2 transmission and epidemic potential has been associated with population’ immunity levels [1]–[6]. Prior to the emergence of newer variants of concern (VOC), COVID-19 incidence and number of deaths in Vietnam were substantially lower than those in Southeast Asia, and the country had ranked as one of the best in terms of its COVID-19 response. The low rates of infection until 2020 have been attributed to successful movement control orders (MCOs) restricting movement within national and international borders in Vietnam.

Nocardia spp. cause invasive infections around the world; awareness of effective antimicrobial drugs is crucial. …

Table of Contents for Volume 29, Number 12-December 2023 …

Research - Detection of Anopheles stephensi Mosquitoes by Molecular Surveillance, Kenya…

Dispatch - Autochthonous Dengue Outbreak, Paris Region, France, September-October 2023…

Children in households reliant on domestic wells may experience increased risks for exposure. …

Tropical Medicine &International Health, Volume 28, Issue S1, Page 3-368, November 2023.

Tropical Medicine &International Health, Volume 28, Issue S1, Page 369-389, November 2023.

Tropical Medicine &International Health, Volume 28, Issue S1, Page 390-407, November 2023.

Tropical Medicine &International Health, Volume 28, Issue S1, Page 1-2, November 2023.

HIVCabotegravirinjection site reactionlong-acting antiretroviral drugs…

AbstractLarge language models (LLMs) are artificial intelligence systems trained by deep learning algorithms to process natural language and generate text responses to user prompts. Some approach physician performance on a range of medical challenges, leading some proponents to advocate for their potential use in clinical consultation and prompting some consternation about the future of cognitive specialties. However, LLMs currently have limitations that preclude safe clinical deployment in performing specialist consultations, including frequent confabulations, lack of contextual awareness crucial for nuanced diagnostic and treatment plans, inscrutable and unexplainable training data and methods, and propensity to recapitulate biases. Nonetheless, considering the rapid improvement in this technology, growing calls for clinical integration, and healthcare systems that chronically undervalue cognitive specialties, it is critical that infectious diseases clinicians engage with LLMs to enable informed advocacy for how they should—and shouldn’t—be used to augment specialist care.

Strange are the opportunities that presented themselves and where the path led during the coronavirus disease 2019 (COVID-19) pandemic. It all began when I was at a National Institutes of Health (NIH) study section on 5–6 March 2020 in Washington, DC, expecting to fly to Boston for the Conference on Retroviruses and Opportunistic Infections (CROI) when a Friday email announced the cancellation of in-person attendance at the conference (wisely). I had been looking forward to CROI, having worked for weeks to get visa appointments for two Ugandan scientists to travel to CROI to present their cryptococcal meningitis abstracts. My team makes an effort always to present cryptococcal abstracts at CROI so that people do not forget that opportunistic infections still exist worldwide. In March 2020, we were excited to have just launched a phase 2 trial to test oral amphotericin B formulation for cryptococcal meningitis.