Men's Satisfaction with General Health Services is Associated with Future Use of HIV Testing in Malawi: A Community-Representative Survey.

Across sub-Saharan Africa, men are less likely to know their HIV status than women, leading to later treatment initiation. Little is known about how experiences with general health services affect men's use of HIV testing. We used data from a 2019 community-representative survey of men in Malawi to understand frequency and cause of men's negative health service experiences (defined as men reporting they "would not recommend" a facility) and their association with future HIV testing. We conducted univariable and multivariable logistic regressions to determine which aspects of health facility visits were associated with would-not-recommend experiences and to determine if would-not-recommend experiences 12-24 months prior to the survey were associated with HIV testing in the 12 months prior to the survey. Among 1,098 men eligible for HIV testing in the 12 months prior to the survey, median age was 34 years; 9% of men reported at least one would-not-recommend experience, which did not differ by sociodemographics, gender norm beliefs, or HIV stigma beliefs. The factors most strongly associated with would-not-recommend experiences were cost (aOR 5.8, 95%CI 2.9-11.4), cleanliness (aOR 4.2, 95%CI 1.8-9.9), medicine availability (aOR 3.3, 95%CI 1.7-6.4), and wait times (aOR 2.7, 95%CI 1.5-5.0). Reporting a would-not-recommend experience 12-24 months ago was associated with a 59% decrease in likelihood of testing for HIV in the last 12 months (aOR 0.41; 95% CI:0.17-0.96). Dissatisfaction with general health services was strongly associated with reduced HIV testing. Coverage of high-priority screening services like HIV testing may benefit from improving overall health system quality.

Emergency general surgery in older adult patients: Factors associated with fragmented care.

BACKGROUND: Care fragmentation has been shown to lead to increased morbidity and mortality. We aimed to explore the factors related to care fragmentation after hospital discharge in geriatric emergency general surgery patients, as well as examine the association between care fragmentation and mortality. METHODS: We designed a retrospective study of the Nationwide Readmissions Database 2019. We included patients ≥65 years old admitted with an emergency general surgery diagnosis who were discharged alive from the index admission. The primary outcome was 90-day care fragmentation, defined as an unplanned readmission to a non-index hospital. Multivariable logistic regression was performed, adjusting for patient and hospital characteristics. RESULTS: A total of 447,027 older adult emergency general surgery patients were included; the main diagnostic category was colorectal (22.6%), and 78.2% of patients underwent non-operative management during the index hospitalization. By 90 days post-discharge, 189,622 (24.3%) patients had an unplanned readmission. Of those readmitted, 20.8% had care fragmentation. The median age of patients with care fragmentation was 76 years, and 53.2% were of female sex. Predictors of care fragmentation were living in rural counties (odds ratio 1.76, 95% confidence interval: 1.57-1.97), living in a low-income ZIP Code, discharge to intermediate care facility (odds ratio 1.28, 95% confidence interval: 1.22-1.33), initial non-operative management (odds ratio 1.17, 95% confidence interval: 1.12-1.23), leaving against medical advice (odds ratio 2.60, 95% confidence interval: 2.29-2.96), and discharge from private investor-owned hospitals (odds ratio 1.18, 95% confidence interval: 1.10-1.27). Care fragmentation was significantly associated with higher mortality. CONCLUSION: The burden of unplanned readmissions in older adult patients who survive an emergency general surgery admission is underestimated, and these patients frequently experience care fragmentation. Future directions should prioritize evaluating the impact of initiatives aimed at alleviating the incidence and complications of care fragmentation in geriatric emergency general surgery patients.

Temperature-related increase in growth rate in four freshwater lake fish species.

