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The Journal of Allergy and Clinical... Oct 2023Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased...
BACKGROUND
Antibiotics are the first-line treatment for bacterial infections; however, overuse and inappropriate prescribing have made antibiotics less effective with increased antimicrobial resistance. Unconfirmed reported antibiotic allergy labels create a significant barrier to optimal antimicrobial stewardship in health care, with clinical and economic implications.
OBJECTIVE
A systematic review was conducted to summarize the impact of patient-reported antibiotic allergy on clinical outcomes and various strategies that have been employed to effectively assess and remove these allergy labels, improving patient care.
METHODS
The review was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A critical appraisal was conducted on all studies and a narrative synthesis was performed to identify themes.
RESULTS
Four themes emerged: the prevalence of antibiotic allergy, impact of antibiotic allergy on antimicrobial prescribing, impact of antibiotic allergy on clinical outcomes, and delabeling strategies to improve clinical outcomes. Of the 32 studies, including 1,089,675 participants, the prevalence of reported antibiotic allergy was between 5% and 35%. Patients with a reported antibiotic allergy had poorer concordance with prescribing guidelines in 30% to 60% of cases, with a higher use of alternatives such as quinolone, tetracycline, macrolide, lincosamide, and carbapenem and lower use of beta-lactam antibiotics. Antibiotic allergy delabeling was identified as an intervention and recommendation to advance the state of the science.
CONCLUSIONS
There is substantial evidence within the literature that antibiotic allergy labels significantly impact patient clinical outcomes and a consensus that systematic assessment of reported antibiotic allergies, commonly referred to as delabeling, improves the clinical management of patients.
Topics: Humans; Self Report; Anti-Bacterial Agents; Drug Hypersensitivity; Delivery of Health Care; Hypersensitivity; Penicillins
PubMed: 37352931
DOI: 10.1016/j.jaip.2023.06.025 -
Rheumatology (Oxford, England) Dec 2023To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.
OBJECTIVE
To evaluate the evidence concerning systemic pharmacological treatments for SSc digital ulcers (DUs) to inform the development of evidence-based treatment guidelines.
METHODS
A systematic literature review of seven databases was performed to identify all original research studies of adult patients with SSc DUs. Randomized controlled trials (RCTs) and prospective longitudinal observational studies (OBSs) were eligible for inclusion. Data were extracted, applying the patient, intervention, comparison, outcome framework, and risk of bias (RoB) was assessed. Due to study heterogeneity, narrative summaries were used to present data.
RESULTS
Forty-seven studies that evaluated the treatment efficacy or safety of pharmacological therapies were identified among 4250 references. Data from 18 RCTs of 1927 patients and 29 OBSs of 661 patients, at various RoB (total 2588 patients) showed that i.v. iloprost, phosphodiesterase-5 inhibitors and atorvastatin are effective for the treatment of active DUs. Bosentan reduced the rate of future DUs in two RCTs (moderate RoB) and eight OBSs at low to high RoB. Two small studies (moderate RoB) indicate that Janus kinase inhibitors may be effective for the treatment of active DUs, otherwise there are no data to support the use of immunosuppression or anti-platelet agents in the management of DUs.
CONCLUSION
There are several systemic treatments, across four medication classes, that are effective therapies for the management of SSc DUs. However, a lack of robust data means it is not possible to define the optimal treatment regimen for SSc DUs. The relatively low quality of evidence available has highlighted further areas of research need.
Topics: Adult; Humans; Skin Ulcer; Fingers; Scleroderma, Systemic; Bosentan
PubMed: 37335850
DOI: 10.1093/rheumatology/kead289 -
The Lancet. HIV Jun 2023Poverty and social inequality are risk factors for poor health outcomes in patients with HIV/AIDS. In addition to eligibility, cash transfer programmes can be divided... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poverty and social inequality are risk factors for poor health outcomes in patients with HIV/AIDS. In addition to eligibility, cash transfer programmes can be divided into two categories: those with specific requirements (conditional cash transfers [CCTs]) and those without specific requirements (unconditional cash transfers). Common CCT requirements include health care (eg, undergoing an HIV test) and education (eg, children attending school). Trials assessing the effect of cash transfer programmes on HIV/AIDS outcomes have yielded divergent findings. This review aimed to summarise evidence to evaluate the effects of cash transfer programmes on HIV/AIDS prevention and care outcomes.
