Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania.

BACKGROUND: The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania. METHODS: In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%). RESULTS: Median age of the 110 participants was 28.5 years (range 17-45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15-46). After a median follow-up of 8.98 months (IQR 5.72-29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6-77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10-2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19-0.82, p = 0.012). CONCLUSION: Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.

Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule.

Background: The Biofire® FilmArray® Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule. Materials: Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests. Results: 1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), Streptococcus pneumoniae (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria. Conclusion: The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Turning radiology reports into epidemiological data to track seasonal pulmonary infections and the COVID-19 pandemic.

OBJECTIVES: To automatically label chest radiographs and chest CTs regarding the detection of pulmonary infection in the report text, to calculate the number needed to image (NNI) and to investigate if these labels correlate with regional epidemiological infection data. MATERIALS AND METHODS: All chest imaging reports performed in the emergency room between 01/2012 and 06/2022 were included (64,046 radiographs; 27,705 CTs). Using a regular expression-based text search algorithm, reports were labeled positive/negative for pulmonary infection if described. Data for regional weekly influenza-like illness (ILI) consultations (10/2013-3/2022), COVID-19 cases, and hospitalization (2/2020-6/2022) were matched with report labels based on calendar date. Positive rate for pulmonary infection detection, NNI, and the correlation with influenza/COVID-19 data were calculated. RESULTS: Between 1/2012 and 2/2020, a 10.8-16.8% per year positive rate for detecting pulmonary infections on chest radiographs was found (NNI 6.0-9.3). A clear and significant seasonal change in mean monthly detection counts (102.3 winter; 61.5 summer; p < .001) correlated moderately with regional ILI consultations (weekly data r = 0.45; p < .001). For 2020-2021, monthly pulmonary infection counts detected by chest CT increased to 64-234 (23.0-26.7% per year positive rate, NNI 3.7-4.3) compared with 14-94 (22.4-26.7% positive rate, NNI 3.7-4.4) for 2012-2019. Regional COVID-19 epidemic waves correlated moderately with the positive pulmonary infection CT curve for 2020-2022 (weekly new cases: r = 0.53; hospitalizations: r = 0.65; p < .001). CONCLUSION: Text mining of radiology reports allows to automatically extract diagnoses. It provides a metric to calculate the number needed to image and to track the trend of diagnoses in real time, i.e., seasonality and epidemic course of pulmonary infections. CLINICAL RELEVANCE: Digitally labeling radiology reports represent previously neglected data and may assist in automated disease tracking, in the assessment of physicians' clinical reasoning for ordering radiology examinations and serve as actionable data for hospital workflow optimization. KEY POINTS: • Radiology reports, commonly not machine readable, can be automatically labeled with the contained diagnoses using a regular-expression based text search algorithm. • Chest radiograph reports positive for pulmonary infection moderately correlated with regional influenza-like illness consultations (weekly data; r = 0.45; p < .001) and chest CT reports with the course of the regional COVID-19 pandemic (new cases: r = 0.53; hospitalizations: r = 0.65; p < 0.001). • Rendering radiology reports into data labels provides a metric for automated disease tracking, the assessment of ordering physicians clinical reasoning and can serve as actionable data for workflow optimization.

Early Target Attainment With Continuous Infusion Meropenem and Piperacillin/Tazobactam and Utilization of Therapeutic Drug Monitoring in Critically Ill Patients: A Retrospective Cohort Study From 2017 to 2020.

Background: We analyzed the attainment of early pharmacological targets of continuous infusion meropenem and piperacillin/tazobactam and the use and effect of a real-time therapeutic drug monitoring (TDM) program on subsequent dosing and target attainment in patients who are critically ill. Methods: This was a single-center, retrospective study among patients hospitalized in the intensive care unit in a Swiss tertiary care hospital from 2017 to 2020. The primary outcome was target attainment [100% tT ≥ 4xECOFF (Pseudomonas aeruginosa)] of continuous infusion meropenem and piperacillin/tazobactam within 72 hours after initiation of treatment. Results: A total of 234 patients were included. Median first meropenem (n = 186 of 234) and piperacillin (n = 48 of 234) concentration was 21 mg/L (interquartile range [IQR], 15.6-28.6) and 100.7 mg/L (IQR, 64.0-160.2), respectively. Pharmacological target was attained in 95.7% (95% confidence interval [CI], 91.7-98.1) of patients receiving meropenem and 77.0% (95% CI, 62.7-87.9) treated with piperacillin/tazobactam. In the univariable and multivariable logistic regression, body weight and estimated glomerular filtration rate were negatively associated with target attainment. Subsequently, meropenem dosage was decreased or stopped in 35 of 186 (18.8%) and 89 of 186 (47.9%) patients, respectively, and increased in 2 of 186 (1.1%) patients. Conclusions: Continuous infusion meropenem and piperacillin/tazobactam yielded excellent and moderate early pharmacological target attainment in critically ill patients, respectively. The TDM was mainly used to decrease meropenem dosage.