Growth is one of the most direct and common ways fish respond to climate change, as fish growth is intimately linked to the temperature of the environment. Observational studies on the effect of shifts in temperature on fish growth are scarce for freshwater fish, and particularly lacking for lake populations. Here, changes in growth rate of bream (Abramis brama), perch (Perca fluviatilis), pikeperch (Sander lucioperca), and roach (Rutilus rutilus) over three decades were studied and compared with changes in temperature in the two largest lakes of western Europe: Lake IJsselmeer and Lake Markermeer in the Netherlands. In the autumnal survey catches of bream, perch, and roach, the mean length of YOY increased significantly between 1992 and 2021 in both lakes, but for YOY pikeperch, no temporal changes were found. In a length-stratified dataset of age groups of bream, roach, and perch, the relationship between length and age differed significantly between time periods. In the more recent time periods, indications for higher growth rates across multiple ages were found. Temperature during the growth season increased in the same decades and showed significant correlations with the YOY mean length, for bream, perch, and roach in both lakes, and for pikeperch in Lake Markermeer. These results point toward consistent temperature-induced increases in growth over the age groups for bream, roach, and perch. These increases were found despite the simultaneous process of de-eutrophication in this water system and its potential negative effect on food production. For pikeperch, it is hypothesized that the absence of temporal increase in YOY growth rate is related to its necessary switch to piscivory and subsequent food limitation; the lower thermal range of its main prey smelt, Osmerus eperlanus, is hypothesized to have inhibited food availability for YOY pikeperch and its opportunity to achieve higher growth rates.

A Genomic Urine Assay for Surveillance of Patients with Bladder Cancer Treated with Radiotherapy.

Background: Patients with muscle-invasive bladder cancer (MIBC) who receive radiotherapy with curative intent are followed by imaging, cystoscopy, and urine cytology. However, interpretation of cytology and cystoscopy is hampered by the impact of ionizing radiation on cells. Objective: To assess the diagnostic performance of a genomic urine assay to detect urinary tract recurrences in patients with MIBC treated by (chemo)radiation. Design setting and participants: Patients with nonmetastatic MIBC who underwent (chemo)radiation with curative intent from 2016 to 2020 were prospectively included. Follow-up consisted of cystoscopy and upper tract imaging. Prior to cystoscopy, a urine sample was analyzed to assess mutations in the genes FGFR3, HRAS, and TERT and methylation of OTX1, TWIST1, and ONECUT2. The treating physician was blinded for the assay result. Outcome measurements and statistical analysis: The primary endpoint was a urinary tract recurrence. Cross-sectional sensitivity, specificity, and negative predictive value (NPV) were analyzed using a previously developed logistic regression model for the detection of bladder cancer with this assay. The secondary endpoint was the risk of a future urinary tract recurrence following a positive test and negative cystoscopy/imaging, using a time-dependent Cox proportional hazard analysis. Results and limitations: A total of 143 patients were included, and 503 urine samples were analyzed. The median study duration was 20 mo (interquartile range [IQR] 10-33), and the median time to a recurrence was 16 mo (IQR 12-26). In 27 patients, 32 urinary tract recurrences were diagnosed, including three upper tract tumors. Of 32 recurrences, 18 (56%) had a concomitant urine test available. The diagnostic model had an area under the curve of 0.80 (95% confidence interval [CI] 0.69-0.90) with corresponding sensitivity, specificity, and NPV of 78 (95% CI 52-94), 77% (95% CI 73-81), and 99% (95% CI 97-100). When taking into account the anticipatory effect of the test, 28/32 (88%) recurrences were detected. A Cox regression analysis showed a hazard ratio of 14.8 for the development of a future recurrence (p < 0.001). A major limitation was the lack of a concomitant urine test result in 14/32 (44%) recurrences. Conclusions: A genomic urine assay detected urinary tract recurrences after (chemo)radiation in patients with MIBC, and a positive test was strongly associated with future recurrences. Although validation in a large cohort is warranted, the test has the potential to limit frequent cystoscopies. Patient summary: Radiotherapy is a bladder-sparing treatment in patients with bladder cancer. After treatment, these patients undergo visual inspection of the bladder by cystoscopy to detect possible recurrences. However, interpretation of cystoscopy is difficult due to the effects of radiation on the bladder lining. Hence, we analyzed the diagnostic value of a molecular urine test to detect recurrent disease in bladder cancer patients treated by radiotherapy, and we showed that the urine test has the potential to limit the number of cystoscopies.

Food webs in isolation: The food-web structure of a freshwater reservoir with armoured shores in a former coastal bay area.