METHODS
For this systematic review and meta-analysis, we searched PubMed, EMBASE, Cochrane Library, LILACS, WHO IRIS, PAHO-IRIS, BDENF, Secretaria Estadual de Saúde SP, Localizador de Informação em Saúde, Coleciona SUS, BINACIS, IBECS, CUMED, SciELO, and Web of Science up to Nov 28, 2022. We included randomised controlled trials (RCTs) that evaluated the effects of cash transfer programmes on HIV incidence, HIV testing, retention in HIV care, and antiretroviral therapy adherence, and conducted risk of bias and quality of evidence assessments using the Cochrane Risk of Bias tool and the Grading of Recommendations, Assessment, Development, and Evaluations approach. A random-effects meta-analysis model was used to combine studies and calculate risk ratios (RRs). Subgroup analyses were performed using conditionality types (ie, school attendance or health care). The protocol was registered with PROSPERO, CRD42021274452.
FINDINGS
16 RCTs, which included 5241 individuals, fulfilled the inclusion criteria. Of these, 13 studies included conditionalities for receiving cash transfer programmes. The results showed that receiving a cash transfer was associated with lowered HIV incidence among individuals who had to meet health-care conditionalities (RR 0·74, 95% CI 0·56-0·98) and with increased retention in HIV care for pregnant women (1·14, 95% CI 1·03-1·27). No significant effect was observed for HIV testing (RR 0·45, 95% CI 0·18-1·12) or antiretroviral therapy adherence (1·13, 0·73-1·75). Lower risk of bias was observed for HIV incidence and having an HIV test. The strength of available evidence can be classified as moderate.
INTERPRETATION
Cash transfer programmes have a positive effect on mitigating HIV incidence for individuals who have to meet health-care conditionalities and on increasing retention in HIV care for pregnant women. These results show the potential of cash transfer programmes for HIV prevention and care, especially among people in extreme poverty, and highlight that cash transfer programmes must be considered when developing policies for HIV/AIDS control, as indicated by the UNAIDS 95-95-95 target of the HIV care continuum.
FUNDING
National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.
Topics: United States; Pregnancy; Child; Female; Humans; Acquired Immunodeficiency Syndrome; HIV Infections; Socioeconomic Factors; Risk Factors; Poverty
PubMed: 37270225
DOI: 10.1016/S2352-3018(22)00290-9 -
The Cochrane Database of Systematic... May 2023Asparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asparaginase has played a crucial role in the improvement of survival in children with acute lymphoblastic leukaemia (ALL), which is the commonest cancer among children. Survival rates have steadily increased over decades since the introduction of asparaginase to ALL therapy, and overall survival rates reach 90% with the best contemporary protocols. Currently, polyethylene glycolated native Escherichia coli-derived L-asparaginase (PEG-asparaginase) is the preferred first-line asparaginase preparation. Besides its clinical benefits, PEG-asparaginase is well known for severe toxicities. Agreement on the optimal dose, treatment duration, and frequency of administration has never been reached among clinicians.
OBJECTIVES
Primary objective To assess the effect of the number of PEG-asparaginase doses on survival and relapse in children and adolescents with ALL. Secondary objectives To assess the association between the number of doses of PEG-asparaginase and asparaginase-associated toxicities (e.g. hypersensitivity, thromboembolism, pancreatitis and osteonecrosis). To undertake a network meta-analysis at dose-level in order to generate rankings of the number of doses of PEG-asparaginase used in the treatment for ALL, according to their benefits (survival and relapse) and harms (toxicity).
