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Systematic Reviews Mar 2021Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of...
BACKGROUND
Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We summarise the literature on the performance of different rapid tests for exertional desaturation and draw on this evidence base to provide guidance in the context of acute Covid-19.
MAIN RESEARCH QUESTIONS
1. What exercise tests have been used to assess exertional hypoxia at home or in an ambulatory setting in the context of Covid-19 and to what extent have they been validated? 2. What exercise tests have been used to assess exertional hypoxia in other lung conditions, to what extent have they been validated and what is the applicability of these studies to acute Covid-19?
METHOD
AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases were searched to September 2020. Studies where participants had Covid-19 or another lung disease and underwent any form of exercise test which was compared to a reference standard were eligible. Risk of bias was assessed using QUADAS 2. A protocol for the review was published on the Medrxiv database.
RESULTS
Of 47 relevant papers, 15 were empirical studies, of which 11 described an attempt to validate one or more exercise desaturation tests in lung diseases other than Covid-19. In all but one of these, methodological quality was poor or impossible to fully assess. None had been designed as a formal validation study (most used simple tests of correlation). Only one validation study (comparing a 1-min sit-to-stand test [1MSTST] with reference to the 6-min walk test [6MWT] in 107 patients with interstitial lung disease) contained sufficient raw data for us to calculate the sensitivity (88%), specificity (81%) and positive and negative predictive value (79% and 89% respectively) of the 1MSTST. The other 4 empirical studies included two predictive studies on patients with Covid-19, and two on HIV-positive patients with suspected pneumocystis pneumonia. We found no studies on the 40-step walk test (a less demanding test that is widely used in clinical practice to assess Covid-19 patients). Heterogeneity of study design precluded meta-analysis.
DISCUSSION
Exertional desaturation tests have not yet been validated in patients with (or suspected of having) Covid-19. A stronger evidence base exists for the diagnostic accuracy of the 1MSTST in chronic long-term pulmonary disease; the relative intensity of this test may raise safety concerns in remote consultations or unstable patients. The less strenuous 40-step walk test should be urgently evaluated.
Topics: COVID-19; Dyspnea; Exercise; Exercise Test; Humans; Hypoxia; Lung Diseases; Oxygen; Physical Exertion; Predictive Value of Tests; SARS-CoV-2; Sensitivity and Specificity
PubMed: 33726854
DOI: 10.1186/s13643-021-01620-w -
Journal of Fungi (Basel, Switzerland) Feb 2021The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases...
Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.
The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.
PubMed: 33670864
DOI: 10.3390/jof7030176 -
Medical Mycology Jul 2021The epidemiology of Pneumocystis jirovecii, known to colonize the respiratory tract and cause a life-threatening HIV-associated pneumonia (PCP), is poorly described in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The epidemiology of Pneumocystis jirovecii, known to colonize the respiratory tract and cause a life-threatening HIV-associated pneumonia (PCP), is poorly described in Africa. We conducted a systematic review to evaluate P. jirovecii prevalence in African HIV-positive adults with or without respiratory symptoms.
METHODS
We searched Medline, Embase, Cochrane library, Africa-Wide, and Web of Science for studies employing PCR and/or microscopy for P. jirovecii detection in respiratory samples from HIV-positive adults in Africa between 1995 and 2020. Prevalence with respiratory symptoms was pooled using random-effect meta-analysis, and stratified by laboratory method, sample tested, study setting, CD4 count, and trimethoprim/sulfamethoxazole prophylaxis. Colonization prevalence in asymptomatic adults and in adults with non-PCP respiratory disease was described, and quantitative PCR (qPCR) thresholds to distinguish colonization from microscopy-confirmed PCP reviewed.
RESULTS
Thirty-two studies were included, with 27 studies (87%) at high risk of selection bias. P. jirovecii was detected in 19% [95% confidence interval (CI): 12-27%] of 3583 symptomatic and in 9% [95% CI: 0-45%] of 140 asymptomatic adults. Among symptomatic adults, prevalence was 22% [95% CI: 12-35%] by PCR and 15% [95% CI: 9-23%] by microscopy. Seven percent of 435 symptomatic adults had PCR-detected Pneumocystis colonization without evidence of PCP [95% CI: 5-10%, four studies]. One study established a qPCR cutoff of 78 copies/5μl of DNA in 305 induced sputum samples to distinguish Pneumocystis colonization from microscopy-confirmed PCP.
CONCLUSION
Despite widened access to HIV services, P. jirovecii remains common in Africa. Prevalence estimates and qPCR-based definitions of colonization are limited, and overall quality of studies is low.
Topics: Adult; Africa; Asymptomatic Infections; HIV Infections; Humans; Pneumocystis Infections; Pneumocystis carinii; Prevalence
PubMed: 33578417
DOI: 10.1093/mmy/myab002 -
The British Journal of Radiology Feb 2021Chest imaging is often used as a complementary tool in the evaluation of coronavirus disease 2019 (COVID-19) patients, helping physicians to augment their clinical...
