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Clinical Infectious Diseases : An... Apr 2021Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in... (Meta-Analysis)
Meta-Analysis
Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.
Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4-100) and 94.1% (88.3-98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2-99.6) and 99.3% (96.7-99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97-99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.
Topics: AIDS-Related Opportunistic Infections; Adult; Antigens, Fungal; Cryptococcus; Diagnostic Tests, Routine; HIV; HIV Infections; Humans; Meningitis, Cryptococcal
PubMed: 32829406
DOI: 10.1093/cid/ciaa1243 -
The Cochrane Database of Systematic... Sep 2022Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert... (Review)
Review
BACKGROUND
Every year, an estimated one million children and young adolescents become ill with tuberculosis, and around 226,000 of those children die. Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects Mycobacterium tuberculosis complex and rifampicin resistance. We previously published a Cochrane Review 'Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for tuberculosis disease and rifampicin resistance in children'. The current review updates evidence on the diagnostic accuracy of Xpert Ultra in children presumed to have tuberculosis disease. Parts of this review update informed the 2022 WHO updated guidance on management of tuberculosis in children and adolescents.
OBJECTIVES
To assess the diagnostic accuracy of Xpert Ultra for detecting: pulmonary tuberculosis, tuberculous meningitis, lymph node tuberculosis, and rifampicin resistance, in children with presumed tuberculosis. Secondary objectives To investigate potential sources of heterogeneity in accuracy estimates. For detection of tuberculosis, we considered age, comorbidity (HIV, severe pneumonia, and severe malnutrition), and specimen type as potential sources. To summarize the frequency of Xpert Ultra trace results.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, three other databases, and three trial registers without language restrictions to 9 March 2021.
SELECTION CRITERIA
Cross-sectional and cohort studies and randomized trials that evaluated Xpert Ultra in HIV-positive and HIV-negative children under 15 years of age. We included ongoing studies that helped us address the review objectives. We included studies evaluating sputum, gastric, stool, or nasopharyngeal specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), and fine needle aspirate or surgical biopsy tissue (lymph node tuberculosis). For detecting tuberculosis, reference standards were microbiological (culture) or composite reference standard; for stool, we also included Xpert Ultra performed on a routine respiratory specimen. For detecting rifampicin resistance, reference standards were drug susceptibility testing or MTBDRplus.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and, using QUADAS-2, assessed methodological quality judging risk of bias separately for each target condition and reference standard. For each target condition, we used the bivariate model to estimate summary sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We summarized the frequency of Xpert Ultra trace results; trace represents detection of a very low quantity of Mycobacterium tuberculosis DNA. We assessed certainty of evidence using GRADE.
MAIN RESULTS
We identified 14 studies (11 new studies since the previous review). For detection of pulmonary tuberculosis, 335 data sets (25,937 participants) were available for analysis. We did not identify any studies that evaluated Xpert Ultra accuracy for tuberculous meningitis or lymph node tuberculosis. Three studies evaluated Xpert Ultra for detection of rifampicin resistance. Ten studies (71%) took place in countries with a high tuberculosis burden based on WHO classification. Overall, risk of bias was low. Detection of pulmonary tuberculosis Sputum, 5 studies Xpert Ultra summary sensitivity verified by culture was 75.3% (95% CI 64.3 to 83.8; 127 participants; high-certainty evidence), and specificity was 97.1% (95% CI 94.7 to 98.5; 1054 participants; high-certainty evidence). Gastric aspirate, 7 studies Xpert Ultra summary sensitivity verified by culture was 70.4% (95% CI 53.9 to 82.9; 120 participants; moderate-certainty evidence), and specificity was 94.1% (95% CI 84.8 to 97.8; 870 participants; moderate-certainty evidence). Stool, 6 studies Xpert Ultra summary sensitivity verified by culture was 56.1% (95% CI 39.1 to 71.7; 200 participants; moderate-certainty evidence), and specificity was 98.0% (95% CI 93.3 to 99.4; 1232 participants; high certainty-evidence). Nasopharyngeal aspirate, 4 studies Xpert Ultra summary