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, Web of Science databases and three trials registers in November 2021, together with reference checking, citation searching and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing different PEG-asparaginase treatment regimens in children and adolescents (< 18 years of age) with first-line ALL treated with multiagent chemotherapy including PEG-asparaginase.
DATA COLLECTION AND ANALYSIS
Using a standardised data collection form, two review authors independently screened and selected studies, extracted data, assessed risk of bias for each outcome using a standardised tool (RoB 2.0) and assessed the certainty of evidence for each outcome using the GRADE approach. Primary outcomes included overall survival, event-free survival and leukaemic relapse. Secondary outcomes included asparaginase-associated toxicities (hypersensitivity, thromboembolism, pancreatitis, sinusoidal obstruction syndrome and osteonecrosis as well as overall asparaginase-associated toxicity). We conducted the review and performed the analyses in accordance with the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included three RCTs in the review, and identified an additional four ongoing studies. We judged outcomes of two RCTs to be at low risk of bias in all the Cochrane risk of bias (RoB 2) domains. We rated the remaining study as having some concerns regarding bias. Due to concerns about imprecision, we rated all outcomes as having low- to moderate-certainty evidence. One study compared intermittent PEG-asparaginase treatment (eight doses of PEG-asparaginase, 1000 IU/m, intramuscular (IM) administration) versus continuous PEG-asparaginase treatment (15 doses of PEG-asparaginase, 1000 IU/m, IM) in 625 participants with non-high risk ALL aged 1.0 to 17.9 years. We found that treatment with eight doses probably results in little to no difference in event-free survival compared to treatment with 15 doses (RR 1.01, 95% CI 0.97 to 1.06; moderate-certainty evidence). Compared to treatment with 15 doses, treatment with eight doses may result in either no difference or a slight reduction in hypersensitivity (RR 0.64, 95% CI 0.21 to 1.93; low-certainty evidence), thromboembolism (RR 0.55, 95% CI 0.22 to 1.36; low-certainty evidence) or osteonecrosis (RR 0.68, 95% CI 0.35 to 1.32; low-certainty evidence). Furthermore, we found that treatment with eight doses probably reduces pancreatitis (RR 0.31, 95% CI 0.12 to 0.75; moderate-certainty evidence) and asparaginase-associated toxicity (RR 0.53, 95% CI 0.35 to 0.78; moderate-certainty evidence) compared to treatment with 15 doses. One study compared low-risk standard treatment with additional PEG-asparaginase (six doses, 2500 IU/m, IM) versus low-risk standard treatment (two doses, 2500 IU/m, IM) in 1857 participants aged one to nine years old with standard low-risk ALL. We found that, compared to treatment with two doses, treatment with six doses probably results in little to no difference in overall survival (RR 0.99, 95% CI 0.98 to 1.00; moderate-certainty evidence) and event-free survival (RR 1.01, 95% CI 0.99 to 1.04; moderate-certainty evidence), and may result in either no difference or a slight increase in osteonecrosis (RR 1.65, 95% CI 0.91 to 3.00; low-certainty evidence). Furthermore, we found that treatment with six doses probably increases hypersensitivity (RR 12.05, 95% CI 5.27 to 27.58; moderate-certainty evidence), pancreatitis (RR 4.84, 95% CI 2.15 to 10.85; moderate-certainty evidence) and asparaginase-associated toxicity (RR 4.49, 95% CI 3.05 to 6.59; moderate-certainty evidence) compared to treatment with two doses. One trial compared calaspargase (11 doses, 2500 IU/m, intravenous (IV)) versus PEG-asparaginase (16 doses, 2500 IU/m, IV) in 239 participants aged one to 21 years with standard- and high-risk ALL and lymphoblastic lymphoma. We found that treatment with 11 doses of calaspargase probably results in little to no difference in event-free survival compared to treatment with 16 doses of PEG-asparaginase (RR 1.06, 95% CI 0.97 to 1.16; moderate-certainty evidence). However, treatment with 11 doses of calaspargase probably reduces leukaemic relapse compared to treatment with 16 doses of PEG-asparaginase (RR 0.32, 95% CI 0.12 to 0.83; moderate-certainty evidence). Furthermore, we found that treatment with 11 doses of calaspargase results in either no difference or a slight reduction in hypersensitivity (RR 1.17, 95% CI 0.64 to 2.13; low-certainty evidence), pancreatitis (RR 0.85, 95% CI 0.47 to 1.52; low-certainty evidence), thromboembolism (RR 0.83, 95% CI 0.48 to 1.42; low-certainty evidence), osteonecrosis (RR 0.63, 95% CI 0.15 to 2.56; low-certainty evidence) and asparaginase-associated toxicity (RR 1.00, 95% CI 0.71 to 1.40; low-certainty evidence) compared to treatment with 16 doses of PEG-asparaginase.