Many shallow coastal bays have been closed off from the sea to mitigate the risk of flooding, resulting in coastal reservoir lakes with artificial armoured shorelines. Often these enclosed ecosystems show a persistent decline in biodiversity and ecosystem services, which is likely reflected in their food-web structure. We therefore hypothesize that the food webs of coastal reservoir lakes with armoured shorelines (1) consist of relatively few species with a low food-web connectance and short food chains, and (2) are mainly fuelled by autochthonous organic matter produced in the pelagic zone. To investigate these two hypotheses, we used stable-isotope analysis to determine the food-web structure of lake Markermeer (The Netherlands), a large reservoir lake with armoured shorelines in a former coastal bay area. Contrary to expectation, connectance of the food web in lake Markermeer was comparable to other lakes, while food-chain length was in the higher range. However, the trophic links revealed that numerous macroinvertebrates and fish species in this constructed lake exhibited omnivorous feeding behaviour. Furthermore, in line with our second hypothesis, primary consumers heavily relied on pelagically derived organic matter, while benthic primary production exerted only a minor and seasonal influence on higher trophic levels. Stable-isotope values and the C:N ratio of sediment organic matter in the lake also aligned more closely with phytoplankton than with benthic primary producers. Moreover, terrestrial subsidies of organic matter were virtually absent in lake Markermeer. These findings support the notion that isolation of the lake through shore armouring and the lack of littoral habitats in combination with persistent resuspension of sediments have affected the food web. We argue that restoration initiatives should prioritize the establishment of land-water transition zones, thereby enhancing habitat diversity, benthic primary production, and the inflow of external organic matter while preserving pelagic primary production.

Alignment of molecular subtypes across multiple bladder cancer subtyping classifiers.

BACKGROUND: Treatment of patients with muscle-invasive bladder cancer (MIBC) includes cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). Molecular subtypes have been associated with patient outcomes after NAC and RC, but the reported results have been highly inconsistent. OBJECTIVE: To evaluate the association of molecular subtypes from different classifiers with overall survival (OS) among patients with MIBC who underwent RC. MATERIALS AND METHODS: We analyzed gene expression data generated from transurethral resection of MIBC from a previously assembled and published meta-cohort, NACmeta (N = 601, 247 treated with NAC+RC and 354 RC without NAC), where extended follow-up was available. Molecular subtypes were assigned using the Genomic Subtyping Classifier (GSC), the Consensus Classifier, The Cancer Genome Atlas (TCGA) Classifier, and the Lund Classifier. For survival analysis, inverse probability weighting was used to balance the clinical NAC and non-NAC patient groups. RESULTS: A high consistency in gene expression patterns and nomenclature was observed between luminal-like subtypes, defined as GSC-Luminal, Consensus-Luminal Papillary (LumP), TCGA Luminal-Papillary (LumP) and Lund-UroA, but not for basal-like subtypes such GSC-Basal, Consensus Basal/Squamous, TCGA-Basal/Squamous and Lund-Basal/Squamous. Patients with luminal-like subtypes demonstrated no difference in 3-year OS when treated with or without NAC (P = 0.7 for GSC, P = 0.94 for Consensus, P = 0.87 for TCGA and P = 0.66 for Lund-UroA, respectively). CONCLUSION: Luminal-like molecular subtypes identify a subgroup of MIBC patients who do not appear to benefit from current NAC regimens, even for locally advanced disease. In addition, we were able to illustrate differences in subtyping nomenclature that are not reflected in the underlying biological definition of the subtypes. PATIENT SUMMARY: Muscle-invasive bladder cancer exhibits molecular diversity, and various classifications identify different groups who do not benefit from chemotherapy. On the other hand, there is a high inconsistency in the way cancer groupings are named.

Turning Antibodies into Ratiometric Bioluminescent Sensors for Competition-Based Homogeneous Immunoassays.

Here we present LUCOS (Luminescent Competition Sensor), a modular and broadly applicable bioluminescent diagnostic platform enabling the detection of both small molecules and protein biomarkers. The construction of LUCOS sensors entails the covalent and site-specific coupling of a bioluminescent sensor component to an analyte-specific antibody via protein G-mediated photoconjugation. Target detection is accomplished through intramolecular competition with a tethered analyte competitor for antibody binding. We established two variants of LUCOS: an inherent ratiometric LUCOSR variant and an intensiometric LUCOSI version, which can be used for ratiometric detection upon the addition of a split calibrator luciferase. To demonstrate the versatility of the LUCOS platform, sensors were developed for the detection of the small molecule cortisol and the protein biomarker NT-proBNP. Sensors for both targets displayed analyte-dependent changes in the emission ratio and enabled detection in the micromolar concentration range (KD,app = 16-92 µM). Furthermore, we showed that the response range of the LUCOS sensor can be adjusted by attenuating the affinity of the tethered NT-proBNP competitor, which enabled detection in the nanomolar concentration range (KD,app = 317 ± 26 nM). Overall, the LUCOS platform offers a highly versatile and easy method to convert commercially available monoclonal antibodies into bioluminescent biosensors that provide a homogeneous alternative for the competitive immunoassay.