Chest imaging is often used as a complementary tool in the evaluation of coronavirus disease 2019 (COVID-19) patients, helping physicians to augment their clinical suspicion. Despite not being diagnostic for COVID-19, chest CT may help clinicians to isolate high suspicion patients with suggestive imaging findings. However, COVID-19 findings on CT are also common to other pulmonary infections and non-infectious diseases, and radiologists and point-of-care physicians should be aware of possible mimickers. This state-of-the-art review goal is to summarize and illustrate possible etiologies that may have a similar pattern on chest CT as COVID-19. The review encompasses both infectious etiologies, such as non-COVID viral pneumonia, , , and pulmonary granulomatous infectious, and non-infectious disorders, such as pulmonary embolism, fat embolism, cryptogenic organizing pneumonia, non-specific interstitial pneumonia, desquamative interstitial pneumonia, and acute and chronic eosinophilic pneumonia.
Topics: Adult; Aged; COVID-19; Community-Acquired Infections; Diagnosis, Differential; Embolism, Fat; Female; Granulomatous Disease, Chronic; Humans; Lung Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Pneumonia, Mycoplasma; Pneumonia, Pneumocystis; Pneumonia, Viral; Pulmonary Embolism; Pulmonary Eosinophilia; Radiography, Thoracic; Time Factors; Tomography, X-Ray Computed
PubMed: 33296607
DOI: 10.1259/bjr.20200703 -
Clinical Microbiology and Infection :... Sep 2020Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-β-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP.
METHOD
We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre- and post-test probability curves.
RESULTS
Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87-94%) and 79% (95%CI 72-84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91-96%) versus 86% (95%CI 78-91%) (p 0.02), with comparable specificity (83%, 95%CI 69-92% versus 83%, 95%CI 72-90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (≤5%) when the pre-test probability was low to intermediate (≤20% in non-HIV and ≤50% in HIV).
CONCLUSIONS
Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.
Topics: Humans; Pneumocystis carinii; Pneumonia, Pneumocystis; Sensitivity and Specificity; Serologic Tests; beta-Glucans
PubMed: 32479781
DOI: 10.1016/j.cmi.2020.05.024 -
Open Forum Infectious Diseases May 2020pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of...
BACKGROUND
pneumonia (PJP) remains a common and highly morbid infection for immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the antimicrobial treatment of choice. However, treatment with TMP-SMX can lead to significant dose-dependent renal and hematologic adverse events. Although TMP-SMX is conventionally dosed at 15-20 mg/kg/d of trimethoprim for the treatment of PJP, reduced doses may be effective and carry an improved safety profile.
METHODS
We conducted a systematic search in the Medline, Embase, and Cochrane Library databases from inception through March 2019 for peer-reviewed studies reporting on reduced doses of TMP-SMX (15 mg/kg/d of trimethoprim or less) for the treatment of PJP. PRISMA, MOOSE, and Cochrane guidelines were followed. Gray literature was excluded.
RESULTS
Ten studies were identified, and 6 were included in the meta-analysis. When comparing standard doses with reduced doses of TMP-SMX, there was no statistically significant difference in mortality (absolute risk difference, -9% in favor of reduced dose; 95% confidence interval [CI], -27% to 8%). When compared with standard doses, reduced doses of TMP-SMX were associated with an 18% (95% CI, -31% to -5%) absolute risk reduction of grade ≥3 adverse events.
CONCLUSIONS
In this systematic review, treatment of PJP with doses of ≤10 mg/kg/d of trimethoprim was associated with similar rates of mortality when compared with standard doses and with significantly fewer treatment-emergent severe adverse events. Although limited by the observational nature of the studies included, this review provides the most current available evidence for the optimal dosing of TMP-SMX in the treatment of PJP.
PubMed: 32391402
DOI: 10.1093/ofid/ofaa112 -
Journal of Infection in Developing... Oct 2018Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an...
INTRODUCTION
Pneumocystis jirovecii (PJ) pneumonia (PJP) is an important opportunistic infection affecting various types of immunocompromised patients and is associated with an increased risk of mortality. PJ is a unique fungal pathogen which is increasingly common and maybe associated with a higher mortality rate in patients without AIDS. We present the characteristics of PJP, diagnosis, and treatment outcomes between AIDS and non-AIDS patients.
METHODOLOGY
We conducted a review of studies of AIDS and non-AIDS patients with PJP using PubMed to search for studies until December 2017.
RESULTS
The annual incidence of AIDS-PJP decreased from 13.4 to 3.3 per 1000 person-years in industrialized countries, while the incidence of non-AIDS-PJP varied widely. Both groups had similar clinical manifestations and radiological features, but the non-AIDS-PJP group potentially had a more fulminant course, more diffuse ground glass opacities, and fewer cystic lesions. The mortality rate decreased in the AIDS-PJP group after the advent of antiretroviral therapy; however, the mortality rate remained high in both groups. A laboratory diagnosis was usually nonspecific; CD4+ T-cell < 200 cells/mL or < 14% favored AIDS-PJP. Serum 1,3-β-D-glucan (BDG) had a high diagnostic odds ratio. Combining BDG and lactic dehydrogenase improved the diagnosis of AIDS-PJP. Histopathological staining and polymerase chain reactions could not discriminate infection from colonization when the result was positive. The use of antibiotics, prophylaxis, and adjunctive corticosteroids was controversial.
