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Infectious Diseases of Poverty Oct 2021Severe dengue is a life-threatening complication; rapid identification of these cases, followed by adequate management is crucial to improve the clinical prognosis.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Severe dengue is a life-threatening complication; rapid identification of these cases, followed by adequate management is crucial to improve the clinical prognosis. Therefore, this study aimed to identify risk factors and predictors of severe dengue.
METHODS
A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed, Scopus and Web of Science database from inception to December 31, 2020. Pooled odds ratios (ORs) for patients' demographic characteristics, co-morbidities, and warning signs were estimated using an inverse variance heterogeneity model.
RESULTS
We included 143 articles in the meta-analysis from a total of 13 090 articles retrieved from the literature search. The risk factors of severe dengue were: being a child [OR = 1.96; 95% confidence interval (CI): 1.22-3.13], secondary infection (OR = 3.23; 95% CI: 2.28-4.57), and patients with pre-existing diabetes (OR = 2.88; 95% CI: 1.72-4.81) and renal disease (OR = 4.54; 95% CI: 1.55-13.31). Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count (OR = 5.13; 95% CI: 1.61-16.34), abdominal pain (OR = 2.00; 95% CI: 1.49-2.68), lethargy (OR = 2.73; 95% CI: 1.05-7.10), vomiting (OR = 1.80; 95% CI: 1.43-2.26), hepatomegaly (OR = 5.92; 95% CI: 3.29-10.66), ascites (OR = 6.30; 95% CI: 3.75-10.60), pleural effusion (OR = 5.72; 95% CI: 3.24-10.10) and melena (OR = 4.05; 95% CI: 1.64-10.00).
CONCLUSIONS
Our meta-analysis identified children, secondary infection, diabetes and renal disease(s) as important predictors of severe dengue. Our finding also supports the predictive ability of the WHO warning signs to identify severe dengue. These findings are useful for clinicians to identify severe dengue for management and timely interventions.
Topics: Humans; Risk Factors; Severe Dengue
PubMed: 34627388
DOI: 10.1186/s40249-021-00908-2 -
The Cochrane Database of Systematic... Sep 2021Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia.
OBJECTIVES
To determine the efficacy and safety of cannabinoids for the treatment of dementia.
SEARCH METHODS
We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates.
MAIN RESULTS
We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains. The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants). We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis. There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness.
AUTHORS' CONCLUSIONS
Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.
Topics: Activities of Daily Living; Aged; Alzheimer Disease; Cannabidiol; Cannabinoids; Dementia, Vascular; Humans
PubMed: 34532852
DOI: 10.1002/14651858.CD012820.pub2 -
International Journal of Environmental... Feb 2023Autism spectrum disorder (ASD) has become a critical public health issue that affects more than 78 million people. In many recent studies, the authors have demonstrated... (Meta-Analysis)
Meta-Analysis Review
Autism spectrum disorder (ASD) has become a critical public health issue that affects more than 78 million people. In many recent studies, the authors have demonstrated that equine-assisted activities and therapies (EAATs) can substantially improve the social and behavioral skills of children with ASD. However, the qualities of the studies differ, and some authors reached opposite conclusions. In this review, we systematically and objectively examined the effectiveness of EAATs for people with ASD, combining both qualitative and quantitative methods. We searched five databases (PubMed, Scopus, ERIC, ProQuest, and MEDLINE) and added relevant references, and we identified 25 articles for data extraction and analysis. According to our results, EAAT programs can substantially improve the social and behavioral functioning and language abilities of children with ASD. However, among the subdomains, the results were inconsistent. According to the meta-analyses, there were considerable improvements in the social cognition, communication, irritability, and hyperactivity domains, but not in the domains of social awareness, mannerisms, motivation, lethargy, stereotypy, or inappropriate speech. Moreover, there was a lack of sufficient comparative data to conclude that EAAT programs lead to substantial improvements in motor and sensory functioning. In addition, among the included studies, we noted the indicator of whether EAAT programs decreased parental stress and improved family functioning, and although there were four articles in which the researchers considered this aspect, we were unable to draw any conclusions because of the insufficient data and conflicting descriptive evidence. However, we need to consider the improvement in parental mental health as a factor in the effectiveness of this complementary intervention. We hope that in future studies, researchers will focus on family functioning and conduct more randomized controlled trials (RCTs) with blinded assessments using different scales and measures.
Topics: Humans; Animals; Horses; Autism Spectrum Disorder; Irritable Mood; Communication; Speech; Equine-Assisted Therapy
PubMed: 36767996
DOI: 10.3390/ijerph20032630 -
JAMA Pediatrics Dec 2022Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer course of antibiotics for nonsevere childhood community-acquired pneumonia (CAP).
OBJECTIVE
To determine whether a shorter course of antibiotics was noninferior to a longer course for childhood nonsevere CAP.