The Diagnostic Accuracy of Cystoscopy for Detecting Bladder Cancer in Adults Presenting with Haematuria: A Systematic Review from the European Association of Urology Guidelines Office.

CONTEXT: Haematuria can be macroscopic (visible haematuria [VH]) or microscopic (nonvisible haematuria [NVH]), and may be caused by a number of underlying aetiologies. Currently, in case of haematuria, cystoscopy is the standard diagnostic tool to screen the entire bladder for malignancy. OBJECTIVE: The objective of this systematic review is to determine the diagnostic test accuracy of cystoscopy (compared with other tests, eg, computed tomography, urine biomarkers, and urine cytology) for detecting bladder cancer in adults. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for diagnostic test accuracy studies' checklist. The MEDLINE, Embase, Cochrane CENTRAL, and Cochrane CDSR databases (via Ovid) were searched up to July 13, 2022. The population comprises patients presenting with either VH or NVH, without previous urological cancers. Two reviewers independently screened all articles, searched reference lists of retrieved articles, and performed data extraction. The risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). EVIDENCE SYNTHESIS: Overall, nine studies were included in the qualitative analysis. Seven out of nine included trials covered the use of cystoscopy in comparison with radiological imaging. Overall, sensitivity of cystoscopy ranged from 87% to 100%, specificity from 64% to 100%, positive predictive value from 79% to 98%, and negative predictive values between 98% and 100%. Two trials compared enhanced or air cystoscopy versus conventional cystoscopy. Overall sensitivity of conventional white light cystoscopy ranged from 47% to 100% and specificity from 93.4% to 100%. CONCLUSIONS: The true accuracy of cystoscopy for the detection of bladder cancer within the context of haematuria has not been studied extensively, resulting in inconsistent data regarding its performance for patients with haematuria. In comparison with imaging modalities, a few trials have prospectively assessed the diagnostic performance of cystoscopy, confirming very high accuracy for cystoscopy, exceeding the diagnostic value of any other imaging test. PATIENT SUMMARY: Evidence of tests for detecting bladder cancer in adults presenting with haematuria (blood in urine) was reviewed. The most common test used was cystoscopy, which remains the current standard for diagnosing bladder cancer.

Delayed hemothorax readmissions after rib fracture in blunt trauma patients.

Background: Rib fractures are the most common traumatic injury. Hemothorax is one of the widespread complications associated with a rib fracture and occurs in 10-37 % of all rib fractures. Delayed hemothorax (DHTX) is defined as an accumulation of blood within the pleural cavity. Although there is extensive literature on hemothorax, there is limited literature on rib fractures and DHTX readmissions. The objective of this study was to identify potential risk factors for DHTX readmission and examine descriptive information on readmission. Methods: Using the 2016-2019 National Readmission Database (NRD), patients that experienced an admission with a blunt traumatic rib fracture were included. It was determined if the patients experienced DHTX by screening for an admission containing an ICD-10 code for hemothorax within 30 days after an admission containing a ICD-10 code for rib fracture. Univariable and multivariable analysis was performed to determine independent risk factors associated with DHTX readmission. Additionally, information on the clinical and financial characteristics of DHTX readmissions were examined. Results: A total of 242,071 patients were included, of whom 635 experienced DHTX readmission ≤30 days after discharge. Diagnosed with hemothorax on the index admission had the largest odds ratio for DHTX readmission (7.43 [6.14-8.99], P < 0.001). Complications found during DHTX readmission included acute respiratory failure (16.9 %), sepsis (6.9 %), and empyema (4.3 %). Treatment mainly consisted of pleural drainage (62.2 %) and video-assisted thoracoscopic surgery (VATS) evacuation of hemothorax (10.1 %). Conclusion: Patients admitted for a rib fracture have a low incidence for DHTX readmission within 30 days. However, multivariable analysis has demonstrated some risk and protective factors associated with DHTX readmission. Further studies should focus on exploring these risk factors to screen for potential DHTX readmission and/or protective factors to decrease the change for DHTX readmission.

