Nyt fra tidsskrifterne

Abstract Background Malaria remains the leading cause of mortality and morbidity in young children in sub-Saharan Africa. To prevent malaria in children living in moderate-to-high malaria transmission areas, the World Health Organization has recommended perennial malaria chemoprevention (PMC). Prior to piloting PMC implementation in southern Togo, a household survey was conducted to estimate malaria infection prevalence in children under 2 years of age (U2). Methods A cross-sectional community-based household survey was conducted in the Haho district in the Togo Plateaux region. A three-stage random sampling method was used to select study participants aged 10–23 months whose caretakers gave informed consent. The prevalence of Plasmodium infection, defined as a positive rapid diagnostic test (RDT), was estimated with 95% confidence interval (CI). Clinical malaria was defined as having a positive RDT plus fever (≥ 37.5 °C) or history of fever in the last 24 h. Mixed-effects logistic regression models were used to assess the child’s, caretaker’s, and household’s factors associated with malaria infection. Results A total of 685 children were included in the survey conducted January–February in 2022 (dry season). Median age was 17 months (interquartile range: 13–21). About 80% of the children slept under a bed net the night before the interview. Malaria infection prevalence was 32.1% (95% CI 27.7–37.0) with significant area variation (cluster range: 0.0–73.3). Prevalence of clinical malaria was 15.4% (95% CI 12.2–19.2). Children whose caretakers were animist (aOR: 1.71, 95% CI 1.19–2.46) and those living in mother-headed households (aOR: 2.39, 95% CI 1.43–3.99) were more likely to have a positive RDT. Living more than 5 km away from the nearest health facility (aOR: 1.60, 95% CI 1.04–2.44) and presence of two or more under-5-years children in the household (aOR: 1.44, 95% CI 1.01–2.07) were also associated with increased risk of infection. Conclusion One-third of the children U2 who participated in this survey had malaria infection, thus PMC could be a promising strategy to reduce malaria burden in young children in Plateaux region. Reinforcement of outreach services and targeting the poorest households should be prioritized to reduce the inequity in malaria prevention in children exposed to the infection. …

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. …

Visceral leishmaniasis (VL) is a systemic infection caused by vector-borne protozoans; in southern Europe VL is caused by parasites belonging to the Leishmania infantum species [1]. Immunocompromised individuals, including transplant recipients, are at risk for severe VL with high rate of relapses [2]. In transplant recipients, asymptomatic Leishmania infection can reactivate during the immunosuppressive therapy and promote the resurgence of clinically evident leishmaniasis; thus, screening asymptomatically infected patients could be beneficial.

To the Editor A recent randomized clinical trial found that antibiotic treatment had minimal benefit for children with acute sinusitis who did not present with nasopharyngeal bacterial pathogens. The authors suggested that testing for specific bacteria on presentation could be a strategy to reduce unnecessary antibiotic use in this condition.

To the Editor A recent JAMA Insights article reviewed indications for Pneumocystis jirovecii pneumonia prophylaxis in immunocompromised adults. The authors commented that patients receiving corticosteroids at doses equivalent to at least 20 mg/d of prednisone for at least 4 weeks who have an additional cause of immunosuppression should receive Pneumocystis pneumonia (PCP) prophylaxis. They also noted there is no consensus for when to initiate PCP prophylaxis among patients with autoimmune disease. Unfortunately, without consensus and with no clear definition of “additional cause of immunosuppression,” confusion may arise regarding the appropriateness of PCP prophylaxis in individual cases. To help decide whether PCP prophylaxis for patients with autoimmune disease is indicated, clinicians can consider the number needed to treat (NNT) to prevent 1 episode of PCP balanced against the number needed to harm (NNH) (ie, occurrence of serious adverse drug reactions resulting from prophylaxis with trimethoprim-sulfamethoxazole). In a systematic review of patients with malignancies, a PCP risk greater than or equal to 6.2% determined the threshold for prophylaxis, likely exceeding the PCP risk among patients with certain autoimmune disorders (eg, the incidence of PCP was calculated to be 0.1% among patients with autoimmune blistering disorders). Among patients with cancer, the NNT was 19 to prevent 1 case of PCP. In a study of patients with rheumatic disease receiving greater than 30 mg/d of prednisone for more than 4 weeks, PCP risk was higher for certain diseases, including microscopic polyangiitis and dermatomyositis, and for initial prednisone doses of greater than 60 mg/d. The NNT for patients receiving a prednisone dose greater than 60 mg/d was 32, whereas the NNT was 215 among patients receiving more than 30 mg/d of prednisone, which is higher than the NNH of 131. In another study of patients with rheumatologic illnesses receiving lower doses of corticosteroids, the NNT for patients receiving greater than or equal to 15 mg/d and less than 30 mg/d of prednisone or the equivalent was 204, exceeding the NNH of 45. However, the NNT fell to 31 for a “high-risk” subgroup, defined as patients with baseline lymphopenia or receiving pulse-dose steroids. It is unknown whether these calculations can be extended to other autoimmune diseases or to patients receiving corticosteroids in combination with newer, targeted biologic therapies, which may be less immunosuppressive. Although steroids are an established risk factor for PCP, there is heterogeneity in the risk conferred by the underlying disease, concomitant immunosuppressive therapies, and patient comorbidities. When available, the NNT and NNH can inform decision-making regarding PCP prophylaxis. When unavailable, careful consideration of the abovementioned factors, in addition to corticosteroid dose and duration, may enable clinicians to balance the risk and benefit of administering PCP prophylaxis.