AUTHORS' CONCLUSIONS
We were not able to conduct a network meta-analysis, and could not draw clear conclusions because it was not possible to rank the interventions. Overall, we found that different numbers of doses of PEG-asparaginase probably result in little to no difference in event-free survival across all studies. In two studies, we found that a higher number of PEG-asparaginase doses probably increases pancreatitis and asparaginase-associated toxicities.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Asparaginase; Neoplasm Recurrence, Local; Network Meta-Analysis; Pancreatitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Systematic Reviews as Topic; Thromboembolism; Recurrence
PubMed: 37260073
DOI: 10.1002/14651858.CD014570.pub2 -
Journal of Cutaneous Medicine and... 2023Human herpesvirus-6 (HHV-6) is a ubiquitous lymphotropic betaherpesvirus that can reactivate in drug rash with eosinophilia and systemic symptoms (DRESS). Despite recent... (Review)
Review
INTRODUCTION
Human herpesvirus-6 (HHV-6) is a ubiquitous lymphotropic betaherpesvirus that can reactivate in drug rash with eosinophilia and systemic symptoms (DRESS). Despite recent publications advancing our understanding of HHV-6 in DRESS, the exact role of HHV-6 in disease pathogenesis remains unclear.
METHODS
A scoping review with the PubMed query "(HHV 6 AND (drug OR DRESS OR DIHS)) OR (HHV6 AND (drug OR DRESS OR DIHS))" was conducted in accordance with PRISMA guidelines. Articles containing original data on at least one DRESS patient with HHV-6 testing were included.
RESULTS
Our search returned a total of 373 publications, of which 89 met eligibility criteria. HHV-6 reactivation occurred in 63% of DRESS patients (n = 748), which was significantly more often than other herpesviruses. HHV-6 reactivation was associated with worse outcomes and greater severity in controlled studies. Case reports have demonstrated sometimes fatal HHV-6-related multi-organ involvement. Temporally, HHV-6 reactivation typically occurs 2 to 4 weeks after DRESS onset and has been linked to markers of immunologic signaling, such as OX40 (CD134), an HHV-6 entry receptor. Efficacy of antiviral or immunoglobulin treatment has only been demonstrated anecdotally, and steroid use may affect HHV-6 reactivation.
CONCLUSION
HHV-6 is implicated in DRESS more than in any other dermatologic condition. It is still unclear whether HHV-6 reactivation is cause or consequence of DRESS dysregulation. Similar pathogenic mechanisms precipitated by HHV-6 in other contexts may be relevant in DRESS. Future randomized controlled studies to assess effects of viral suppression on clinical outcomes is needed.
Topics: Humans; Herpesvirus 6, Human; Eosinophilia; Drug Eruptions; Exanthema
PubMed: 37231539
DOI: 10.1177/12034754231177590 -
The Lancet. Global Health Jun 2023Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests.
