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Gut Microbes 2013Policy analysis shows that H. pylori test and treat strategies targeting adults at moderate to high risk of H. pylori-induced disease is likely to be cost-effective for... (Review)
Review
Policy analysis shows that H. pylori test and treat strategies targeting adults at moderate to high risk of H. pylori-induced disease is likely to be cost-effective for preventing digestive diseases responsible for a large global disease burden. Little is known, however, about health benefits to children from eliminating this infection. We conducted a systematic review of the evidence regarding health benefits to children from treatment to eliminate H. pylori infection. We systematically searched Ovid MEDLINE for pertinent review articles published through 2012. We excluded reviews focused on treatment efficacy and scrutinized reference lists of selected reviews to identify additional eligible reviews. Fifteen reviews met specified inclusion criteria. Overall, they show that few reported studies investigating pediatric health effects of treatment for H. pylori infection were well designed with adequate statistical power. Thus, there is insufficient evidence for drawing conclusions about health benefits to children from treatment to eliminate H. pylori infection.
Topics: Anemia, Iron-Deficiency; Child; Clinical Trials as Topic; Gastroesophageal Reflux; Growth Disorders; Helicobacter Infections; Helicobacter pylori; Humans; Meta-Analysis as Topic; Purpura, Thrombocytopenic, Idiopathic
PubMed: 24280768
DOI: 10.4161/gmic.27000 -
Kidney International. Supplement Feb 2009Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and... (Review)
Review
Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989-2008).
Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions.
Topics: ADAM Proteins; ADAMTS13 Protein; Adverse Drug Reaction Reporting Systems; Animals; Autoantibodies; Clopidogrel; Epidemiologic Studies; Humans; Plasma Exchange; Platelet Aggregation Inhibitors; Purpura, Thrombotic Thrombocytopenic; Renal Insufficiency; Risk Factors; Ticlopidine; Treatment Outcome
PubMed: 19180126
DOI: 10.1038/ki.2008.613 -
The Cochrane Database of Systematic... Feb 2012Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mumps, measles and rubella (MMR) are serious diseases that can lead to potentially fatal illness, disability and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness.
OBJECTIVES
To assess the effectiveness and adverse effects associated with the MMR vaccine in children up to 15 years of age.
SEARCH METHODS
For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, PubMed (July 2004 to May week 2, 2011) and Embase.com (July 2004 to May 2011).
SELECTION CRITERIA
We used comparative prospective or retrospective trials assessing the effects of the MMR vaccine compared to placebo, do nothing or a combination of measles, mumps and rubella antigens on healthy individuals up to 15 years of age.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed methodological quality of the included studies. One review author arbitrated in case of disagreement.
MAIN RESULTS
We included five randomised controlled trials (RCTs), one controlled clinical trial (CCT), 27 cohort studies, 17 case-control studies, five time-series trials, one case cross-over trial, two ecological studies, six self controlled case series studies involving in all about 14,700,000 children and assessing effectiveness and safety of MMR vaccine. Based on the available evidence, one MMR vaccine dose is at least 95% effective in preventing clinical measles and 92% effective in preventing secondary cases among household contacts.Effectiveness of at least one dose of MMR in preventing clinical mumps in children is estimated to be between 69% and 81% for the vaccine prepared with Jeryl Lynn mumps strain and between 70% and 75% for the vaccine containing the Urabe strain. Vaccination with MMR containing the Urabe strain has demonstrated to be 73% effective in preventing secondary mumps cases. Effectiveness of Jeryl Lynn containing MMR in preventing laboratory-confirmed mumps cases in children and adolescents was estimated to be between 64% to 66% for one dose and 83% to 88% for two vaccine doses. We did not identify any studies assessing the effectiveness of MMR in preventing rubella.The highest risk of association with aseptic meningitis was observed within the third week after immunisation with Urabe-containing MMR (risk ratio (RR) 14.28; 95% confidence interval (CI) from 7.93 to 25.71) and within the third (RR 22.5; 95% CI 11.8 to 42.9) or fifth (RR 15.6; 95% CI 10.3 to 24.2) weeks after immunisation with the vaccine prepared with the Leningrad-Zagreb strain. A significant risk of association with febrile seizures and MMR exposure during the two previous weeks (RR 1.10; 95% CI 1.05 to 1.15) was assessed in one large person-time cohort study involving 537,171 children aged between three months and five year of age. Increased risk of febrile seizure has also been observed in children aged between 12 to 23 months (relative incidence (RI) 4.09; 95% CI 3.1 to 5.33) and children aged 12 to 35 months (RI 5.68; 95% CI 2.31 to 13.97) within six to 11 days after exposure to MMR vaccine. An increased risk of thrombocytopenic purpura within six weeks after MMR immunisation in children aged 12 to 23 months was assessed in one case-control study (RR 6.3; 95% CI 1.3 to 30.1) and in one small self controlled case series (incidence rate ratio (IRR) 5.38; 95% CI 2.72 to 10.62). Increased risk of thrombocytopenic purpura within six weeks after MMR exposure was also assessed in one other case-control study involving 2311 children and adolescents between one month and 18 years (odds ratio (OR) 2.4; 95% CI 1.2 to 4.7). Exposure to the MMR vaccine was unlikely to be associated with autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, bacterial or viral infections.