Burnout and depression: A cross sectional study among health care workers providing HIV care during the COVID-19 pandemic in Malawi.

Health care workers (HCWs) in eastern Africa experience high levels of burnout and depression, and this may be exacerbated during the COVID-19 pandemic due to anxiety and increased work pressure. We assessed the prevalence of burnout, depression and associated factors among Malawian HCWs who provided HIV care during the COVID-19 pandemic. From April-May 2021, between the second and third COVID-19 waves in Malawi, we randomly selected HCWs from 32 purposively selected PEPFAR/USAID-supported health facilities for a cross-sectional survey. We screened for depression using the World Health Organization Self Report Questionnaire (positive screen: score≥8) and for burnout using the Maslach Burnout Inventory tool, (positive screen: moderate-high Emotional Exhaustion and/or moderate-high Depersonalization, and/or low-moderate Personal Accomplishment scores). Logistic regression models were used to evaluate factors associated with depression and burnout. We enrolled 435 HCWs, median age 32 years (IQR 28-38), 54% male, 34% were clinical cadres and 66% lay cadres. Of those surveyed, 28% screened positive for depression, 29% for burnout and 13% for both. In analyses that controlled for age, district, and residence (rural/urban), we found that screening positive for depression was associated with expecting to be infected with COVID-19 in the next 12 months (aOR 2.7, 95%CI 1.3-5.5), and previously having a COVID-19 infection (aOR 2.58, 95CI 1.4-5.0). Screening positive for burnout was associated with being in the clinical cadre (aOR 1.86; 95% CI: 1.2-3.0) and having a positive depression screen (aOR 3.2; 95% CI: 1.9-5.4). Reports of symptoms consistent with burnout and depression were common among Malawian HCWs providing HIV care but prevalence was not higher than in surveys before the COVID-19 pandemic. Regular screening for burnout and depression should be encouraged, given the potential for adverse HCW health outcomes and reduced work performance. Feasible interventions for burnout and depression among HCWs in our setting need to be introduced urgently.

A SARS-CoV-2 and influenza rapid antigen test-based hospital isolation policy awaiting RT-PCR, a prospective observational study.

OBJECTIVES: This study aimed to evaluate the clinical performance of a combined SARS-CoV-2/influenza rapid antigen test (SIRAT) and to evaluate a SIRAT-based hospital isolation policy awaiting RT-PCR results for patients presenting at the emergency department (ED). METHODS: We performed a prospective observational study including all adult patients presenting with influenza-like symptoms at the ED of two hospitals from 31 October 2022 to 31 March 2023. A SIRAT and SARS-CoV-2 and influenza RT-PCR were performed on upper respiratory samples. SIRAT results were compared with RT-PCR. Droplet and contact isolation measures (DCIM) were imposed based on SIRAT results awaiting RT-PCR. We monitored symptomatic nosocomial SARS-CoV-2 and influenza infections potentially caused by delayed isolation of patients with false negative SIRAT and the hours of unnecessary DCIM saved. RESULTS: We included 1740 patients of whom 1296 were hospitalized. SARS-CoV-2 and influenza A/B prevalence were 12.7% (221/1740) and 9.9% (171/1740). Sensitivity and specificity of the SIRAT were 67.7% (95% CI 61.1-73.9%) (149/220) and 99.4% (95% CI 99.0-99.8%) (1510/1518) for SARS-CoV-2 and 52.7% (95% CI 44.9-60.4%) (89/169) and 99.1% (95% CI 98.5-99.5%) (1530/1544) for influenza A/B. We found a 0% nosocomial transmission risk for SARS-CoV-2 (95% CI 0-8.8%) and influenza (95% CI 0-10%). In all, 8712 hours in total or a median up to 6 hours 59 minutes (IQR (interquartile range) 11h03) per patient of unnecessary DCIM were saved. DISCUSSION: A SIRAT-guided hospital isolation policy awaiting RT-PCR results for patients who present at the ED can save unnecessary isolation hours without having to lead to significant symptomatic nosocomial transmission of SARS-CoV-2 or influenza viruses.