In Reply Mr Meng and colleagues express concern that testing for H influenzae, S pneumoniae, and M catarrhalis, which are frequently found to colonize the nasal passages of well children, might lead to increased antibiotic use. However, this will occur only if the results from our trial are applied indiscriminately to a population that was not included in our study.

In Reply We agree with Dr Caplan and colleagues that NNTs, where available, can guide decision-making regarding PCP prophylaxis for the heterogeneous group of patients with autoimmune disease, as discussed in their Letter regarding our JAMA Insights article. However, the utility of NNT is limited for several reasons.

A study linking viral infection with reduced levels of serotonin, a neurotransmitter involved in learning, memory, and mood, has proposed a new potential mechanism underlying post–COVID-19 condition. Also known as long COVID, the condition involves symptoms such as fatigue, memory loss, and cognitive impairment.

A multidrug-resistant strain of Pseudomonas aeruginosa bacteria may be circulating in southern California, researchers reported in Emerging Infectious Diseases.

Although the US Strategic National Stockpile—a collection of medications, medical devices, and vaccines, among other tools—distributed supplies such as personal protective equipment within the first 3 months of 2020, its ability to respond effectively to the COVID-19 pandemic fell short due to internal and external factors, according to an audit conducted by the Department of Health and Human Services (HHS) Office of Inspector General. Due to these factors, “the Stockpile could not meet demand and was not equipped to handle the COVID-19 pandemic,” the investigators concluded.

Although the rates of medical abortions were similar before and after the start of the COVID-19 pandemic, the rate of procedural abortions fell by 31%, according to commercial insurance reimbursement data from about 17 500 abortions. The study was funded by the federal Health Resources and Services Administration.

IntroductionLow back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines. Methods and analysisThis is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient–participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient–participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned. Ethics and disseminationThe trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publications in journals, media and conference presentations. Trial registration numberACTRN12622001505796. …

ObjectiveThis study aimed at evaluating refractive changes in German school-aged children before and after the COVID-19 pandemic. DesignCross-sectional study. Setting414 eye care professional centres from Germany. ParticipantsRefractive data from 59 926 German children aged 6–15 years were examined over a 7-year period (2015–2021). Primary and secondary outcome measuresSpherical equivalent refraction was assessed as a function of year, age and gender. The refractive values concerning 2020 and 2021 were compared with those assigned to prior years (2015–2019). ResultsThe refractive data associated with 2020 and 2021 showed a myopic refractive shift of approximately –0.20D compared with the 2015–2019 range. The refractive change was statistically considerable in the 6 to 11-year range (p

ObjectivesPoint-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians’ antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness). DesignObservational cohort simulation study. SettingICU. Participants70 ICU consultants/trainees working in UK-based teaching hospitals. MethodsClinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the ‘improvement’ case), clinico-biological worsening (‘worsening’), clinical improvement/biological worsening (‘discordant clin better’), clinical worsening/biological improvement (‘discordant clin worse’). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence. MeasuresAntibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette. ResultsA negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, 2(1)=25.82, p

