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Journal of Clinical Medicine Mar 2019The 1858T allele in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) locus shows one of the strongest and most consistent genetic associations with...
The 1858T allele in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) locus shows one of the strongest and most consistent genetic associations with autoimmune diseases. We synthesized all meta-analyses reporting a genetic association of the PTPN22 1858T C/T polymorphism with autoimmune diseases. This work examined their validity to discover false positive results under Bayesian methods. We conducted a PubMed search to identify relevant publications and extracted the respective results, published until 30 November 2018. In observational studies, the associations of 1858 C/T genetic variant were noteworthy for 12 autoimmune or autoimmunity-related diseases (rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, juvenile idiopathic arthritis, Crohn's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, vitiligo, Graves' disease, myasthenia gravis, Addison's disease, giant cell arteritis, and endometriosis). In contrast, we could not confirm the noteworthiness for eight diseases (systemic sclerosis, psoriasis, Behçet's disease, autoimmune thyroid disease, alopecia areata, Sjögren's syndrome, inflammatory bowel disease, and ankylosing spondylitis). From the meta-analysis of genome-wide association studies (GWAS) with a -value < 5 × 10, findings verified noteworthiness for all autoimmune diseases (psoriatic arthritis, myasthenia gravis, juvenile idiopathic arthritis and rheumatoid arthritis). The results from meta-analysis of GWAS showing a -value ranging between 0.05 and 5 × 10 were noteworthy under both Bayesian approaches (ANCA-associated vasculitis, type 1 diabetes mellitus, giant cell arteritis and juvenile idiopathic arthritis). Re-analysis of observational studies and GWAS by Bayesian approaches revealed the noteworthiness of all significant associations observed by GWAS, but noteworthiness could not be confirmed for all associations found in observational studies.
PubMed: 30871019
DOI: 10.3390/jcm8030347 -
Hormone and Metabolic Research =... Mar 2019Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced... (Meta-Analysis)
Meta-Analysis
Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9-8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2-1.2) and pembrolizumab (1.1%; 95% CI, 0.5-2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction - particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4-9.8; pembrolizumab, 8.5%; 95% CI, 7.5-9.7; PD-L1, 5.5%; 95% CI, 4.4-6.8; ipilimumab, 3.8%; 95% CI, 2.6-5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2-16.4%), hyperthyroidism (9.4-10.4%), hypophysitis (8.8-10.5%), and primary adrenal insufficiency (5.2-7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.
Topics: Addison Disease; Antineoplastic Agents, Immunological; Diabetes Mellitus; Humans; Hypophysitis; Neoplasms; Thyroid Diseases
PubMed: 30861560
DOI: 10.1055/a-0843-3366 -
Addiction (Abingdon, England) Jan 2019There is limited evidence on what shapes amphetamine-type stimulant (ATS) use trajectories. This systematic narrative review and qualitative synthesis aimed to identify...
Which individual, social and environmental influences shape key phases in the amphetamine type stimulant use trajectory? A systematic narrative review and thematic synthesis of the qualitative literature.
BACKGROUND AND AIMS
There is limited evidence on what shapes amphetamine-type stimulant (ATS) use trajectories. This systematic narrative review and qualitative synthesis aimed to identify individual, social and environmental influences shaping key phases in the ATS use trajectory: initiation, continuation, increase/relapse and decrease/abstinence.
METHODS
MEDLINE, PsycINFO, EMBASE, and PROQUEST (social science premium collection) were searched from 2000 to 2018. Studies of any qualitative design were eligible for inclusion. Extracted data were analysed according to four key phases within drug pathways, and then cross-analysed for individual, social and environmental influences.
RESULTS
Forty-four papers based on 39 unique studies were included, reporting the views of 1879 ATS users. Participants were aged 14-58 years, from varied socio-economic and demographic groups, and located in North America, Europe, Australasia and South East Asia. Reasons for initiation included: to boost performance at work and in sexual relationships, promote a sense of social 'belonging' and help manage stress. Similar reasons motivated continued use, combined with the challenge of managing withdrawal effects in long-term users. Increased tolerance and/or experiencing a critical life event contributed to an increase in use. Reasons for decrease focused on: increased awareness of the negative health impacts of long-term use, disconnecting from social networks or relationships and financial instability.
CONCLUSIONS
Amphetamine-type stimulant users are a highly diverse population, and their drug use careers are shaped by a complex dynamic of individual, social and environmental factors. Tailored, joined-up interventions are needed to address users' overlapping economic, health and social care needs in order to support long-term abstinence.
Topics: Amphetamine-Related Disorders; Disease Progression; Humans; Methamphetamine; Motivation; N-Methyl-3,4-methylenedioxyamphetamine; Peer Group; Qualitative Research; Risk Factors; Sexual Behavior; Social Behavior; Social Environment
PubMed: 30176077
DOI: 10.1111/add.14434 -
Clinical Endocrinology Aug 2018Evaluating the patient with adrenal disease is challenging due to the lack of precise clinical and biochemical parameters for disease control. Quality of life (QOL)... (Review)
Review
BACKGROUND
Evaluating the patient with adrenal disease is challenging due to the lack of precise clinical and biochemical parameters for disease control. Quality of life (QOL) evaluation aims to measure the patient's subjective experience.