Factors impacting the pre-analytical quality of blood cultures-Analysis at a tertiary medical center.

BACKGROUND: Blood cultures (BC) are critical for the diagnosis of bloodstream infections, pathogen identification, and resistance testing. Guidelines recommend a blood volume of 8-10 mL per bottle as lower volumes result in decreased sensitivity. We aimed to evaluate factors for non-adherence to recommended volumes and assess the effects on diagnostic performance. METHODS: From February to April 2020, we measured collected blood volumes by weighing all BC containers from inpatient samples at the University Hospital Basel. Information on BC volumes was merged with clinical and microbiological data, as well as nursing staff schedules. We analyzed factors associated with (i) BC sampling volume, (ii) reaching recommended volumes (≥8 mL), (iii) BC positivity, and (iv) time to positivity using linear and generalized linear mixed effect models. RESULTS: We evaluated a total of 4'118 BC bottles collected from 686 patients. A total of 1'495 (36.3%) of all bottles contained the recommended filling volume of ≥8 mL. Using a central venous and arterial catheter for drawing blood resulted in an increase of filling volume by 0.26 mL (95% CI 0.10, 0.41) and 0.50 mL (95% CI 0.31, 0.69) compared to peripheral venipuncture, respectively. Each additional nursing staff working at the time of blood drawing was associated with 6% higher odds of achieving the recommended filling volume. We found no significant correlation between the filling volume and the positivity rate. CONCLUSION: Our results indicate critical pre-analytical quality markers linked to BC collection procedures to reach recommended collection volumes. No significant impact on the positivity rate was found.

Gout Arthritis During Admission for Decompensated Heart Failure-A Descriptive Analysis of Risk Factors, Treatment and Prognosis.

BACKGROUND: Chronic heart failure and hospital admissions are well-known risk factors for acute gouty arthritis. However, in-depth analyses of patients admitted for decompensated heart failure (DHF) who subsequently developed a gout attack are sparse. This study aims to characterize DHF patients who developed a gout attack during their inpatient treatment and describe potential risk factors, its consequences, and its management in the setting of heart failure exacerbation. METHODS: Retrospective chart review of 50 patients with an admission diagnosis of DHF who subsequently experienced a gout attack during admission at a Swiss tertiary care hospital between 2018 and 2020. Patients with a refusal of the general research consent were excluded (n = 10). RESULTS: A gout attack developed in 66/1,832 (3.6%) DHF admissions of whom 50 individual patients were analyzed. Patients were predominately male (76%), of advanced age (median 80.5 years), with several comorbidities including chronic kidney disease (74%), comorbid gout (70%, only 43% on urate lowering therapy) and hyperuricemia (median 547 µmol/l, IQR 434-667 µmol/l). Diuretics were intensified in all patients. Acute gout presented as polyarticular arthritis (62%) and was often accompanied by fever (30%). Joint aspiration was performed in 32%, and intra-articular steroid injections administered in 20% of patients. Median length of stay and 6-month mortality were 16 days (IQR 12-25) and 32%, respectively, compared to 9 days (IQR 6-14) and 16% for DHF patients without a gout attack. CONCLUSION: Our study highlights features of gout attacks in the context of DHF including the absence of comorbid gout in a significant proportion of patients, the presence of polyarticular disease during the flare, and a poor prognosis. The present study identifies the necessity to better address gout as a comorbidity in DHF patients and may assist clinicians in identifying DHF patients at risk for a gout attack.

Prevalence, incidence and predictors of renal impairment in persons with HIV receiving protease-inhibitors in rural Tanzania.

OBJECTIVE: Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa. METHODS: Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models. RESULTS: Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28-6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03-5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67-0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46-2.78). CONCLUSIONS: In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

Deep learning-based automated detection of pulmonary embolism on CT pulmonary angiograms: No significant effects on report communication times and patient turnaround in the emergency department nine months after technical implementation.