ObjectiveThe objective of this study was to explore the outcomes of research engagement (patient engagement, PE) in the context of qualitative research. DesignWe observed engagement in two groups comprised of patients, clinicians and researchers tasked with conducting a qualitative preference exploration project in inflammatory bowel disease. One group was led by a patient research partner (PLG, partner led group) and the other by an academic researcher (RLG, researcher led group). A semistructured guide and a set of critical outcomes of research engagement were used as a framework to ground our analysis. SettingThe study was conducted online. ParticipantsPatient research partners (n=5), researchers (n=5) and clinicians (n=4) participated in this study. Main outcome measuresTranscripts of meetings, descriptive and reflective observation data of engagement during meetings and email correspondence between group members were analysed to identify the outcomes of PE. ResultsBoth projects were patient-centred, collaborative, meaningful, rigorous, adaptable, ethical, legitimate, understandable, feasible, timely and sustainable. Patient research partners (PRPs) in both groups wore dual hats as patients and researchers and influenced project decisions wearing both hats. They took on advisory and operational roles. Collaboration seemed easier in the PLG than in the RLG. The RLG PRPs spent more time than their counterparts in the PLG sharing their experience with biologics and helping their group identify a meaningful project question. A formal literature review informed the design, project materials and analysis in the RLG, while the formal review informed the project materials and analysis in the PLG. A PRP in the RLG and the PLG lead leveraged personal connections to facilitate recruitment. The outcomes of both projects were meaningful to all members of the groups. ConclusionsOur findings show that engagement of PRPs in research has a positive influence on the project design and delivery in the context of qualitative research in both the patient-led and researcher-led group. …

Publication date: Available online 20 November 2023 Source: Infectious Disease Modelling Author(s): Queen Tollett, Salman Safdar, Abba B. Gumel …

Publication date: Available online 20 November 2023 Source: International Journal for Parasitology Author(s): Katie E Crawford, Shannon M Hedtke, Stephen R Doyle, Annette C Kuesel, Samuel Armoo, Mike Y Osei-Atweneboana, Warwick N Grant …

Volume 14, Issue 1, December 2023 .

Tropical Medicine &International Health, EarlyView.

Diverse entomopathogenic fungi, such as the ascomycete Metarhizium, play an essential role in controlling insect populations. About 70 species of Metarhizium have been identified from various host origins, and Metarhizium robertsii was coined as a new species within the Metarhizium anisopliae species complex in 2009. M. robertsii is an ubiquitous soil-dwelling and root-colonizing generalist fungus that can infect, and kill, different orders of insects via cuticle penetration and propagation within insect body cavities.

160 years after the discovery of its waterborne transmission and 120 years after the development of the first-generation of vaccines, typhoid fever remains a major health threat globally. In this Historical Review, we use WHO\'s Institutional Repository for Information Sharing to examine changes in typhoid control policy from January, 1940, to December, 2019. We used a mixed-methods approach in the analysis of infection control priorities, combining semi-inductive thematic coding with historical analysis to show major thematic shifts in typhoid control policy, away from water, sanitation, and hygiene (WASH)-based control towards vaccine-based interventions concurrent with declining attention to the disease.

AbstractBackgroundCritical drug-drug interactions (DDI) and hepatotoxicity complicate concurrent use of rifampicin and protease inhibitors. We investigated whether dose escalation of atazanavir/ritonavir could safely overcome the DDI with rifampicin.MethodsDERIVE (NCT04121195, EDCTP) was a dose-escalation trial in people with HIV on atazanavir/ritonavir-based ART in Uganda. Four intensive pharmacokinetic (PK) visits were performed: PK1 300/100 mg OD (baseline); PK2 300/100 mg OD with rifampicin 600 mg; PK3 300/100 mg BID with rifampicin 600 mg OD; PK4 300/100 mg BID with rifampicin 1200 mg OD. Dolutegravir 50 mg BID throughout the study period ensured participants remained protected from subtherapeutic atazanavir concentrations. The data was interpreted with noncompartmental analysis. The target minimum concentration was atazanavir’s protein-adjusted IC90 (PA-IC90), 0.014 mg/L.ResultsWe enrolled 26 participants (23 female) with median (range) age 44 (28-61) years and weight 67 (50-75) kg. Compared with PK1, atazanavir Ctau, and AUC were significantly reduced at PK2 by 96% and 85%, respectively. The escalation to BID dosing (PK3) reduced this difference in Ctau, and AUC24 to 18% lower and 8% higher, respectively. Comparable exposures were maintained with double doses of rifampicin. Lowest Ctau during PK1, PK3, and PK4 were 12.7-, 4.8-, and 8.6-fold higher than PA-IC90, respectively, while 65% of PK2 Ctau were below the limit of quantification (0.03 mg/L), hence likely below PA-IC90. No participant developed significant elevation of liver enzymes, reported an SAE, or experienced rebound viraemia.ConclusionsTwice daily atazanavir/ritonavir during rifampicin co-administration was well-tolerated and achieved plasma concentrations above the target.