sensitivity verified by culture was 43.7% (95% CI 26.7 to 62.2; 46 participants; very low-certainty evidence), and specificity was 97.5% (95% CI 93.6 to 99.0; 489 participants; high-certainty evidence). Xpert Ultra sensitivity was lower against a composite than a culture reference standard for all specimen types other than nasopharyngeal aspirate, while specificity was similar against both reference standards. Interpretation of results In theory, for a population of 1000 children: • where 100 have pulmonary tuberculosis in sputum (by culture): - 101 would be Xpert Ultra-positive, and of these, 26 (26%) would not have pulmonary tuberculosis (false positive); and - 899 would be Xpert Ultra-negative, and of these, 25 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in gastric aspirate (by culture): - 123 would be Xpert Ultra-positive, and of these, 53 (43%) would not have pulmonary tuberculosis (false positive); and - 877 would be Xpert Ultra-negative, and of these, 30 (3%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in stool (by culture): - 74 would be Xpert Ultra-positive, and of these, 18 (24%) would not have pulmonary tuberculosis (false positive); and - 926 would be Xpert Ultra-negative, and of these, 44 (5%) would have tuberculosis (false negative). • where 100 have pulmonary tuberculosis in nasopharyngeal aspirate (by culture): - 66 would be Xpert Ultra-positive, and of these, 22 (33%) would not have pulmonary tuberculosis (false positive); and - 934 would be Xpert Ultra-negative, and of these, 56 (6%) would have tuberculosis (false negative). Detection of rifampicin resistance Xpert Ultra sensitivity was 100% (3 studies, 3 participants; very low-certainty evidence), and specificity range was 97% to 100% (3 studies, 128 participants; low-certainty evidence). Trace results Xpert Ultra trace results, regarded as positive in children by WHO standards, were common. Xpert Ultra specificity remained high in children, despite the frequency of trace results.
AUTHORS' CONCLUSIONS
We found Xpert Ultra sensitivity to vary by specimen type, with sputum having the highest sensitivity, followed by gastric aspirate and stool. Nasopharyngeal aspirate had the lowest sensitivity. Xpert Ultra specificity was high against both microbiological and composite reference standards. However, the evidence base is still limited, and findings may be imprecise and vary by study setting. Although we found Xpert Ultra accurate for detection of rifampicin resistance, results were based on a very small number of studies that included only three children with rifampicin resistance. Therefore, findings should be interpreted with caution. Our findings provide support for the use of Xpert Ultra as an initial rapid molecular diagnostic in children being evaluated for tuberculosis.
Topics: Adolescent; Antibiotics, Antitubercular; Child; Cross-Sectional Studies; HIV Infections; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary
PubMed: 36065889
DOI: 10.1002/14651858.CD013359.pub3 -
The Cochrane Database of Systematic... Mar 2022Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review.
OBJECTIVES
To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation.
DATA COLLECTION AND ANALYSIS
For this update, two review authors independently assessed studies for inclusion resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence.
MAIN RESULTS
The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was about 33 months. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence). Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 children; high-certainty evidence). There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis. VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies, 19,566 children; moderate-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence). However, there was no evidence of a difference on incidence of respiratory disease (RR 0.99, 95% CI 0.92 to 1.06; 11 studies, 27,540 children; low-certainty evidence) or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies, 10,541 children; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
This update identified no new eligible studies and the conclusions remain the same. VAS is associated with a clinically meaningful reduction in morbidity and mortality in children. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented VAD, it would be unethical to conduct placebo-controlled trials.
Topics: Child; Child, Preschool; Diarrhea; Dietary Supplements; Female; Humans; Male; Measles; Morbidity; Respiration Disorders; Vitamin A; Vitamin A Deficiency
PubMed: 35294044
DOI: 10.1002/14651858.CD008524.pub4 -
The Cochrane Database of Systematic... Aug 2018Mechanical chest compression devices have been proposed to improve the effectiveness of cardiopulmonary resuscitation (CPR).
