Frequency of pleural effusion in dengue patients by severity, age and imaging modality: a systematic review and meta-analysis.

BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.

Is self-rated health associated with cardiovascular risk factors and disease in a low-income setting? A cross-sectional study from the Amazon Basin of Brazil.

OBJECTIVE: Prior studies have suggested that self-rated health may be a useful indicator of cardiovascular disease. Consequently, we aimed to assess the relationship between self-rated health, cardiovascular risk factors and subclinical cardiac disease in the Amazon Basin. DESIGN: Cross-sectional study. SETTING, PARTICIPANTS AND INTERVENTIONS: In participants from the Amazon Basin of Brazil we obtained self-rated health according to a Visual Analogue Scale, ranging from 0 (poor) to 100 (excellent). We performed questionnaires, physical examination and echocardiography. Logistic and linear regression models were applied to assess self-rated health, cardiac risk factors and cardiac disease by echocardiography. Multivariable models were mutually adjusted for other cardiovascular risk factors, clinical and socioeconomic data, and known cardiac disease. OUTCOME MEASURES: Cardiovascular risk factors and subclincial cardiac disease by echocardiography. RESULTS: A total of 574 participants (mean age 41 years, 61% female) provided information on self-rated health (mean 75±21 (IQR 60-90) points). Self-rated health (per 10-point increase) was negatively associated with hypertension (OR 0.87 (95% CI 0.78 to 0.97), p=0.01), hypercholesterolaemia (OR 0.89 (95%CI 0.80 to 0.99), p=0.04) and positively with healthy diet (OR 1.13 (95%CI 1.04 to 1.24), p=0.004). Sex modified these associations (p-interaction <0.05) such that higher self-rated health was associated with healthy diet and physical activity in men, and lower odds of hypertension and hypercholesterolaemia in women. No relationship was found with left ventricular ejection fraction <45% (OR 0.97 (95% CI 0.77 to 1.23), p=0.8), left ventricular hypertrophy (OR 0.97 (95% CI 0.76 to 1.24), p=0.81) or diastolic dysfunction (OR 1.09 (95% CI 0.85 to 1.40), p=0.51). CONCLUSION: Self-rated health was positively associated with health parameters in the Amazon Basin, but not with subclinical cardiac disease by echocardiography. Our findings are of hypothesis generating nature and future studies should aim to determine whether assessment of self-rated health may be useful for screening related to policy-making or lifestyle interventions. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04445103; Post-results.

Prevalence of rheumatic heart disease in adults from the Brazilian Amazon Basin.

BACKGROUND: Rheumatic heart disease (RHD) continues to be a burden in low- and middle-income countries and prevalence estimates are lacking from South America. We aimed to determine the prevalence of RHD in the Brazilian Amazon Basin. METHODS: We examined a random sample of adults (≥18 years) from the general population, who underwent echocardiographic image acquisition by a medical doctor. All images were analyzed according to (i) the 2012 World Heart Federation criteria and (ii) a simplified algorithm for RHD from a previously validated risk score (categories: low-, medium-, high-risk) which involved assessment of the mitral valve (leaflet thickening and excessive motion, regurgitation jet length) and aortic valve (thickening and any regurgitation). RESULTS: A total of 488 adults were screened (mean age 40 ± 15 years, 38% men). The prevalence of RHD was 39/1000 adults (n = 17 definite and n = 2 borderline). Fourteen (74%) had pathological mitral regurgitation, four (21%) mitral stenosis, 0 (0%) pathological aortic regurgitation and six (32%) both mitral and aortic valve disease. None had a prior diagnosis of RHD, 10 (53%) had positive cardiac auscultation and two (11%) reported a history of rheumatic fever. The simplified algorithm identified four (21%) adults as low-risk, six (32%) as intermediate, and nine (47%) as high-risk. CONCLUSIONS: The prevalence of RHD was 39/1000 in adults from the Brazilian Amazon Basin, indicating the need for screening programs in remote areas. A simplified model was only able to categorize every second case of RHD as high-risk. External validation of simplified screening models to increase feasibility in clinical practice are encouraged.