METHODS
In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337.
FINDINGS
We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies.
INTERPRETATION
AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples.
FUNDING
FIND, the Global Alliance for Diagnostics.
Topics: Humans; Male; Female; Sputum; Bayes Theorem; Cross-Sectional Studies; Tuberculosis; Lipopolysaccharides; HIV Infections; Sensitivity and Specificity; Mycobacterium tuberculosis
PubMed: 37202025
DOI: 10.1016/S2214-109X(23)00135-3 -
European Journal of Radiology Jul 2023Covid-19 related lockdowns have resulted in a shortage of iodinated contrast media (ICM) in 2022. Health care providers have reacted with implementing conservation... (Review)
Review
PURPOSE
Covid-19 related lockdowns have resulted in a shortage of iodinated contrast media (ICM) in 2022. Health care providers have reacted with implementing conservation strategies to stay operational without compromising patient care. Although articles describing the implemented Interventions have been published, possible chances of the shortage have not yet been mentioned in the literature.
METHODS
We conducted a literature search in PubMed and Google Scholar, and analysed the background, interventions, and possible benefits of low-dose ICM regimens.
RESULTS
We included 22 articles dealing with "ICM shortage" for the analysis. The delivery bottlenecks in the USA and Australia led to two different countermeasures, 1. reduction of the number of contrast-enhanced image-guided examinations and 2. reduction of the (single) ICM dose. Interventions from both groups have resulted in significant reduction of ICM usage; however, group 1 has contributed more to overall ICM reduction. As benefit of the ICM reduction, we revealed an increased safety for patients at risk (e.g. hypersensitivity reactions, contrast-induced acute kidney injury, thyroid toxic effects).
CONCLUSION
The ICM shortage of 2022 has forced health care providers to implement conservation strategies to stay operational. Although there were already proposals for dose reduction before the corona pandemic and the associated supply bottlenecks, this situation led to the use of a reduced amount of contrast agent on a large scale. This presents a good opportunity to reconsider protocols and the use of contrast-enhanced imaging in general for future practice as it offers chances and advantages regarding costs, environmental impact, and patient safety.
Topics: Humans; Contrast Media; COVID-19; Communicable Disease Control; Iodine Compounds; Drug-Related Side Effects and Adverse Reactions
PubMed: 37156181
DOI: 10.1016/j.ejrad.2023.110853 -
The Lancet. HIV May 2023Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised...
BACKGROUND
Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised (standard-of-care, SOC) testing, but can be more expensive. We evaluated cost-effectiveness data from mathematical models comparing POC with SOC to provide global policy guidance.
METHODS
In this systematic review of modelling studies, we searched PubMed, MEDLINE, Embase, the National Health Service Economic Evaluation Database, Econlit, and conference abstracts, combining terms for "HIV" + "infant"/"early infant diagnosis" + "point-of-care" + "cost-effectiveness" + "mathematical models", without restrictions from database inception to July 15, 2022. We selected reports of mathematical cost-effectiveness models comparing POC with SOC for HIV diagnosis in infants younger than 18 months. Titles and abstracts were independently reviewed, with full-text review for qualifying articles. We extracted data on health and economic outcomes and incremental cost-effectiveness ratios (ICERs) for narrative synthesis. The primary outcomes of interest were ICERs (comparing POC with SOC) for ART initiation and survival of children living with HIV.