DATA SOURCES
MEDLINE, Embase, Web of Science, the Cochrane Library, and 3 Chinese databases from inception to March 31, 2022, as well as clinical trial registries and Google.com.
STUDY SELECTION
Randomized clinical trials comparing a shorter- vs longer-course therapy using the same oral antibiotic for children with nonsevere CAP were included.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were used to pool the data, which were analyzed from April 15, 2022, to May 15, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence.
MAIN OUTCOMES AND MEASURES
Treatment failure, defined by persistence of pneumonia or the new appearance of any general danger signs of CAP (eg, lethargy, unconsciousness, seizures, or inability to drink), elevated temperature (>38 °C) after completion of treatment, change of antibiotic, hospitalization, death, missing more than 3 study drug doses, loss to follow-up, or withdrawal of informed consent.
RESULTS
Nine randomized clinical trials including 11 143 participants were included in this meta-analysis. A total of 98% of the participants were aged 2 to 59 months, and 58% were male. Eight studies with 10 662 patients reported treatment failure. Treatment failure occurred in 12.8% vs 12.6% of participants randomized to a shorter vs a longer course of antibiotics. High-quality evidence showed that a shorter course of oral antibiotic was noninferior to a longer course with respect to treatment failure for children with nonsevere CAP (risk ratio, 1.01; 95% CI, 0.92-1.11; risk difference, 0.00; 95% CI, -0.01 to 0.01; I2 = 0%). A 3-day course of antibiotic treatment was noninferior to a 5-day course for the outcome of treatment failure (risk ratio, 1.01; 95% CI, 0.91-1.12; I2 = 0%), and a 5-day course was noninferior to a 10-day course (risk ratio, 0.87; 95% CI, 0.50-1.53; I2 = 0%). A shorter course of antibiotics was associated with fewer reports of gastroenteritis (risk ratio, 0.79; 95% CI, 0.66-0.95) and lower caregiver absenteeism (incident rate ratio, 0.74; 95% CI, 0.65-0.84).
CONCLUSIONS AND RELEVANCE
Results of this meta-analysis suggest that a shorter course of antibiotics was noninferior to a longer course in children aged 2 to 59 months with nonsevere CAP. Clinicians should consider prescribing a shorter course of antibiotics for the management of pediatric nonsevere CAP.
Topics: Humans; Male; Child; Female; Community-Acquired Infections; Pneumonia; Anti-Bacterial Agents; Fever; Randomized Controlled Trials as Topic
PubMed: 36374480
DOI: 10.1001/jamapediatrics.2022.4123 -
The Cochrane Database of Systematic... Apr 2019Urinary tract infection (UTI) is common in children. Symptoms include fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary tract infection (UTI) is common in children. Symptoms include fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment is a course of antibiotics. Due to acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term (several months to 2 years) antibiotics aimed at preventing recurrence. This is the third update of a review first published in 2001 and updated in 2006, and 2011.
OBJECTIVES
To assess whether long-term antibiotic prophylaxis was more effective than placebo/no treatment in preventing recurrence of UTI in children, and if so which antibiotic in clinical use was the most effective. We also assessed the harms of long-term antibiotic treatment.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 30 July 2018 through contact with the Cochrane Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised comparisons of antibiotics with other antibiotics, placebo or no treatment to prevent recurrent UTI in children.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed and extracted information for the initial and previous updates. A random-effects model was used to estimate risk ratio (RR) and risk difference (RD) for recurrent UTI with 95% confidence intervals (CI).