OBJECTIVES: Rapid communication of CT exams positive for pulmonary embolism (PE) is crucial for timely initiation of anticoagulation and patient outcome. It is unknown if deep learning automated detection of PE on CT Pulmonary Angiograms (CTPA) in combination with worklist prioritization and an electronic notification system (ENS) can improve communication times and patient turnaround in the Emergency Department (ED). METHODS: In 01/2019, an ENS allowing direct communication between radiology and ED was installed. Starting in 10/2019, CTPAs were processed by a deep learning (DL)-powered algorithm for detection of PE. CTPAs acquired between 04/2018 and 06/2020 (n = 1808) were analysed. To assess the impact of the ENS and the DL-algorithm, radiology report reading times (RRT), radiology report communication time (RCT), time to anticoagulation (TTA), and patient turnaround times (TAT) in the ED were compared for three consecutive time periods. Performance measures of the algorithm were calculated on a per exam level (sensitivity, specificity, PPV, NPV, F1-score), with written reports and exam review as ground truth. RESULTS: Sensitivity of the algorithm was 79.6 % (95 %CI:70.8-87.2%), specificity 95.0 % (95 %CI:92.0-97.1%), PPV 82.2 % (95 %CI:73.9-88.3), and NPV 94.1 % (95 %CI:91.4-96 %). There was no statistically significant reduction of any of the observed times (RRT, RCT, TTA, TAT). CONCLUSION: DL-assisted detection of PE in CTPAs and ENS-assisted communication of results to referring physicians technically work. However, the mere clinical introduction of these tools, even if they exhibit a good performance, is not sufficient to achieve significant effects on clinical performance measures.

Automated CT Lung Density Analysis of Viral Pneumonia and Healthy Lungs Using Deep Learning-Based Segmentation, Histograms and HU Thresholds.

CT patterns of viral pneumonia are usually only qualitatively described in radiology reports. Artificial intelligence enables automated and reliable segmentation of lungs with chest CT. Based on this, the purpose of this study was to derive meaningful imaging biomarkers reflecting CT patterns of viral pneumonia and assess their potential to discriminate between healthy lungs and lungs with viral pneumonia. This study used non-enhanced and CT pulmonary angiograms (CTPAs) of healthy lungs and viral pneumonia (SARS-CoV-2, influenza A/B) identified by radiology reports and RT-PCR results. After deep learning segmentation of the lungs, histogram-based and threshold-based analyses of lung attenuation were performed and compared. The derived imaging biomarkers were correlated with parameters of clinical and biochemical severity (modified WHO severity scale; c-reactive protein). For non-enhanced CTs (n = 526), all imaging biomarkers significantly differed between healthy lungs and lungs with viral pneumonia (all p < 0.001), a finding that was not reproduced for CTPAs (n = 504). Standard deviation (histogram-derived) and relative high attenuation area [600-0 HU] (HU-thresholding) differed most. The strongest correlation with disease severity was found for absolute high attenuation area [600-0 HU] (r = 0.56, 95% CI = 0.46-0.64). Deep-learning segmentation-based histogram and HU threshold analysis could be deployed in chest CT evaluation for the differentiating of healthy lungs from AP lungs.

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost-benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.

A review of recommendations for infective endocarditis prevention in patients undergoing transcatheter aortic valve implantation.

Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is a new disease entity. The rate of IE after TAVI is similar to that after surgical aortic valve replacement (SAVR), but mortality and prevalence of Enterococcus spp. as causing pathogens are significantly higher. Guidelines on infection prevention measures before TAVI procedures are currently lacking. We performed a structured review of the available data to provide interim recommendations based on guidelines to prevent infections issued by the World Health Organization as well as guidelines by professional societies from Europe and the USA. Such interim recommendations based on expert opinions are probably justified until large randomised trials provide strong evidence for infection control in TAVI, because IE after TAVI is often related to the TAVI procedure itself and the associated mortality rate is high. Antibiotic prophylaxis should be adapted from an intravenous cephalosporin to, e.g., amoxicillin/clavulanic acid, to cover enterococci. In addition, infection control should follow operating room standards as far as is reasonable, even if the evidence for this recommendation is very low. These recommendations are endorsed by the International Society for Cardiovascular Infectious Diseases (ISCVID).

Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.

Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 µg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC50) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.

Extrapulmonary tuberculosis in HIV-infected patients in rural Tanzania: The prospective Kilombero and Ulanga antiretroviral cohort.

BACKGROUND: In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. METHODS: We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. RESULTS: We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/µl (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p <0.001]. CONCLUSIONS: Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.