FINDINGS
Our search identified 75 records through database search. 13 duplicates were excluded, leaving 62 non-duplicate articles. 57 records were excluded and five were reviewed in full text. One article was excluded as it was not a modelling study, and four qualifying studies were included in the review. These four reports were from two mathematical models from two independent modelling groups. Two reports used the Johns Hopkins model to compare POC with SOC for repeat early infant diagnosis testing in the first 6 months in sub-Saharan Africa (first report, simulation of 25 000 children) and Zambia (second report, simulation of 7500 children). In the base scenario, POC versus SOC increased probability of ART initiation within 60 days of testing from 19% to 82% (ICER per additional ART initiation range US$430-1097; 9-month cost horizon) in the first report; and from 28% to 81% in the second ($23-1609, 5-year cost horizon). Two reports compared POC with SOC for testing at 6 weeks in Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Paediatric model (simulation of 30 million children; lifetime horizon). POC increased life expectancy and was considered cost-effective compared with SOC (ICER $711-850 per year of life saved in HIV-exposed children). Results were robust throughout sensitivity and scenario analyses. In most scenarios, platform cost-sharing (co-use with other programmes) resulted in POC being cost-saving compared with SOC.
INTERPRETATION
Four reports from two different models suggest that POC is a cost-effective and potentially cost-saving strategy for upscaling of early infant testing compared with SOC.
FUNDING
Bill & Melinda Gates Foundation, Unitaid, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, WHO, and Massachusetts General Hospital Research Scholars.
Topics: Child; Humans; State Medicine; HIV Infections; Point-of-Care Systems; Point-of-Care Testing; Early Diagnosis; Cost-Benefit Analysis; Acquired Immunodeficiency Syndrome
PubMed: 37149292
DOI: 10.1016/S2352-3018(23)00029-2 -
BMJ Open Respiratory Research Apr 2023Despite chronic obstructive pulmonary disease (COPD) being a major global cause of mortality and hospitalisation, it is often undiagnosed or inaccurately diagnosed in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite chronic obstructive pulmonary disease (COPD) being a major global cause of mortality and hospitalisation, it is often undiagnosed or inaccurately diagnosed in clinical settings.
OBJECTIVE
To systematically synthesise all peer-reviewed papers from primary healthcare settings that have reported data on: (1) undiagnosed COPD, that is, patients with respiratory symptoms and postbronchodilator airflow obstruction consistent with COPD, without a formal clinician's diagnosis of COPD either documented in health records or reported by patients and (2) 'overdiagnosed COPD', that is, clinician's diagnosis without postbronchodilator airflow obstruction.
METHODS
Studies investigating these diagnostic metrics in patients from primary healthcare clinics (according to predefined inclusion/exclusion criteria) were sourced from Medline and Embase and assessed for bias (Johanna Briggs Institute tools for prevalence studies and case series). Meta-analyses of studies of adequate sample size used random effect modelling stratified by risk factor categories.
RESULTS
Of 26 eligible articles, 21 cross-sectional studies investigated 3959 cases of spirometry-defined COPD (with or without symptoms), and 5 peer-reviewed COPD case series investigated 7381 patients. The prevalence of spirometry-confirmed COPD without a diagnosis documented in their health records was 14%-26% in studies of symptomatic smokers (N=3). 1 in 4 patients taking inhaled therapies (25% (95% CI 22% to 28%), N=2) and 1 in 6 smokers irrespective of symptoms (16% (95% CI 14% to 18%), N=6) fulfilled diagnostic spirometry criteria but did not report receiving a COPD-related diagnosis. In an adequately powered series of COPD cases documented in primary healthcare records (N=4), only between 50% and 75% of subjects had any airflow obstruction on postbronchodilator spirometry performed by study researchers, therefore, COPD was clinically 'overdiagnosed' in 25%-50% of subjects.
DISCUSSION
Although data were heterogeneous and of modest quality, undiagnosed COPD was common in primary healthcare, especially for symptomatic smokers and patients treated with inhaled therapies. In contrast, frequent COPD 'overdiagnosis' may represent treatment of asthma/reversible component or another medical diagnosis.
PROSPERO REGISTRATION NUMBER
CRD42022295832.