Provider-led community antiretroviral therapy distribution in Malawi: Retrospective cohort study of retention, viral load suppression and costs.

BACKGROUND: Outcomes of community antiretroviral therapy (ART) distribution (CAD), in which provider-led ART teams deliver integrated HIV services at health posts in communities, have been mixed in sub-Saharan African countries. CAD outcomes and costs relative to facility-based care have not been reported from Malawi. METHODS: We performed a retrospective cohort study in two Malawian districts (Lilongwe and Chikwawa districts), comparing CAD with facility-based ART care. We selected an equal number of clients in CAD and facility-based care who were aged >13 years, had an undetectable viral load (VL) result in the last year and were stable on first-line ART for ≥1 year. We compared retention in care (alive and no period of ≥60 days without ART) using Kaplan-Meier survival analysis and Cox regression and maintenance of VL suppression (<1,000 copies/mL) during follow-up using logistic regression. We also compared costs (in US$) from the health system and client perspectives for the two models of care. Data were collected in October and November 2020. RESULTS: 700 ART clients (350 CAD, 350 facility-based) were included. The median age was 43 years (IQR 36-51), median duration on ART was 7 years (IQR 4-9), and 75% were female. Retention in care did not differ significantly between clients in CAD (89.4% retained) and facility-based care (89.3%), p = 0.95. No significant difference in maintenance of VL suppression were observed between CAD and facility-based care (aOR: 1.24, 95% CI: 0.47-3.20, p = 0.70). CAD resulted in slightly higher health system costs than facility-based care: $118/year vs. $108/year per person accessing care; and $133/year vs. $122/year per person retained in care. CAD decreased individual client costs compared to facility-based care: $3.20/year vs. $11.40/year per person accessing care; and $3.60/year vs. $12.90/year per person retained in care. CONCLUSION: Clients in provider-led CAD care in Malawi had very good retention in care and VL suppression outcomes, similar to clients receiving facility-based care. While health system costs were somewhat higher with CAD, costs for clients were reduced substantially. More research is needed to understand the impact of other differentiated service delivery models on costs for the health system and clients.

Timing of regional analgesia in elderly patients with blunt chest-wall injury.

BACKGROUND: Rib fractures represent a typical injury pattern in older people and are associated with respiratory morbidity and mortality. Regional analgesia modalities are adjuncts for pain management, but the optimal timing for their initiation remains understudied. We hypothesized that early regional analgesia would have similar outcomes to late regional analgesia. METHODS: We retrospectively reviewed the American College of Surgeons Trauma Quality Improvement Program database from 2017 to 2019. We included patients ≥65 years old admitted with blunt chest wall trauma who received regional analgesia. We divided patients into 2 groups: (1) early regional analgesia (within 24 hours of admission) and (2) late regional analgesia (>24 hours). The outcomes evaluated were ventilator-associated pneumonia, mortality, unplanned intensive care unit admission, unplanned intubation, discharge to home, and duration of stay. Univariable analysis and multivariable logistic regression adjusting for patient and injury characteristics, trauma center level, and respiratory interventions were performed. RESULTS: In the study, 2,248 patients were included. The mean (standard deviation) age was 75.3 (6.9), and 52.7% were male. The median injury severity score (interquartile range) was 13 (9-17). The early regional analgesia group had a decreased incidence of unplanned intubation (2.7% vs 5.3%, P = .002), unplanned intensive care unit admission (4.9% vs 8.4%, P < .001), and shorter mean duration of stay (5.5 vs 6.5 days, P = .002). In multivariable analysis, early regional analgesia was associated with decreased odds of unplanned intubation (odds ratio, 0.58; 95% confidence interval, 0.36-0.94; P = .026), unplanned intensive care unit admission (odds ratio, 0.60; 95% confidence interval, 0.041-0.86; P = .006), and increased odds of discharge to home (odds ratio, 1.27; 95% confidence interval, 1.04-1.55; P = .019). After multivariable adjustment, no significant difference was found for ventilator-associated pneumonia or mortality (odds ratio, 0.60; 95% confidence interval, 0.34-1.04; P = .070). CONCLUSION: Early regional analgesia initiation is associated with improved outcomes in older people with blunt chest wall injuries. Geriatric trauma care bundles targeting early initiation of regional analgesia can potentially decrease complications and resource use.