Repeated Syphilis Episodes in HIV-Infected Men Who Have Sex With Men: A Multicenter Prospective Cohort Study on Risk Factors and the Potential Role of Syphilis Immunity.

BACKGROUND: Syphilis is re-emerging globally in general and HIV-infected populations, and repeated syphilis episodes may play a central role in syphilis transmission among core groups. Besides sexual behavioral factors, little is known about determinants of repeated syphilis episodes in HIV-infected individuals-including the potential impact of preceding syphilis episodes on subsequent syphilis risk. METHODS: In the prospective Swiss HIV cohort study, with routine syphilis testing since 2004, we analyzed HIV-infected men who have sex with men (MSM). Our primary outcome was first and repeated syphilis episodes. We used univariable and multivariable Andersen-Gill models to evaluate risk factors for first and repeated incident syphilis episodes. RESULTS: Within the 14-year observation period, we included 2513 HIV-infected MSM with an initially negative syphilis test. In the univariable and multivariable analysis, the number of prior syphilis episodes (adjusted hazard ratio [aHR] per 1-episode increase, 1.15; 95% confidence interval [CI], 1.01-1.31), having occasional sexual partners with or without condomless anal sex (aHR, 4.99; 95% CI, 4.08-6.11; and aHR, 2.54; 95% CI, 2.10-3.07), and being currently on antiretroviral therapy (aHR, 1.62; 95% CI, 1.21-2.16) were associated with incident syphilis. CONCLUSIONS: In HIV-infected MSM, we observed no indication of decreased syphilis risk with repeated syphilis episodes. The extent of sexual risk behavior over time was the strongest risk factor for repeated syphilis episodes. The observed association of antiretroviral therapy with repeated syphilis episodes warrants further immunological and epidemiological investigation.

Lethal COVID-19: Radiologic-Pathologic Correlation of the Lungs.

PURPOSE: The purpose of this retrospective study was to correlate CT patterns of fatal cases of coronavirus disease 2019 (COVID-19) with postmortem pathology observations. MATERIALS AND METHODS: The study included 70 lung lobes of 14 patients who died of reverse-transcription polymerase chain reaction-confirmed COVID-19. All patients underwent antemortem CT and autopsy between March 9 and April 30, 2020. Board-certified radiologists and pathologists performed lobewise correlations of pulmonary observations. In a consensus reading, 267 radiologic and 257 histopathologic observations of the lungs were recorded and systematically graded according to severity. These observations were matched and evaluated. RESULTS: Predominant CT observations were ground-glass opacities (GGO) (59/70 lobes examined) and areas of consolidation (33/70). The histopathologic observations were consistent with diffuse alveolar damage (70/70) and capillary dilatation and congestion (70/70), often accompanied by microthrombi (27/70), superimposed acute bronchopneumonia (17/70), and leukocytoclastic vasculitis (7/70). Four patients had pulmonary emboli. Bronchial wall thickening at CT histologically corresponded with acute bronchopneumonia. GGOs and consolidations corresponded with mixed histopathologic observations, including capillary dilatation and congestion, interstitial edema, diffuse alveolar damage, and microthrombosis. Vascular alterations were prominent observations at both CT and histopathology. CONCLUSION: A significant proportion of GGO correlated with the pathologic processes of diffuse alveolar damage, capillary dilatation and congestion, and microthrombosis. Our results confirm the presence and underline the importance of vascular alterations as key pathophysiologic drivers in lethal COVID-19.Supplemental material is available for this article.© RSNA, 2020.

Age-related comorbidities and mortality in people living with HIV in rural Tanzania.

OBJECTIVE: Causes of morbidity and mortality of people living with HIV are changing with access to antiretroviral therapy and increased life expectancy. Age-related data on comorbidities and their impact on mortality in sub-Saharan Africa are scarce. DESIGN: This prospective analysis evaluated comorbidities, assessed by means of International Classification of Diseases and Related Health problems 10th revision codes and clinical variables, derived from data collected from the Kilombero & Ulanga antiretroviral cohort of people living with HIV in rural Tanzania. METHODS: We calculated prevalences and incidences of comorbidities in patients enrolled from 2013 to 2017 and evaluated their association with a combined endpoint of death and loss to follow-up (LTFU) in various age groups (15-29, 30-49 and ≥50 years) using Cox regression analysis. RESULTS: Of 1622 patients [65% females, median age 38 years (interquartile range 31-46)], 11% were at least 50 years. During a median follow-up of 22.1 months (interquartile range 10.6-37.3), 48 (2.9%) patients died and 306 (18.9%) were LTFU. Anaemia was the most prevalent comorbidity (66.3%) irrespective of age and was associated with increased mortality/LTFU [hazard ratios 2.02 (95% confidence interval (CI) 1.57-2.60); P < 0.001]. In patients aged at least 50 years, arterial hypertension was highly prevalent (43.8%), but not associated with mortality/LTFU [hazard ratios 1.04 (95% CI 0.56-1.93), P = 0.9]. Undernutrition ranged from 25.5% in the youngest to 29.1% in the oldest age group and contributed to mortality/LTFU [hazard ratios 2.24 (95% CI 1.65-3.04); P < 0.001]. Prevalence of tuberculosis was 21.4% with hazard ratios of 2.54 (95% CI 1.72-3.75, P < 0.001) for mortality/LTFU. CONCLUSION: We show that anaemia, arterial hypertension and undernutrition are the most relevant comorbidities with different age-associated frequencies and impact on death/LTFU in this population.