Topics: Humans; Cross-Sectional Studies; Smoking; Pulmonary Disease, Chronic Obstructive; Spirometry; Primary Health Care
PubMed: 37130651
DOI: 10.1136/bmjresp-2022-001478 -
The Cochrane Database of Systematic... Apr 2023Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an... (Review)
Review
BACKGROUND
Clostridioides difficile (formerly known as Clostridium difficile) is a bacterium that can cause potentially life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis, and can cause recurrent infections in nearly a third of infected individuals. The traditional treatment of recurrent C difficile infection (rCDI) includes antibiotics, which may further exacerbate dysbiosis. There is growing interest in correcting the underlying dysbiosis in rCDI using of fecal microbiota transplantation (FMT); and there is a need to establish the benefits and harms of FMT for the treatment of rCDI based on data from randomized controlled trials.
OBJECTIVES
To evaluate the benefits and harms of donor-based fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile infection in immunocompetent people.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 31 March 2022.
SELECTION CRITERIA
We considered randomized trials of adults or children with rCDI for inclusion. Eligible interventions must have met the definition of FMT, which is the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a person with rCDI. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, no intervention, or antibiotics with activity against C difficile.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. proportion of participants with resolution of rCDI and 2. serious adverse events. Our secondary outcomes were 3. treatment failure, 4. all-cause mortality, 5. withdrawal from study, 6. rate of new CDI infection after a successful FMT, 7. any adverse event, 8. quality of life, and 9. colectomy. We used the GRADE criteria to assess certainty of evidence for each outcome.
MAIN RESULTS
We included six studies with 320 participants. Two studies were conducted in Denmark, and one each in the Netherlands, Canada, Italy, and the US. Four were single-center and two were multicenter studies. All studies included only adults. Five studies excluded people who were severely immunocompromised, with only one study including 10 participants who were receiving immunosuppressive therapy out of the 64 enrolled; these were similarly distributed between the FMT arm (4/24 or 17%) and comparison arms (6/40 or 15%). The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery, depending on a clinical determination of whether the recipient could tolerate a colonoscopy. Five studies had at least one comparison group that received vancomycin. The risk of bias (RoB 2) assessments did not find an overall high risk of bias for any outcome. All six studies assessed the efficacy and safety of FMT for the treatment of rCDI. Pooled results from six studies showed that the use of FMT in immunocompetent participants with rCDI likely leads to a large increase in resolution of rCDI in the FMT group compared to control (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71; P = 0.02, I = 63%; 6 studies, 320 participants; number needed to treat for an additional beneficial outcome (NNTB) 3; moderate-certainty evidence). Fecal microbiota transplantation probably results in a slight reduction in serious adverse events; however, the CIs around the summary estimate were wide (RR 0.73, 95% CI 0.38 to 1.41; P = 0.24, I² = 26%; 6 studies, 320 participants; NNTB 12; moderate-certainty evidence). Fecal microbiota transplantation may result in a reduction in all-cause mortality; however, the number of events was small, and the CIs of the summary estimate were wide (RR 0.57, 95% CI 0.22 to 1.45; P = 0.48, I = 0%; 6 studies, 320 participants; NNTB 20; low-certainty evidence). None of the included studies reported colectomy rates.
AUTHORS' CONCLUSIONS
In immunocompetent adults with rCDI, FMT likely leads to a large increase in the resolution of recurrent Clostridioides difficile infection compared to alternative treatments such as antibiotics. There was no conclusive evidence regarding the safety of FMT for the treatment of rCDI as the number of events was small for serious adverse events and all-cause mortality. Additional data from large national registry databases might be required to assess any short-term or long-term risks with using FMT for the treatment of rCDI. Elimination of the single study that included some immunocompromised people did not alter these conclusions. Due to the low number of immunocompromised participants enrolled, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population.
Topics: Adult; Child; Humans; Fecal Microbiota Transplantation; Clostridioides difficile; Clostridioides; Quality of Life; Dysbiosis; Recurrence; Anti-Bacterial Agents; Clostridium Infections; Treatment Outcome
PubMed: 37096495
DOI: 10.1002/14651858.CD013871.pub2