CONCLUSIONS
Early diagnosis and treatment can be achieved through vigilance, thereby improving the survival rate for PJP in immunocompromised patients.
Topics: AIDS-Related Opportunistic Infections; Case-Control Studies; Early Diagnosis; Humans; Immunocompromised Host; Pneumocystis carinii; Pneumonia, Pneumocystis; Survival Rate
PubMed: 32004150
DOI: 10.3855/jidc.10357 -
Transplantation Direct Mar 2017Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related pneumonia (HIV-PCP). Guidelines for non-HIV PCP...
BACKGROUND
Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic review and meta-analysis characterizing adjunctive corticosteroids for NH-PCP.
METHODS
We searched MEDLINE from 1966 through 2015. Data on clinical outcomes from NH-PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model.
RESULTS
Our search yielded 5044 abstracts, 277 articles were chosen for full review, and 6 articles described outcomes in moderate to severe NH-PCP. Studies were limited by variable definitions, treatment selection bias, concomitant infections and small sample size. Individual studies reported shorter intensive care unit stay and duration of mechanical ventilation of patients given adjunctive corticosteroids. There was no association between corticosteroids and survival in NH-PCP (odds ratio, 0.66; 95% confidence interval, 0.38-1.15; = 0.14).
CONCLUSIONS
The literature does not support an association between adjunctive corticosteroids and survival from NH-PCP but data are limited and findings should not be considered conclusive. Further research with improved methodology is needed to better understand the role of adjunctive corticosteroids for NH-PCP.
PubMed: 28361121
DOI: 10.1097/TXD.0000000000000642 -
BMC Infectious Diseases Sep 2016Seroprevalence data and clinical studies in children suggest that the burden of pneumocystis pneumonia (PCP) in Africa may be underestimated. We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Seroprevalence data and clinical studies in children suggest that the burden of pneumocystis pneumonia (PCP) in Africa may be underestimated. We performed a systematic review to determine the prevalence and attributable mortality of PCP amongst HIV-infected adults in sub-Saharan Africa.
METHODS
We searched Pubmed, Web of Science, Africa-Wide: NiPAD and CINAHL, from Jan 1 1995 to June 1 2015, for studies that reported the prevalence, mortality or case fatality of PCP in HIV-infected adults living in sub-Saharan African countries. Prevalence data from individual studies were combined by random-effects meta-analysis according to the Mantel-Haenszel method. Data were stratified by clinical setting, diagnostic method, and study year.
RESULTS
We included 48 unique study populations comprising 6884 individuals from 18 countries in sub-Saharan Africa. The pooled prevalence of PCP among 6018 patients from all clinical settings was 15 · 4 % (95 % CI 12 · 9-18 · 0), and was highest amongst inpatients, 22 · 4 % (95 % CI 17 · 2-27 · 7). More cases were identified by bronchoalveolar lavage, 21 · 0 % (15 · 0-27 · 0), compared with expectorated, 7 · 7 % (4 · 4-11 · 1), or induced sputum, 11 · 7 % (4 · 9-18 · 4). Polymerase chain reaction (PCR) was used in 14 studies (n = 1686). There was a trend of decreasing PCP prevalence amongst inpatients over time, from 28 % (21-34) in the 1990s to 9 % (8-10) after 2005. The case fatality rate was 18 · 8 % (11 · 0-26 · 5), and PCP accounted for 6 · 5 % (3 · 7-9 · 3) of study deaths.
CONCLUSIONS
PCP is an important opportunistic infection amongst HIV-infected adults in sub-Saharan Africa, particularly amongst patients admitted to hospital. Although prevalence appears to be decreasing, improved access to antiretroviral therapy and non-invasive diagnostics, such as PCR, are needed.
Topics: AIDS-Related Opportunistic Infections; Africa; Africa South of the Sahara; HIV Infections; Humans; Pneumocystis; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prevalence; Seroepidemiologic Studies; Sputum
PubMed: 27612639
DOI: 10.1186/s12879-016-1809-3 -
Clinical Infectious Diseases : An... Jun 2016To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral... (Meta-Analysis)
Meta-Analysis Review
Incidence of Opportunistic Infections and the Impact of Antiretroviral Therapy Among HIV-Infected Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis.
BACKGROUND
To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in human immunodeficiency virus (HIV)-infected adults in low- and middle-income countries (LMICs).
METHODS
Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random-effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at a CD4 count ≥200 cells/µL were estimated using Joint United Nations Programme on HIV/AIDS (UNAIDS) country estimates and global average OI treatment cost per case.
RESULTS
We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range, 57%-91%) except for tuberculosis, and was largest for oral candidiasis, Pneumocystis pneumonia, and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, $43.8-$49.4 million).
CONCLUSIONS
There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.
Topics: AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Developing Countries; HIV Infections; Humans; Incidence; Tuberculosis
PubMed: 26951573
DOI: 10.1093/cid/ciw125