Predictors of Mortality in Extracorporeal Membrane Oxygenation Support Patients Following Major Trauma.

INTRODUCTION: The usage of extracorporeal membrane oxygenation (ECMO) in trauma patients has increased significantly within the past decade. Despite increased research on ECMO application in trauma patients, there remains limited data on factors predicting morbidity and mortality outcome. Therefore, the primary objective of this study is to describe patient characteristics that are independently associated with mortality in ECMO therapy in trauma patients, to further guide future research. METHODS: This retrospective study was conducted using the Trauma Quality Improvement Program database from 2010 to 2019. All adult (age ≥ 16 y) trauma patients that utilized ECMO were included. A Significant differences (P < 0.05) in demographic and clinical characteristics between groups were calculated using an independent t-test for normal distributed continuous values, a Mann-Whitney U test for non-normal distributed values, and a Pearson chi-square test for categorical values. A multivariable regression model was used to identify independent predictors for mortality. A survival flow chart was constructed by using the strongest predictive value for mortality and using the optimal cut-off point calculated by the Youden index. RESULTS: Five hundred forty-two patients were included of whom 205 died. Multivariable analysis demonstrated that the female gender, ECMO within 4 h after presentation, a decreased Glasgow Coma Scale, increased age, units of blood in the first 4 h, and abbreviated injury score for external injuries were independently associated with mortality in ECMO trauma patients. It was found that an external abbreviated injury score of ≥3 had the strongest predictive value for mortality, as patients with this criterion had an overall 29.5% increased risk of death. CONCLUSIONS: There is an ongoing increasing trend in the usage of ECMO in trauma patients. This study has identified multiple factors that are individually associated with mortality. However, more research must be done on the association between mortality and noninjury characteristics like Pao2/Fio2 ratio, acute respiratory distress syndrome classification, etc. that reflect the internal state of the patient.

Multispecies fish tracking across newly created shallow and deep habitats in a forward-restored lake.

BACKGROUND: Freshwater fish communities typically thrive in heterogenous ecosystems that offer various abiotic conditions. However, human impact increasingly leads to loss of this natural heterogeneity and its associated rich fish communities. To reverse this trend, we need guidelines on how to effectively restore or recreate habitats for multiple fish species. Lake Markermeer in the Netherlands is a human-created 70,000-ha lake with a uniform 4 m-water depth, steep shorelines, high wind-induced turbidity, and a declining fish community. In 2016, a forward-looking restoration project newly created a 1000-ha five-island archipelago in this degrading lake, which offered new sheltered shallow waters and deep sand excavations to the fish community. METHODS: In 2020, we assessed how omnivorous and piscivorous fish species used these new habitats by tracking 78 adult fish of five key species across local and lake-scales. We monitored spring arrival of adult fish and assessed local macro-invertebrate and young-of-the-year fish densities. RESULTS: Adult omnivorous Cyprinidae and piscivorous Percidae arrived at the archipelago in early spring, corresponding with expected spawning movements. During the productive summer season, 12 species of young-of-the-year fish appeared along the sheltered shorelines, with particularly high densities of common roach (Rutilus rutilus) and European perch (Perca fluviatilis). This suggests the sheltered, shallow, vegetated waters formed new suitable spawning and recruitment habitat for the fish community. Despite highest food densities for adult fish in the shallowest habitats (< 2-m), adult fish preferred minimally 2-m deep water. After spawning most Cyprinidae left the archipelago and moved long distances through the lake system, while most Percidae remained resident. This may be related to (1) high densities of young-of-the-year fish as food for piscivores, (2) medium food densities for omnivores compared to elsewhere in the lake-system, or (3) the attractiveness of 30-m deep sand excavations that were newly created and frequently used by one-third of all tracked fish. CONCLUSIONS: New littoral zones and a deep sand excavation constructed in a uniform shallow lake that lacked these habitat types attracted omnivorous and piscivorous fish species within four years. Both feeding guilds used the littoral zones for reproduction and nursery, and notably piscivorous fish became residents year-round.

Correlates of uptake of COVID-19 vaccines and motivation to vaccinate among Malawian adults.