BACKGROUND
Mechanical chest compression devices have been proposed to improve the effectiveness of cardiopulmonary resuscitation (CPR).
OBJECTIVES
To assess the effectiveness of resuscitation strategies using mechanical chest compressions versus resuscitation strategies using standard manual chest compressions with respect to neurologically intact survival in patients who suffer cardiac arrest.
SEARCH METHODS
On 19 August 2017 we searched the Cochrane Central Register of Controlled Studies (CENTRAL), MEDLINE, Embase, Science Citation Index-Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science databases. Biotechnology and Bioengineering Abstracts and Science Citation abstracts had been searched up to November 2009 for prior versions of this review. We also searched two clinical trials registries for any ongoing trials not captured by our search of databases containing published works: Clinicaltrials.gov (August 2017) and the World Health Organization International Clinical Trials Registry Platform portal (January 2018). We applied no language restrictions. We contacted experts in the field of mechanical chest compression devices and manufacturers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-RCTs and quasi-randomised studies comparing mechanical chest compressions versus manual chest compressions during CPR for patients with cardiac arrest.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included five new studies in this update. In total, we included 11 trials in the review, including data from 12,944 adult participants, who suffered either out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA). We excluded studies explicitly including patients with cardiac arrest caused by trauma, drowning, hypothermia and toxic substances. These conditions are routinely excluded from cardiac arrest intervention studies because they have a different underlying pathophysiology, require a variety of interventions specific to the underlying condition and are known to have a prognosis different from that of cardiac arrest with no obvious cause. The exclusions were meant to reduce heterogeneity in the population while maintaining generalisability to most patients with sudden cardiac death.The overall quality of evidence for the outcomes of included studies was moderate to low due to considerable risk of bias. Three studies (N = 7587) reported on the designated primary outcome of survival to hospital discharge with good neurologic function (defined as a Cerebral Performance Category (CPC) score of one or two), which had moderate quality evidence. One study showed no difference with mechanical chest compressions (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.82 to 1.39), one study demonstrated equivalence (RR 0.79, 95% CI 0.60 to 1.04), and one study demonstrated reduced survival (RR 0.41, CI 0.21 to 0.79). Two other secondary outcomes, survival to hospital admission (N = 7224) and survival to hospital discharge (N = 8067), also had moderate quality level of evidence. No studies reported a difference in survival to hospital admission. For survival to hospital discharge, two studies showed benefit, four studies showed no difference, and one study showed harm associated with mechanical compressions. No studies demonstrated a difference in adverse events or injury patterns between comparison groups but the quality of data was low. Marked clinical and statistical heterogeneity between studies precluded any pooled estimates of effect.
AUTHORS' CONCLUSIONS
The evidence does not suggest that CPR protocols involving mechanical chest compression devices are superior to conventional therapy involving manual chest compressions only. We conclude on the balance of evidence that mechanical chest compression devices used by trained individuals are a reasonable alternative to manual chest compressions in settings where consistent, high-quality manual chest compressions are not possible or dangerous for the provider (eg, limited rescuers available, prolonged CPR, during hypothermic cardiac arrest, in a moving ambulance, in the angiography suite, during preparation for extracorporeal CPR [ECPR], etc.). Systems choosing to incorporate mechanical chest compression devices should be closely monitored because some data identified in this review suggested harm. Special attention should be paid to minimising time without compressions and delays to defibrillation during device deployment.
Topics: Blood Circulation; Cardiopulmonary Resuscitation; Heart Arrest; Heart Massage; Hospitalization; Humans; Patient Discharge; Randomized Controlled Trials as Topic
PubMed: 30125048
DOI: 10.1002/14651858.CD007260.pub4 -
The Lancet. Global Health Jan 2021Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs...
BACKGROUND
Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.
METHODS
We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.
FINDINGS
In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.
INTERPRETATION
Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Acute Disease; Child, Preschool; Cost of Illness; Female; Global Health; Humans; Infant; Infant, Newborn; Linear Models; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 33248481
DOI: 10.1016/S2214-109X(20)30393-4 -
EClinicalMedicine Feb 2022The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine...
Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis.
BACKGROUND
The FilmArray Meningitis/Encephalitis(FA/ME) panel brings benefits in clinical practice, but its diagnostic test accuracy (DTA) remains unclear. We aimed to determine the DTA of FA/ME for the aetiological diagnostic in patients with suspected central nervous system(CNS) infection.
METHODS
We performed a systematic review with DTA meta-analysis (PROSPERO: CRD42020139285). We searched Embase, Medline (Ovid), and Web of Science from inception until September 1st, 2021. We assessed the study-level risk of bias with the QUADAS-2 tool and applied the GRADE approach to assess the certainty of the synthesised evidence. We included studies that simultaneously measured the reference test (CSF/blood culture for bacteria, and specific polymerase chain reaction for viruses) and the FA/ME in patients with suspected CNS infection. We performed random-effects bivariate meta-analysis models of combined sensitivity and specificity using CSF/blood cultures(reference test 1) and a final diagnosis adjudication based on clinical/laboratory criteria (reference test 2).
FINDINGS
We included 19 studies (11,351 participants). For all bacteria with reference test 1 (16 studies/6183 patients) sensitivity was estimated at 89·5% (95%CI 81·1-94·4), and specificity at 97·4% (95%CI 94-98·9). With reference test 2 (15 studies/5,524 patients), sensitivity was estimated at 92·1%(95%CI 86·8-95·3) and specificity at 99.2(95%CI 98·3-99·6) For herpes simplex virus-2(HSV-2), enteroviruses, and Varicella-Zoster virus (VZV), we obtained sensitivities between 75·5 and 93·8%, and specificities above 99% (reference test 1). Certainty of the evidence was low.
INTERPRETATION
FA/ME may have acceptable-to-high sensitivities and high specificities for identifying bacteria, especially for , and viruses, especially for HSV-2, and enteroviruses. Sensitivities for L., and HSV-1 were suboptimal.
FUNDING
None.
PubMed: 35198914
DOI: 10.1016/j.eclinm.2022.101275 -
The Lancet. Global Health Apr 2020Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million...
BACKGROUND
Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.
METHODS
We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.
FINDINGS
In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1-190·6), 10·1 million influenza-virus-associated ALRI cases (6·8-15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000-1 415 000), 15 300 in-hospital deaths (5800-43 800), and up to 34 800 (13 200-97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.
INTERPRETATION
A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.
FUNDING
WHO; Bill & Melinda Gates Foundation.
Topics: Child, Preschool; Global Health; Humans; Infant; Infant, Newborn; Influenza, Human; Linear Models; Respiratory Tract Infections; Seasons
PubMed: 32087815
DOI: 10.1016/S2214-109X(19)30545-5 -
The Cochrane Database of Systematic... Jan 2017Prelabour rupture of membranes (PROM) at term is managed expectantly or by planned early birth. It is not clear if waiting for birth to occur spontaneously is better... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prelabour rupture of membranes (PROM) at term is managed expectantly or by planned early birth. It is not clear if waiting for birth to occur spontaneously is better than intervening, e.g. by inducing labour.
OBJECTIVES
The objective of this review is to assess the effects of planned early birth (immediate intervention or intervention within 24 hours) when compared with expectant management (no planned intervention within 24 hours) for women with term PROM on maternal, fetal and neonatal outcomes.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (9 September 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials of planned early birth compared with expectant management (either in hospital or at home) in women with PROM at 37 weeks' gestation or later.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, extracted the data, and assessed risk of bias of the included studies. Data were checked for accuracy.