Tropical diseases and risk of hypertension in the Amazon Basin: a cross-sectional study.

Although infectious diseases have been associated with cardiovascular conditions, little is known about tropical disease burden and hypertension. We hypothesized that a history of tropical infections was associated with hypertension. We examined participants from outpatient clinics in the Amazon Basin who were interviewed about prior exposure to tropical diseases, including dengue, malaria hospitalization, and leishmaniasis. Hypertension was defined as a prior physician diagnosis of hypertension, treatment with anti-hypertensive medication, or a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg. We used logistic regression models to examine the relationship between tropical infectious disease and hypertension. We included 556 participants (mean age 41 ± 15 years, 61% women) of whom 214 (38%) had hypertension and 354 (64%) had a history of tropical infectious disease. The distribution of tropical diseases was: dengue 270 (76%), malaria hospitalization 104 (29%) and leishmaniasis 48 (14%). Any prior tropical infection was significantly associated with prevalent hypertension (odds ratio 1.76 [95% CI 1.22-2.54], P = 0.003) and the association remained significant after adjusting for age, sex, body mass index, diabetes, hypercholesterolemia, socioeconomic status, smoking, vegetable intake and serum creatinine. Persons with a history of ≥2 tropical infections (n = 64) had the greatest risk of hypertension (odds ratio 2.04 [95% CI 1.15-3.63], P = 0.015). In adjusted models, prior infection with dengue was associated with hypertension (P = 0.006), but no associations were found with malaria hospitalization (P = 0.39) or leishmaniasis (P = 0.98). In conclusion, a history of tropical infectious disease was associated with hypertension. This finding supports the idea that pathogen burden may be related to cardiovascular conditions.

Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria.

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil. Peripheral blood smears, ECG, and bedside echocardiography were conducted before antimalarial treatment and repeated at follow-up after completed treatment. We evaluated the diagnostic value of PR-segment depression, PR-segment elevation, and Spodick's sign for detecting pericardial effusion. A subset of patients underwent Holter monitoring at baseline. Among 98 cases of uncomplicated malaria (55% men; mean age 40 years; median parasite density 1,774/µl), 75 had Plasmodium vivax, 22 Plasmodium falciparum, and 1 had mixed infection. At baseline, 17% (n = 17) had PR-segment depression, 12% (n = 12) PR-segment elevation, 3% (n = 2) Spodick's sign, and the prevalence of pericardial effusion was 9% (n = 9). ECG alterations had sensitivities of 22% to 89% and specificities of 88% to 100% for detecting pericardial effusion at baseline. PR-segment depression had the best accuracy (sensitivity 89%, specificity 90%). Of the 25 patients, 4 patients who did not have pericardial effusion, displayed nonsustained ventricular tachycardia, determined by Holter monitoring (median duration 43 hours). Follow-up examination data were obtained for 71 patients (median 31 days), for whom PR-segment depression, elevation, and pericardial effusion had reduced significantly (p <0.05). In conclusion, our findings suggest that ECG alterations may be useful to detect pericardial effusion in malaria and that these findings decrease after completed antimalarial treatment.

Reference values for left ventricular dimensions, systolic and diastolic function: a study from the Amazon Basin of Brazil.