COVID-19 vaccine coverage in most countries in Africa remains low. Determinants of uptake need to be better understood to improve vaccination campaigns. Few studies from Africa have identified correlates of COVID-19 vaccination in the general population. We surveyed adults at 32 healthcare facilities across Malawi, purposively sampled to ensure balanced representation of adults with and without HIV. The survey, informed by the World Health Organization's Behavioural and Social Drivers of Vaccination Framework, asked about people's thoughts and feelings about the vaccine, social processes, motivation to vaccinate, and access issues. We classified respondents' COVID-19 vaccination status and willingness to vaccinate, and used multivariable logistic regression to assess correlates of these. Among 837 surveyed individuals (median age was 39 years (IQR 30-49) and 56% were female), 33% were up-to-date on COVID-19 vaccination, 61% were unvaccinated, and 6% were overdue for a second dose. Those up-to-date were more likely to know someone who had died from COVID-19, feel the vaccine is important and safe, and perceive pro-vaccination social norms. Despite prevalent concerns about vaccine side effects, 54% of unvaccinated respondents were willing to vaccinate. Access issues were reported by 28% of unvaccinated but willing respondents. Up-to-date COVID-19 vaccination status was associated with positive attitudes about the vaccine and with perceiving pro-vaccination social norms. Over half of unvaccinated respondents were willing to get vaccinated. Disseminating vaccine safety messages from trusted sources and ensuring local vaccine availability may ultimately increase vaccine uptake.

Visualizing the lymphatic vessels and flow with high-resolution ultrasonography and microvascular flow imaging.

Imaging of the lymphatic system has always encountered difficulties, such as high costs, timeconsuming procedures, and low-resolution images. Each method of imaging provides its own challenges. The use of high-resolution ultrasonography (HR-US) and microvascular flow imaging (MVFI) may prove to be the most effective method for visualizing the superficial lymphatic vessels. This study investigated the utilization of HR-US and MVFI in imaging inguinal lymph nodes and vessels, as well as the innovative use of an intranodal saline injection that acted as a contrast agent. This technical note aims to demonstrate that HR-US and MVFI, in combination with an intranodal saline injection, are applicable to the dynamic imaging of superficial inguinal lymph nodes and vessels.

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

A pseudo-outbreak of MRSA due to laboratory contamination related to MRSA carriage of a laboratory staff member.

BACKGROUND: Methicillin resistant Staphylococcus aureus (MRSA) is a major burden for hospitals globally. However, in the Netherlands, the MRSA prevalence is relatively low due to the 'search and destroy' policy. Routine multiple-locus variable-number of tandem repeat analysis (MLVA) of MRSA isolates supports outbreak detection. However, whole genome multiple locus sequence typing (wgMLST) is superior to MLVA in identifying (pseudo-)outbreaks with MRSA. The present study describes a pseudo-outbreak of MRSA at the bacteriology laboratory of a large Dutch teaching hospital. METHODS: All staff members of the bacteriology laboratory of the Elisabeth-TweeSteden hospital were screened for MRSA carriage, after a laboratory contamination with MRSA was suspected. Clonal relatedness between the index isolate and the MRSA isolates from laboratory staff members and all previous MRSA isolates from the Elisabeth-TweeSteden hospital with the same MLVA-type as the index case was examined based on wgMLST using whole genome sequencing. RESULTS: One of the staff members was identified as the probable source of the laboratory contamination, because of carriage of a MRSA possessing the same MLVA-type as the index case. Eleven other isolates with the same molecular characteristics were found in the database, of which seven were retrospectively suspected of contamination. Clonal relatedness was found between ten isolates, including the isolate found in the staff member and the MRSA found in the index patient with a maximum of eleven alleles difference. All isolates were epidemiologically linked through the laboratory staff member, who had worked on all these cultures. CONCLUSIONS: The present study describes a MRSA pseudo-outbreak over a 2.5-year period due to laboratory contamination caused by a MRSA carrying laboratory staff member involving nine patients. In case of unexpected bacteriological findings, the possibility of a laboratory contamination should be considered.

Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

BACKGROUND: When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response. METHODS: Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson's Chi-squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR). RESULTS: 411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77-86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92-97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48-231]) than participants who experienced ACPR (190 ng/ml [95% CI 101-378], p-value < 0.008). CONCLUSION: Recurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.