MAIN RESULTS
In this update sixteen studies (2036 children randomised, 1977 analysed) were included. Seven studies (612 children) compared two or more types of antibiotics, six (1088 children) compared antibiotics with placebo or no treatment, one four-armed study compared circumcision with and without antibiotic treatment, one study compared dose of antibiotic, and one three-armed study compared two different antibiotics as well as no treatment. Of the sixteen included studies only one study was judged to be at low risk of bias for all domains, with the majority judged to be at unclear risk of bias due to very poorly reported methodology. The number of studies judged to be a low risk of bias was: selection bias (7); performance bias (4); detection bias (1); attrition bias (6); reporting bias (7); and other bias (2). The number of studies judged to be at high risk of bias was: selection bias (0); performance bias (5); detection bias (1); attrition bias (4); reporting bias (6); and other bias (1).Compared to placebo/no treatment, antibiotics lead to a modest decrease in the number of repeat symptomatic UTI in children; however the estimate from combining all studies was not certain and the confidence interval indicates low precision indicating that antibiotics may make little or no difference to risk of repeat infection (RR 0.75, 95% CI 0.28 to 1.98). When we combined only the data from studies with concealed treatment allocation, there was a similar reduction in risk of repeat symptomatic UTI in children taking antibiotics (RR 0.68) and we have greater certainty in this estimate because of the more robust study designs, the confidence interval is smaller and it does not include the point of no effect (95% CI 0.48 to 0.95). The estimated reduction in risk of repeat symptomatic UTI for children taking antibiotics was similar in children with vesicoureteric reflux (VUR) (RR 0.65, 95% CI 0.39 to 1.07) compared to those without VUR (RR 0.56, 95% CI 0.15 to 2.12) however there was considerable uncertainty due to imprecision from fewer events in the smaller group of children with VUR. There was no consistency in occurrence of adverse events, with one study having more events in the placebo group and a second study having more events in the antibiotics group. Three studies reported data for antibiotic resistance with the analysis estimating the risk of a UTI caused by a bacteria resistant to the prophylactic antibiotic being almost 2.5 times greater in children on antibiotics than for children on placebo or no treatment (RR 2.40, 95% CI 0.62 to 9.26). However the confidence interval is wide, showing imprecision and there may be little or no difference between the two groups.Eight studies involving 659 children compared one antibiotic with another but few studies compared the same combination for the same outcome so little data could be pooled. Two studies reported microbial resistance data and analysis showed that treatment with nitrofurantoin may lead to a lower risk of a UTI caused by a bacteria resistant to the treatment drug compared to children given trimethoprim-sulphamethoxazole as their prophylactic treatment (RR 0.54, 95% CI 0.31 to 0.92).
AUTHORS' CONCLUSIONS
Long-term antibiotics may reduce the risk of repeat symptomatic UTI in children who have had one or more previous UTIs but the benefit may be small and must be considered together with the increased risk of microbial resistance.
Topics: Anti-Infective Agents, Urinary; Antibiotic Prophylaxis; Child; Drug Therapy, Combination; Female; Humans; Male; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Urinary Tract Infections; Vesico-Ureteral Reflux
PubMed: 30932167
DOI: 10.1002/14651858.CD001534.pub4 -
Orphanet Journal of Rare Diseases Mar 2015Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a... (Review)
Review
BACKGROUND
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive disorder of the urea cycle. HHH has a panethnic distribution, with a major prevalence in Canada, Italy and Japan. Acute clinical signs include intermittent episodes of vomiting, confusion or coma and hepatitis-like attacks. Alternatively, patients show a chronic course with aversion for protein rich foods, developmental delay/intellectual disability, myoclonic seizures, ataxia and pyramidal dysfunction. HHH syndrome is caused by impaired ornithine transport across the inner mitochondrial membrane due to mutations in SLC25A15 gene, which encodes for the mitochondrial ornithine carrier ORC1. The diagnosis relies on clinical signs and the peculiar metabolic triad of hyperammonemia, hyperornithinemia, and urinary excretion of homocitrulline. HHH syndrome enters in the differential diagnosis with other inherited or acquired conditions presenting with hyperammonemia.
METHODS
A systematic review of publications reporting patients with HHH syndrome was performed.
RESULTS
We retrospectively evaluated the clinical, biochemical and genetic profile of 111 HHH syndrome patients, 109 reported in 61 published articles, and two unpublished cases. Lethargy and coma are frequent at disease onset, whereas pyramidal dysfunction and cognitive/behavioural abnormalities represent the most common clinical features in late-onset cases or during the disease course. Two common mutations, F188del and R179* account respectively for about 30% and 15% of patients with the HHH syndrome. Interestingly, the majority of mutations are located in residues that have side chains protruding into the internal pore of ORC1, suggesting their possible interference with substrate translocation. Acute and chronic management consists in the control of hyperammonemia with protein-restricted diet supplemented with citrulline/arginine and ammonia scavengers. Prognosis of HHH syndrome is variable, ranging from a severe course with disabling manifestations to milder variants compatible with an almost normal life.
CONCLUSIONS
This paper provides detailed information on the clinical, metabolic and genetic profiles of all HHH syndrome patients published to date. The clinical phenotype is extremely variable and its severity does not correlate with the genotype or with recorded ammonium/ornithine plasma levels. Early intervention allows almost normal life span but the prognosis is variable, suggesting the need for a better understanding of the still unsolved pathophysiology of the disease.