MAIN RESULTS
Twenty-three trials involving 8615 women and their babies were included in the update of this review. Ten trials assessed intravenous oxytocin; 12 trials assessed prostaglandins (six trials in the form of vaginal prostaglandin E2 and six as oral, sublingual or vaginal misoprostol); and one trial each assessed Caulophyllum and acupuncture. Overall, three trials were judged to be at low risk of bias, while the other 20 were at unclear or high risk of bias.Primary outcomes: women who had planned early birth were at a reduced risk of maternal infectious morbidity (chorioamnionitis and/or endometritis) than women who had expectant management following term prelabour rupture of membranes (average risk ratio (RR) 0.49; 95% confidence interval (CI) 0.33 to 0.72; eight trials, 6864 women; Tau² = 0.19; I² = 72%; low-quality evidence), and their neonates were less likely to have definite or probable early-onset neonatal sepsis (RR 0.73; 95% CI 0.58 to 0.92; 16 trials, 7314 infants;low-quality evidence). No clear differences between the planned early birth and expectant management groups were seen for the risk of caesarean section (average RR 0.84; 95% CI 0.69 to 1.04; 23 trials, 8576 women; Tau² = 0.10; I² = 55%; low-quality evidence); serious maternal morbidity or mortality (no events; three trials; 425 women; very low-quality evidence); definite early-onset neonatal sepsis (RR 0.57; 95% CI 0.24 to 1.33; six trials, 1303 infants; very low-quality evidence); or perinatal mortality (RR 0.47; 95% CI 0.13 to 1.66; eight trials, 6392 infants; moderate-quality evidence).
SECONDARY OUTCOMES
women who had a planned early birth were at a reduced risk of chorioamnionitis (average RR 0.55; 95% CI 0.37 to 0.82; eight trials, 6874 women; Tau² = 0.19; I² = 73%), and postpartum septicaemia (RR 0.26; 95% CI 0.07 to 0.96; three trials, 263 women), and their neonates were less likely to receive antibiotics (average RR 0.61; 95% CI 0.44 to 0.84; 10 trials, 6427 infants; Tau² = 0.06; I² = 32%). Women in the planned early birth group were more likely to have their labour induced (average RR 3.41; 95% CI 2.87 to 4.06; 12 trials, 6945 women; Tau² = 0.05; I² = 71%), had a shorter time from rupture of membranes to birth (mean difference (MD) -10.10 hours; 95% CI -12.15 to -8.06; nine trials, 1484 women; Tau² = 5.81; I² = 60%), and their neonates had lower birthweights (MD -79.25 g; 95% CI -124.96 to -33.55; five trials, 1043 infants). Women who had a planned early birth had a shorter length of hospitalisation (MD -0.79 days; 95% CI -1.20 to -0.38; two trials, 748 women; Tau² = 0.05; I² = 59%), and their neonates were less likely to be admitted to the neonatal special or intensive care unit (RR 0.75; 95% CI 0.66 to 0.85; eight trials, 6179 infants), and had a shorter duration of hospital (-11.00 hours; 95% CI -21.96 to -0.04; one trial, 182 infants) or special or intensive care unit stay (RR 0.72; 95% CI 0.61 to 0.85; four trials, 5691 infants). Women in the planned early birth group had more positive experiences compared with women in the expectant management group.No clear differences between groups were observed for endometritis; postpartum pyrexia; postpartum antibiotic usage; caesarean for fetal distress; operative vaginal birth; uterine rupture; epidural analgesia; postpartum haemorrhage; adverse effects; cord prolapse; stillbirth; neonatal mortality; pneumonia; Apgar score less than seven at five minutes; use of mechanical ventilation; or abnormality on cerebral ultrasound (no events).None of the trials reported on breastfeeding; postnatal depression; gestational age at birth; meningitis; respiratory distress syndrome; necrotising enterocolitis; neonatal encephalopathy; or disability at childhood follow-up.In subgroup analyses, there were no clear patterns of differential effects for method of induction, parity, use of maternal antibiotic prophylaxis, or digital vaginal examination. Results of the sensitivity analyses based on trial quality were consistent with those of the main analysis, except for definite or probable early-onset neonatal sepsis where no clear difference was observed.