AUTHORS' CONCLUSIONS
The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunisation with the MMR vaccine cannot be separated from its role in preventing the target diseases.
Topics: Adolescent; Age Factors; Autistic Disorder; Child; Child, Preschool; Clinical Trials as Topic; Crohn Disease; Epidemiologic Studies; Humans; Infant; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Purpura, Thrombocytopenic; Rubella; Seizures, Febrile; Vaccines, Attenuated
PubMed: 22336803
DOI: 10.1002/14651858.CD004407.pub3 -
The Journal of International Medical... Oct 2020We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We reviewed relevant research on rituximab (RTX) treatment for pediatric immune thrombocytopenia (ITP) to elucidate the efficacy and safety of RTX.
METHODS
Prospective clinical trials of RTX for the treatment of pediatric ITP were collected by searching the PubMed, Cochrane Library, Web of Science, and OVID: EMBASE databases and ClinicalTrials.gov. We examined rates of overall response (OR), complete response (CR), partial response (PR), sustained response (SR), relapse (R), and adverse drug reaction (ADR). The Methodological Index for Nonrandomized Studies scale was used, and sensitivity analyses were performed.
RESULTS
For five studies, including 100 patients, the pooled OR, CR, PR, SR, R, and ADR rates were 52% (95% CI: 0.36-0.77, = 78%), 52% (95% CI: 0.41-0.67, = 45%), 18% (95% CI: 0.10-0.33, = 33%), 43% (95% CI: 0.29-0.63, = 0%), 25% (95% CI: 0.06-0.96, = 52%), and 30% (95% CI: 0.15-0.58, = 64%), respectively.
CONCLUSION
There is evidence, albeit low quality, that RTX may be a better second-line therapy than splenectomy for children with ITP; however, its efficacy and safety need to be validated by further high-quality clinical trials, such as randomized controlled trials.
Topics: Child; Humans; Minors; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Thrombocytopenia
PubMed: 33115308
DOI: 10.1177/0300060520962348 -
BMC Infectious Diseases Aug 2010Bacterial meningitis (BM) is a severe infection responsible for high mortality and disabling sequelae. Early identification of patients at high risk of these outcomes is... (Review)
Review
BACKGROUND
Bacterial meningitis (BM) is a severe infection responsible for high mortality and disabling sequelae. Early identification of patients at high risk of these outcomes is necessary to prevent their occurrence by adequate treatment as much as possible. For this reason, several prognostic models have been developed. The objective of this study is to summarize the evidence regarding prognostic factors predicting death or sequelae due to BM in children 0-18 years of age.
METHODS
A search in MEDLINE and EMBASE was conducted to identify prognostic studies on risk factors for mortality and sequelae after BM in children. Selection of abstracts, full-text articles and assessment of methodological quality using the QUIPS checklist was performed by two reviewers independently. Data on prognostic factors per outcome were summarized.
RESULTS
Of the 31 studies identified, 15 were of moderate to high quality. Due to substantial heterogeneity in study characteristics and evaluated prognostic factors, no quantitative analysis was performed. Prognostic factors found to be statistically significant in more than one study of moderate or high quality are: complaints > 48 hours before admission, coma/impaired consciousness, (prolonged duration of) seizures, (prolonged) fever, shock, peripheral circulatory failure, respiratory distress, absence of petechiae, causative pathogen Streptococcus pneumoniae, young age, male gender, several cerebrospinal fluid (CSF) parameters and white blood cell (WBC) count.
CONCLUSIONS
Although several important prognostic factors for the prediction of mortality or sequelae after BM were identified, the inability to perform a pooled analysis makes the exact (independent) predictive value of these factors uncertain. This emphasizes the need for additional well-conducted prognostic studies.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Nervous System Diseases; Prognosis; Risk Factors
PubMed: 20684796
DOI: 10.1186/1471-2334-10-232 -
The Journal of International Medical... Jan 2023To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP).
METHODS
Randomized controlled clinical trials were collected by systematically searching databases (PubMed®, MEDLINE®, EMBASE, The Cochrane Library, China National Knowledge Infrastructure) from inception to June 2022. All studies included patients with ITP who received cyclosporine-based regimens. We performed comprehensive analyses of the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, relapse rate, platelet count, and adverse drug reaction (ADR) rate.
RESULTS
Seven studies (n = 418) were ultimately included. According to a fixed-effects model, cyclosporine-based combinations improved the ORR and CR rate and reduced the relapse rate. The ADR rate was not increased in the cyclosporine-based combination group. Cyclosporine-based regimens effectively increased the platelet count. Subgroup analysis illustrated that cyclosporine-based combinations were linked to higher ORRs in both children (odds ratio [OR] = 5.74, 95% confidence interval [CI] = 1.79-18.41) and adults (OR = 5.46, 95% CI = 2.48-12.02) and a higher CR rate in adults (OR = 2.97, 95% CI = 1.56-5.63).
CONCLUSION
Cyclosporine exhibited efficacy in the treatment of ITP without increasing the risk of ADRs.