AbstractIntroductionBartonella quintana is a louse-borne bacterium that remains a neglected cause of endocarditis in low-resource settings. Our understanding of risk factors, clinical manifestations and treatment of B. quintana endocarditis are biased by older studies from high-income countries.MethodsWe searched Pubmed Central, Medline, Scopus, Embase, EBSCO (CABI) Global Health, Web of Science and international trial registers for articles published before March 2023 with terms related to Bartonella quintana endocarditis. We included articles containing case-level information on B. quintana endocarditis and extracted data related to patient demographics, clinical features, diagnostic testing, treatment and outcome.ResultsA total of 975 records were identified, of which 569 duplicates were removed prior to screening. 84 articles were eligible for inclusion, describing a total of 167 cases. Infections were acquired in 40 different countries. 62 cases (37.1%) were acquired in low and middle-income countries (LMICs). Disproportionately more female and pediatric patients were from LMICs. More patients presented with heart failure (n = 70/167 [41.9%]) than fever (n = 65/167 [38.9%]). Mean time from symptom onset to presentation was 5.1 months. 25.7% of cases (n = 43/167) were associated with embolization, most commonly to the spleen and brain. 65.5% of antimicrobial regimens included doxycycline. The vast majority of cases underwent valve replacement surgery (n = 154/167, [98.0%]). Overall case fatality rate was 9.6% (n = 16/167).ConclusionB. quintana endocarditis has a global distribution, and long delays between symptom onset and presentation frequently occur. Improved clinician education and diagnostic capacity are needed to screen at-risk populations and identify infection before endocarditis develops.

AbstractBackgroundDrug resistance may be acquired in people starting HIV pre-exposure prophylaxis (PrEP) during undiagnosed infection. Population-based estimates of PrEP-related resistance are lacking.MethodsWe used New York City surveillance and partner services data to measure the effect of PrEP use (tenofovir disoproxil fumarate/tenofivir alafenamide fumarate with emtricitabine) history on baseline prevalence of M184I/V mutations in people diagnosed with HIV, 2015-2022. PrEP use was categorized as “Recent” defined as PrEP stopped ≤ 90 days before diagnosis, “Past” as PrEP stopped >90 days before diagnosis, and “No known use”. Resistance associated mutations were determined using the Stanford Algorithm. We used log binomial regression to generate adjusted relative risk (aRR) of M184I/V by PrEP use history in people with and without acute HIV infection (AHI).ResultsOf 4,246 newly diagnosed people with a genotype ≤30 days of diagnosis, 560 (13%) had AHI, 136 (3%) reported recent, and 124 (35%) past PrEP use; 98 (2%) harbored M184I/V. In people with AHI, recent PrEP use was associated with 6 times greater risk of M184I/V than no known use (aRR: 5.86; 95% confidence interval [CI]: 2.49-13.77). In people without AHI, risk of M184I/V in recent users was 7 times (aRR:7.26; 95% CI: 3.98-13.24), and in past users, 4 times that of people with no known use (aRR: 4.46; 95% CI: 2.15-9.24).ConclusionsPrEP use was strongly associated with baseline M184I/V in NYC, regardless of AHI. Ordering a nucleic acid test when indicated after assessment of exposure, antiretroviral history and AHI symptoms can decrease PrEP initiation in people with undetected infection.