AUTHORS' CONCLUSIONS
There is low quality evidence to suggest that planned early birth (with induction methods such as oxytocin or prostaglandins) reduces the risk of maternal infectious morbidity compared with expectant management for PROM at 37 weeks' gestation or later, without an apparent increased risk of caesarean section. Evidence was mainly downgraded due to the majority of studies contributing data having some serious design limitations, and for most outcomes estimates were imprecise.Although the 23 included trials in this review involved a large number of women and babies, the quality of the trials and evidence was not high overall, and there was limited reporting for a number of important outcomes. Thus further evidence assessing the benefits or harms of planned early birth compared with expectant management, considering maternal, fetal, neonatal and longer-term childhood outcomes, and the use of health services, would be valuable. Any future trials should be adequately designed and powered to evaluate the effects on short- and long-term outcomes. Standardisation of outcomes and their definitions, including for the assessment of maternal and neonatal infection, would be beneficial.
Topics: Cesarean Section; Female; Fetal Membranes, Premature Rupture; Humans; Labor, Induced; Misoprostol; Obstetric Labor Complications; Oxytocics; Oxytocin; Pregnancy; Pregnancy Outcome; Prostaglandins; Randomized Controlled Trials as Topic; Term Birth; Time Factors; Watchful Waiting
PubMed: 28050900
DOI: 10.1002/14651858.CD005302.pub3 -
The Lancet. Global Health Aug 2019Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in...
BACKGROUND
Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.
METHODS
In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.
FINDINGS
We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]).
INTERPRETATION
This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination.
FUNDING
European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Topics: Female; Global Health; Humans; Influenza A virus; Influenza, Human; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 31303294
DOI: 10.1016/S2214-109X(19)30264-5 -
JAMA Network Open Jun 2023A potential relationship between meningioma and breast cancer was suggested 70 years ago. However, to date, no conclusive evidence is available on this topic. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
A potential relationship between meningioma and breast cancer was suggested 70 years ago. However, to date, no conclusive evidence is available on this topic.
OBJECTIVE
To provide a comprehensive review of the literature on the association of meningioma with breast cancer, supported by a meta-analysis.
DATA SOURCES
A systematic PubMed search was performed up to April 2023 to identify articles on the association of meningioma with breast cancer. The following key words were used strategically: meningioma, breast cancer, breast carcinoma, association, relation.
STUDY SELECTION
All studies reporting women diagnosed with meningioma and breast cancer were identified. The search strategy was not limited by study design or publication date but only included articles in English. Additional articles were identified via citation searching. Studies reporting a complete population of meningiomas or breast cancer patients throughout a specific study period and a proportion of patients with a second pathology could be used for the meta-analysis.
DATA EXTRACTION AND SYNTHESIS
Data extraction was performed by 2 authors in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. Meta-analyses regarding both populations were performed using a random-effects model. Risk of bias was assessed.
MAIN OUTCOMES AND MEASURES
The main measures were whether there was an increased prevalence of breast cancer in female patients with meningioma and whether there was an increased prevalence of meningioma in female patients with breast cancer.
RESULTS
A total of 51 retrospective studies (case reports, case series, and cancer registry reports) describing 2238 patients with both diseases were identified; 18 studies qualified for prevalence analyses and meta-analysis. The random-effects meta-analysis (13 studies) revealed a significantly greater prevalence of breast cancer in female patients with meningioma than in the overall population (odds ratio [OR], 9.87; 95% CI, 7.31-13.32). Meningioma incidence in patients with breast cancer (11 studies) was greater than that in the baseline population; however, the difference according to the random-effects model was not statistically significant (OR, 1.41; 95% CI, 0.99-2.02).
CONCLUSIONS AND RELEVANCE
This large systematic review and the meta-analysis on the association between meningioma and breast cancer found nearly 10-fold higher odds of breast cancer in female patients with meningioma compared with the general female population. These findings suggest that female patients with meningioma should be screened more intensively for breast cancer. Further research is required to identify the factors causing this association.
Topics: Humans; Female; Breast Neoplasms; Meningioma; Retrospective Studies; Incidence; Meningeal Neoplasms
PubMed: 37326990
DOI: 10.1001/jamanetworkopen.2023.18620