Country- and ethnicity-specific reference values for echocardiographic parameters are necessary for decision making. No prior studies have examined reference values in adults from the Amazon Basin of Brazil. We performed echocardiographic examinations in 290 healthy adults (mean age 37 ± 14 years, 40% male) from the Brazilian Amazon. Left ventricular (LV) dimensions and volumes were obtained and indexed to body surface area. We also assessed systolic (LV ejection fraction [LVEF] and global longitudinal strain [GLS]) and diastolic function. LV dimensions and volumes were larger in males compared to females, but after indexation only volumes remained larger (P < 0.001 for all). Parameters of systolic function, were significantly greater in females (LVEF 50 to 68%, GLS - 17 to - 24%) than in males (LVEF 50 to 67%, GLS - 15 to - 23%, P < 0.05). Upper limits of normality for cardiac dimensions (indexed and non-indexed) were markedly higher compared to contemporary guidelines (American Society of Echocardiography) and the Brazilian subgroup in the World Alliance Society of Echocardiography (WASE). Lower limit of normality for LVEF (both sex 50%) and upper limit of normality for the left atrial volume index (LAVI) (male: 31 mL/m2, female: 25 mL/m2) were within normal range but slightly lower compared to guidelines and the WASE study. Other diastolic parameters, including E/A-ratio, E/e' ratio and peak tricuspid regurgitation velocity were compatible with present recommendations. Normal reference ranges of echocardiographic parameters in healthy adults from the Brazilian Amazon Basin may be different compared to international guidelines and data from other regions of Brazil. This applies specifically for LVEF and LAVI.

The prognostic value of myocardial deformational patterns on all-cause mortality is modified by ischemic cardiomyopathy in patients with heart failure.

Early systolic lengthening and postsystolic shortening may yield prognostic information in cardiovascular high-risk groups. We aimed to investigate the prognostic potential of these patterns in patients with heart failure with reduced ejection fraction (HFrEF), and specifically if the value was greater in patients with ischemic etiology. A total of 884 patients with HFrEF (66 ± 12 years, male 73%, mean EF 28 ± 9%) underwent speckle tracking echocardiography. Of these, 61% suffered from ischemic cardiomyopathy (ICM). Patients were followed for all-cause mortality. We assessed myocardial lengthening during early systole, defined by the early systolic strain index (ESI): [-100x (peak positive strain/maximal strain)] and myocardial shortening after aortic valve closure, defined by the postsystolic strain index (PSI): [100x (postsystolic strain-peak systolic strain)/maximal strain]. During median follow-up of 3.4 [interquartile range 1.9 to 4.8] years, 132 patients (15%) died. ICM modified the relationship between ESI and all-cause mortality (P interaction = 0.008), but not for PSI (P interaction = 0.13). When assessing patients with ICM by Cox proportional hazards models, per 1% increase in ESI (HR 1.09 [1.04 to 1.15], P < 0.001) and PSI (HR 1.02 [1.01 to 1.03], P = 0.002) were associated with all-cause mortality. However, in multivariable models adjusted for clinical, invasive and echocardiographic information, only ESI was a predictor of the endpoint (HR 1.07 [1.00 to 1.13], P = 0.023). In patients with no ICM, neither ESI (HR 0.99 per 1% increase [0.90 to 1.09], P = 0.86) nor PSI (HR 1.00 per 1% increase [0.99 to 1.02], P = 0.88) were associated with all-cause mortality. Our results indicate that in HFrEF patients with ischemic etiology, the ESI may provide some information on prognosis, whereas the prognostic value of PSI is reduced. In patients with HFrEF and no prior exposure to ischemia, the prognostic value of both deformational patterns is reduced.

Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients.

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1-91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

Prevalence of Cardiovascular Complications in Malaria: A Systematic Review and Meta-Analysis.

Recent studies have suggested that malaria may affect the cardiovascular system. The aim of this systematic review and meta-analysis was to determine the prevalence of cardiovascular complications in symptomatic malaria patients. We searched databases such as Pubmed, Embase, Cochrane, and Web of Science (January 1950-April 2020) for studies reporting on cardiovascular complications in adults and children with malaria. Cardiovascular complications were defined as abnormalities in electrocardiogram (ECG), cardiac biomarkers, and echocardiography on admission or during outpatient examination. Studies of patients with known heart disease or cardiovascular evaluation performed after the start of intravenous antimalarial medication were excluded. The study was registered in International Prospective Register of Systematic Reviews (PROSPERO) (No.: CRD42020167672). The literature search yielded 1,243 studies, and a total of 43 studies with symptomatic malaria patients were included. Clinical studies (n = 12 adults; n = 5 children) comprised 3,117 patients, of which a majority had Plasmodium falciparum (n = 15) and were diagnosed with severe malaria (n = 13). In random-effects models of adults, the pooled prevalence estimate for any cardiovascular complication was 7% (95% CI: 5-9). No meta-analysis was conducted in children, but the range of abnormal ECG was 0-8%, cardiac biomarkers 0-57%, and echocardiography 4-9%. We analyzed 33 cases (n = 10 postmortem), in which the most common cardiovascular pathologies were myocarditis and acute coronary syndrome. All histopathological studies found evidence of parasitized red blood cells in the myocardium. Cardiovascular complications are not uncommon in symptomatic adults and children with malaria. Additional studies investigating malaria and cardiovascular disease are encouraged.