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. …

by Mateus Silva Chang, Isamu Yamamoto This paper estimated the impact of intervention effects (state of emergency (SOE) or quasi-SOE requirements) and information effects (publicized increases in the number of coronavirus disease 2019 (COVID-19) deaths and fear of infection) on preventive behaviors and telecommuting during the COVID-19 pandemic using the Japan Household Panel Survey. Our results indicated that SOEs and quasi-SOEs had positive effects on the adoption of preventive behaviors among individuals, including handwashing, which indicates that an SOE has a direct effect and an indirect effect. Although SOEs in Japan were less enforceable and more lenient than those in other countries, they still had a certain effect on people’s adoption of preventive behaviors. However, the contribution of information effects was much larger than that of intervention effects, suggesting the importance of how and when information should be communicated to the public to prevent the spread of infection.

by Tridip Das, Chandan Nath, Pallabi Das, Keya Ghosh, Tahia Ahmed Logno, Pankqj Debnath, Shuvo Dash, Himadri Shankar Devnath, Shubhagata Das, Md Zohorul Islam The emergence of antimicrobial resistance in commensal bacteria poses a serious public health burden worldwide. Commensals can disseminate the resistance genes to pathogenic bacteria causing life-threatening infections. This cross-sectional study was designed to investigate the antimicrobial resistance pattern and molecular mechanism(s) of ciprofloxacin resistance in commensal E. coli from three major one health components (humans, animals and the environment) in Bangladesh. Samples were randomly collected from broiler chickens, broiler farm environments and hospitalized human patients from the same geographical area. Isolation and identification of E. coli were performed following standard bacteriological techniques. Antimicrobial susceptibility testing (AST) was performed by disk diffusion and broth microdilution methods. Mutation at the quinolone-resistance determining region (QRDR) was analyzed by sequencing. Of 450 samples, a total of 287 (63.8%; 95% CI 59.2–68.1%) E. coli strains was isolated, where 240 (83.6%; 95% CI 78.9–87.5%) strains were phenotypically resistant to ciprofloxacin. The prevalence of ciprofloxacin-resistant E. coli in broiler chicken, broiler farm environments and hospitalized human patients are 77.6%, 88.8% and 89% respectively. In AST against nine antimicrobials, all the isolates were found to be multidrug-resistant (MDR). The minimum inhibitory concentration (MIC) of ciprofloxacin was ranged from 4 to >128mg/L. Point mutations were detected in several sites of QRDR, specifically at 83 and 87 amino acid positions in gyrA gene, and 56, 57, 78, 80 and 84 amino acid positions in parC gene. Mutations resulted in amino acid substitutions. Phylogenetic analysis of gyrA and parC gene sequences showed a close relationship between the strains isolated from different sources. This study demonstrates a high prevalence of ciprofloxacin resistance in commensal E. coli in humans, animals and environment interface and their genealogically similarity poses an alarming public health consequence.

by Ineke Spruijt, Yalda Alam, Huong Nguyen, Bakyt Myrzaliev, Muratbek Ahmatov, Bethrand Odume, Lillian Mtei, Agnes Gebhard, Mustapha Gidado, Degu Jerene Background The measures undertaken to control COVID-19 have disrupted many platforms including tuberculosis (TB) healthcare services. Consequently, declines in TB notifications have been observed in various countries. We visualized changes over time in TB and SARS-CoV-2 infection notifications and reported on country-specific strategies to retain TB care and prevention services in Kyrgyzstan, Nigeria, Tanzania, and Vietnam. Methods We collected and visualized quarterly, retrospective, and country-specific data (Quarter (Q) 1 2018- Q1 2021) on SARS-CoV-2 infection and TB notifications. Additionally, we conducted a country-specific landscape assessment on COVID-19 measures, including lockdowns, operational level strategy of TB care and prevention services, and strategies employed to recover and retain those services. We used negative binomial regression models to assess the association between the installation of COVID-19 measures and changes in TB notifications. Results TB notifications declined in Kyrgyzstan and Vietnam, and (slightly) increased in Nigeria and Tanzania. The changes in TB notifications were associated with the installation of various COVID-19 prevention measures for Kyrgyzstan and Vietnam (declines) and Nigeria (increases). All countries reported reduced TB screening and testing activities. Countries reported the following strategies to retain TB prevention and care services: digital solutions for treatment adherence support, capacity building, and monitor & evaluation activities; adjustment in medication supply/delivery & quantity, including home delivery, pick up points, and month supply; integrated TB/COVID-19 screening & diagnostic platform; and the use of community health care workers. Conclusion Following the COVID-19 pandemic, we did not observe consistent changes in TB notifications across countries. However, all countries reported lower operating levels of TB prevention and care services. Digital health solutions, community-based interventions, and the integration of COVID-19 and TB testing services were employed to recover and retain those services. …

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.

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. …