Prevalence and Evolution of Renal Impairment in People Living With HIV in Rural Tanzania.

BACKGROUND: We assessed the prevalence, incidence, and predictors of renal impairment among people living with HIV (PLWHIV) in rural Tanzania. METHODS: In a cohort of PLWHIV aged ≥15 years enrolled from January 2013 to June 2016, we assessed the association between renal impairment (estimated glomerural filtration rate < 90 mL/min/1.73 m2) at enrollment and during follow-up with demographic and clinical characteristcis using logistic regression and Cox proportional hazards models. RESULTS: Of 1093 PLWHIV, 172 (15.7%) had renal impairment at enrollment. Of 921 patients with normal renal function at baseline, 117 (12.7%) developed renal impairment during a median follow-up (interquartile range) of 6.2 (0.4-14.7) months. The incidence of renal impairment was 110 cases per 1000 person-years (95% confidence interval [CI], 92-132). At enrollment, logistic regression identified older age (adjusted odds ratio [aOR], 1.79; 95% CI, 1.52-2.11), hypertension (aOR, 1.84; 95% CI, 1.08-3.15), CD4 count <200 cells/mm3 (aOR, 1.80; 95% CI, 1.23-2.65), and World Health Organization (WHO) stage III/IV (aOR, 3.00; 95% CI, 1.96-4.58) as risk factors for renal impairment. Cox regression model confirmed older age (adjusted hazard ratio [aHR], 1.85; 95% CI, 1.56-2.20) and CD4 count <200 cells/mm3 (aHR, 2.05; 95% CI, 1.36-3.09) to be associated with the development of renal impairment. CONCLUSIONS: Our study found a low prevalence of renal impairment among PLWHIV despite high usage of tenofovir and its association with age, hypertension, low CD4 count, and advanced WHO stage. These important and reassuring safety data stress the significance of noncommunicable disease surveillance in aging HIV populations in sub-Saharan Africa.

Determinants of antiretroviral adherence among HIV positive children and teenagers in rural Tanzania: a mixed methods study.

BACKGROUND: Around 3.3 million children worldwide are infected with HIV and 90% of them live in sub-Saharan Africa. Our study aimed to estimate adherence levels and find the determinants, facilitators and barriers of ART adherence among children and teenagers in rural Tanzania. METHODS: We applied a sequential explanatory mixed method design targeting children and teenagers aged 2-19 years residing in Ifakara. We conducted a quantitative cross sectional study followed by a qualitative study combining focus group discussions (FGDs) and in-depth interviews (IDIs). We used pill count to measure adherence and defined optimal adherence as > =80% of pills being taken. We analysed determinants of poor adherence using logistic regression. We held eight FGDs with adolescent boys and girls on ART and with caretakers. We further explored issues emerging in the FGDs in four in-depth interviews with patients and health workers. Qualitative data was analysed using thematic content analysis. RESULTS: Out of 116 participants available for quantitative analysis, 70% had optimal adherence levels and the average adherence level was 84%. Living with a non-parent caretaker predicted poor adherence status. From the qualitative component, unfavorable school environment, timing of the morning ART dose, treatment longevity, being unaware of HIV status, non-parental (biological) care, preference for traditional medicine (herbs) and forgetfulness were seen to be barriers for optimal adherence. CONCLUSION: The study has highlighted specific challenges in ART adherence faced by children and teenagers. Having a biological parent as a caretaker remains a key determinant of adherence among children and teenagers. To achieve optimal adherence, strategies targeting the caretakers, the school environment, and the health system need to be designed.