Topics: Aging; Humans; Hyperammonemia; Mutation; Origin Recognition Complex; Ornithine; Protein Conformation; Urea Cycle Disorders, Inborn
PubMed: 25874378
DOI: 10.1186/s13023-015-0242-9 -
Scientific Reports Nov 2021Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters... (Meta-Analysis)
Meta-Analysis
Different studies have suggested that fluoride is related to neurological disorders in children and adolescents, but clinical evidences of which neurological parameters associated to fluoride exposure are, in fact, still controversial. In this way, this systematic review and meta-analysis aimed to show if there is an association between fluoride exposure from different sources, doses and neurological disorders. Terms related to "Humans"; "Central nervous system"; "Fluorides"; and "Neurologic manifestations" were searched in a systematic way on PubMed, Scopus, Web of Science, Lilacs, Cochrane and Google Scholar. All studies performed on humans exposed to fluoride were included on the final assessment. A meta-analysis was then performed and the quality level of evidence was performed using the GRADE approach. Our search retrieved 4,024 studies, among which 27 fulfilled the eligibility criteria. The main source of fluoride was naturally fluoridated water. Twenty-six studies showed alterations related to Intelligence Quotient (IQ) while only one has evaluated headache, insomnia, lethargy, polydipsia and polyuria. Ten studies were included on the meta-analysis, which showed IQ impairment only for individuals under high fluoride exposure considering the World Health Organization criteria, without evidences of association between low levels and any neurological disorder. However, the high heterogeneity observed compromise the final conclusions obtained by the quantitative analyses regarding such high levels. Furthermore, this association was classified as very low-level evidence. At this time, the current evidence does not allow us to state that fluoride is associated with neurological damage, indicating the need for new epidemiological studies that could provide further evidences regarding this possible association.
Topics: Adolescent; Child; Environment; Environmental Exposure; Fluoridation; Fluorides; Fluorine Compounds; Humans; Intelligence Tests; Nervous System Diseases
PubMed: 34811523
DOI: 10.1038/s41598-021-99688-w -
Clinical Autonomic Research : Official... Aug 2021Dyskinesia-hyperpyrexia syndrome (DHS) is a rare but life-threatening disease. The clinical manifestations of this syndrome overlap substantially with Parkinson... (Review)
Review
PURPOSE
Dyskinesia-hyperpyrexia syndrome (DHS) is a rare but life-threatening disease. The clinical manifestations of this syndrome overlap substantially with Parkinson hyperpyrexia syndrome and serotonin syndrome and are often confused by clinicians. The purpose of this review was to enable clinicians to recognize this syndrome and thereby reach a correct diagnosis and provide optimal treatments to improve prognosis in clinical practice.
METHODS
Using the methodology described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a literature search of the PubMed, Embase, and MEDLINE databases using keywords in titles and abstracts of published literature. Quality assessment was performed using the modified Newcastle-Ottawa scale.
RESULTS
A total of 11 patients obtained from nine publications were included in this systematic review. All of the cases occurred in patients with advanced Parkinson's disease (PD) of long disease duration. High ambient temperature was the most common trigger of this syndrome. Hyperpyrexia and dyskinesias were present in all cases. The consciousness disturbances of this syndrome included confusion, hallucination, and lethargy or stupor. Autonomic dysfunction (except for hyperpyrexia) is uncommon in DHS, and only two patients presented with tachycardia. The treatment of this syndrome included supportive interventions (including rehydration, anti-pyretic and anti-infection treatments, and maintaining electrolyte balance), dopaminergic drug reduction and sedation. Two patients died due to DHS.
CONCLUSIONS
We summarized the triggers, clinical features, and treatments of all reported dyskinesia-hyperpyrexia syndrome cases, proposed guiding diagnostic criteria, and established a flow chart to guide diagnoses to quickly identify these three syndromes in clinical practice.
Topics: Dyskinesias; Humans; Parkinson Disease; Syndrome
PubMed: 33826041
DOI: 10.1007/s10286-021-00801-w -
Effects of Risperidone in Autistic Children and Young Adults: A Systematic Review and Meta-Analysis.Current Neuropharmacology 2021There are several studies investigating the effects of risperidone on autism, but many of these studies are contradictory or inconclusive. This systematic review and... (Meta-Analysis)
Meta-Analysis
There are several studies investigating the effects of risperidone on autism, but many of these studies are contradictory or inconclusive. This systematic review and meta-analysis investigated the effects of risperidone on five domains of the Aberrant Behaviour Checklist (ABC) scale on Autism Spectrum Disorder (ASD), as well as weight gain and waist circumference. The protocol for the present systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). For this study, we analysed articles (2,459), selecting them according to the PICOS strategy (Population, Intervention, Comparison, Outcome, Study design). Although risperidone is effective for the treatment of lethargy and inadequate speech, concerns about the association between weight gain, waist circumference and risperidone require a need for evaluation of the risk-benefit ratio in its use. There was a significant association between weight gain, waist circumference and risperidone. In conclusion, it was possible to suggest the efficacy of risperidone for the treatment of lethargy and inadequate speech. Finally, we emphasize that the risk-benefit in its use should be evaluated (Protocol number CRD42019122316).
Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Child; Female; Humans; Male; Risperidone; Treatment Outcome; Weight Gain; Young Adult
PubMed: 32469700
DOI: 10.2174/1570159X18666200529151741