Short- vs. Long-Course Antibiotic Treatment for Acute Streptococcal Pharyngitis: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: To evaluate the effectiveness of short courses of antibiotic therapy for patients with acute streptococcal pharyngitis. METHODS: Randomized controlled trials comparing short-course antibiotic therapy (≤5 days) with long-course antibiotic therapy (≥7 days) for patients with streptococcal pharyngitis were included. Two primary outcomes: early clinical cure and early bacterial eradication. RESULTS: Fifty randomized clinical trials were included. Overall, short-course antibiotic treatment was as effective as long-course antibiotic treatment for early clinical cure (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.79 to 1.15). Subgroup analysis showed that short-course penicillin was less effective for early clinical cure (OR 0.43; 95% CI, 0.23 to 0.82) and bacteriological eradication (OR 0.34; 95% CI, 0.19 to 0.61) in comparison to long-course penicillin. Short-course macrolides were equally effective, compared to long-course penicillin. Finally, short-course cephalosporin was more effective for early clinical cure (OR 1.48; 95% CI, 1.11 to 1.96) and early microbiological cure (OR 1.60; 95% CI, 1.13 to 2.27) in comparison to long-course penicillin. In total, 1211 (17.7%) participants assigned to short-course antibiotic therapy, and 893 (12.3%) cases assigned to long-course, developed adverse events (OR 1.35; 95% CI, 1.08 to 1.68). CONCLUSIONS: Macrolides and cephalosporins belong to the list of "Highest Priority Critically Important Antimicrobials"; hence, long-course penicillin V should remain as the first line antibiotic for the management of patients with streptococcal pharyngitis as far as the benefits of using these two types of antibiotics do not outweigh the harms of their unnecessary use.

Early Systolic Lengthening in Patients With ST-Segment-Elevation Myocardial Infarction: A Novel Predictor of Cardiovascular Events.

Background Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force. We sought to evaluate the prognostic potential of ESL in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results We prospectively enrolled 373 patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. All patients underwent a speckle tracking echocardiographic examination a median of 2 days (interquartile range, 1-3 days) after the percutaneous coronary intervention. We assessed a novel viability index, the ESL index, defined as follows: [-100×(peak positive systolic strain/peak negative strain in cardiac cycle)]. We also calculated ESL duration, defined as time from onset of QRS complex on the ECG to time of peak positive systolic strain. Both parameters were averaged from 18 myocardial segments. During a median follow-up of 5.3 years (interquartile range, 2.5-6.0 years), 145 (39%) experienced major adverse cardiovascular events, a composite of incident heart failure, new myocardial infarction, and all-cause mortality. The ESL index and ESL duration were significantly increased in culprit lesion areas (6.7±6.2% versus 5.0±4.1% and 43±33 ms versus 33±24 ms, respectively; P<0.001 for both). In Cox proportional hazard models, the ESL index (hazard ratio, 1.27 per 1% increase; 95% CI, 1.13-1.43; P<0.001) and ESL duration (hazard ratio, 1.49 per 1-ms increase; 95% CI, 1.15-1.92; P=0.002) yielded prognostic information on major adverse cardiovascular events. Both associations remained significant after adjusting for clinical, echocardiographic, and invasive confounders. Conclusions Assessment of ESL after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction yields independent and significant prognostic information on the future risk of cardiovascular events.