Topics: Child; Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Cyclosporine; Platelet Count; Clinical Protocols; Remission Induction
PubMed: 36650914
DOI: 10.1177/03000605221149870 -
The Cochrane Database of Systematic... Aug 2015Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood but may occur in adults. This small vessel vasculitis is characterised by palpable purpura,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood but may occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009.
OBJECTIVES
To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for: (1) the prevention of severe kidney disease in patients with HSP without kidney disease at presentation; (2) the prevention of severe kidney disease in patients with HSP and minor kidney disease (microscopic haematuria, mild proteinuria) at presentation; (3) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in HSP; and (4) the prevention of recurrent episodes of HSP-associated kidney disease.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant's Specialised Register to 13 July 2015 through contact with the Trials Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in HSP compared with placebo, no treatment or other agents were included.
DATA COLLECTION AND ANALYSIS
Two authors independently determined study eligibility, assessed risk of bias and extracted data from each study. Statistical analyses were performed using the random effects model and the results were expressed as risk ratio (RR) or risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI).
MAIN RESULTS
Thirteen studies (1403 enrolled patients) were identified. Risks of bias attributes were frequently poorly performed. Low risk of bias was reported in six studies (50%) for sequence generation (selection bias) and in seven (58%) for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and of outcome assessment (detection bias) was at low risk of bias in three studies. Five studies reported complete outcome data (attrition bias) while eight studies reported expected outcomes so were at low risk of reporting bias.Eight studies evaluated therapy to prevent persistent kidney disease in HSP. There was no significant difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32), or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of HSP compared with placebo or supportive treatment. There were no significant differences in the risk of persistent kidney disease with antiplatelet therapy in children with or without kidney disease at entry. Heparin significantly reduced the risk of persistent kidney disease by three months compared with placebo (1 study, 228 children: RR 0.27, 95% CI 0.14 to 0.55); no significant bleeding occurred. Four studies examined the treatment of severe HSP-associated kidney disease. Two studies (one involving 56 children and the other involving 54 adults) compared cyclophosphamide with placebo or supportive treatment and found no significant benefit of cyclophosphamide. There were no significant differences in adverse effects. In one study comparing cyclosporin with methylprednisolone (15 children) there was no significant difference in remission at final follow-up at a mean of 6.3 years (RR 1.37, 95% CI 0.74 to 2.54). In one study (17 children) comparing mycophenolate mofetil with azathioprine, there was no significant difference in the remission of proteinuria at one year (RR 1.32, 95% CI 0.86 to 2.03). No studies were identified which evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of HSP.
AUTHORS' CONCLUSIONS
There are no substantial changes in conclusions from this update compared with the initial review. From generally low quality evidence, we found no evidence of benefit from RCTs for the use of prednisone or antiplatelet agents to prevent persistent kidney disease in children with HSP. Though heparin appeared effective, this potentially dangerous therapy is not justified to prevent serious kidney disease when fewer than 2% of children with HSP develop severe kidney disease. No evidence of benefit has been found for cyclophosphamide treatment in children or adults with HSP and severe kidney disease. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin and mycophenolate mofetil have any roles in the treatment of children with HSP and severe kidney disease.
Topics: Adrenal Cortex Hormones; Child; Child, Preschool; Cyclophosphamide; Humans; IgA Vasculitis; Immunosuppressive Agents; Kidney Diseases; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 26258874
DOI: 10.1002/14651858.CD005128.pub3 -
Frontiers in Neuroendocrinology Jan 2023Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of...
Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.
Topics: Humans; Contraceptive Agents; Neuroimaging; Brain; Electroencephalography
PubMed: 36577486
DOI: 10.1016/j.yfrne.2022.101051 -
Journal of Clinical Medicine Aug 2023Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO)... (Review)
Review
Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO) measures (PROMs) that are validated for other diseases. However, the validity evidence to support the use of existing PROMs in patients with TTP is unknown. In a systematic review of the literature, including studies of adults and children with TTP, we assessed the validity evidence for use of PROMs in clinical research and clinical practice, characterized HRQoL, described the integration of PROMs in clinical practice and evaluated PRO scores for patients with TTP compared with reference populations. From an initial 4518 studies, we identified 14 studies using 16 PROMs to assess general HRQoL domains in patients in remission. No identified studies assessed the validity of PROMs for the context of use of TTP and no studies described PROM integration into TTP clinical practice or evaluated PROMs that were specific for patients with TTP. Moreover, PRO scores were worse in patients with TTP compared with reference populations and other chronic conditions. We conclude that, in patients with TTP, PROMs pick up on important patient experiences not captured by clinical outcomes at present. There is, therefore, a need for studies that assess the validity of existing PROMs in patients with TTP to determine if TTP-specific PROMs specific to patients with TTP should be developed.
PubMed: 37568558
DOI: 10.3390/jcm12155155 -
F1000Research 2018The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and...
The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is "sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS". This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 - 18.01.2017, update 1. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.
Topics: Animals; Brain; Female; Fetus; Global Health; Guillain-Barre Syndrome; Humans; Nervous System Malformations; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 30631437
DOI: 10.12688/f1000research.13704.1