OBJECTIVE
To describe how QOL is defined and measured in adrenal disease, critically appraise the use of QOL tools in published literature, discuss the implications of these findings and provide direction for further research in this field.
MATERIALS AND METHODS
We searched the Cochrane library, EMBASE, Google Scholar, PsycINFO, PubMed, Web of Science databases to identify only primary studies where self-reported QOL was measured as a parameter in adults with confirmed adrenal disease, and results presented in English. Key data were independently extracted from each study and adherence to reporting guidelines evaluated.
RESULTS
A total of 117 studies involving 13 717 subjects were included. The vast majority of studies did not define QOL. The most common approach was to combine generic and domain-specific tools, although disease-specific tools are increasingly being used. Adherence to reporting guidelines was variable. A narrative synthesis of the findings was performed.
CONCLUSION
We present the first systematic review of QOL in adrenal disease. Quality of life is reduced in patients with adrenal disease, irrespective of adrenal hyperfunction or hypofunction. Quality of life improved with therapy but was not completely reversed despite biochemical remission. Authors should adhere to consistent reporting practices which are interpretable by clinicians. Further research is required to explain the mechanisms driving impaired QOL and value of QOL evaluations in the clinical context.
PubMed: 29672878
DOI: 10.1111/cen.13719 -
The Journal of Antimicrobial... Feb 2018Antibiotic use can have negative unintended consequences including disruption of the human microbiota, which is thought to protect against pathogen overgrowth. We...
BACKGROUND
Antibiotic use can have negative unintended consequences including disruption of the human microbiota, which is thought to protect against pathogen overgrowth. We conducted a systematic review to assess whether there is an association between exposure to antibiotics and subsequent risk of community-acquired infections.
METHODS
We searched MEDLINE, EMBASE and Web of Science for studies published before 30 June 2017, examining the association between antibiotic use and subsequent community-acquired infection. Infections caused by Clostridium difficile and fungal organisms were excluded. Studies focusing exclusively on resistant organism infections were also excluded.
RESULTS
Eighteen of 22588 retrieved studies met the inclusion criteria. From these, 16 studies reported a statistically significant association between antibiotic exposure and subsequent risk of community-acquired infection. Infections associated with prior antibiotic use included Campylobacter jejuni infection (one study), recurrent furunculosis (one study), invasive Haemophilus influenzae type b infection (one study), infectious mastitis (one study), meningitis (one study), invasive pneumococcal disease (one study), Staphylococcus aureus skin infection (one study), typhoid fever (two studies), recurrent boils and abscesses (one study), upper respiratory tract infection and urinary tract infection (one study) and Salmonella infection (five studies), although in three studies on Salmonella infection the effect was of marginal statistical significance.
CONCLUSIONS
We found an association between prior antibiotic use and subsequent risk of a diverse range of community-acquired infections. Gastrointestinal and skin and soft tissue infections were most frequently found to be associated with prior antibiotic exposure. Our findings support the hypothesis that antibiotic use may predispose to future infection risk, including infections caused by both antibiotic-resistant and non-resistant organisms.
Topics: Anti-Bacterial Agents; Bacterial Infections; Community-Acquired Infections; Drug Utilization; Humans; Risk Assessment; Risk Factors
PubMed: 29149266
DOI: 10.1093/jac/dkx374 -
PLoS Medicine Sep 2017Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension.
METHODS AND FINDINGS
Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies.
CONCLUSIONS
Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Life Style; Patient Education as Topic; Randomized Controlled Trials as Topic
PubMed: 28926573
DOI: 10.1371/journal.pmed.1002389 -
The Cochrane Database of Systematic... Feb 2017Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian... (Review)
Review
BACKGROUND
Blepharokeratoconjunctivitis (BKC) is a type of inflammation of the surface of the eye and eyelids that involves changes of the eyelids, dysfunction of the meibomian glands, and inflammation of the conjunctiva and cornea. Chronic inflammation of the cornea can lead to scarring, vascularisation and opacity. BKC in children can cause significant symptoms including irritation, watering, photophobia and loss of vision from corneal opacity, refractive error or amblyopia.Treatment of BKC is directed towards modification of meibomian gland disease and the bacterial flora of lid margin and conjunctiva, and control of ocular surface inflammation. Although both topical and systemic treatments are used to treat people with BKC, this Cochrane review focuses on topical treatments.
OBJECTIVES
To assess and compare data on the efficacy and safety of topical treatments (including antibiotics, steroids, immunosuppressants and lubricants), alone or in combination, for BKC in children from birth to 16 years.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE ( January 1946 to 11 July 2016), Embase (January 1980 to 11 July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 July 2016. We searched the reference lists of identified reports and the Science Citation Index to identify any additional reports of studies that met the inclusion criteria.
SELECTION CRITERIA
We searched for randomised controlled trials that involved topical treatments in children up to 16 years of age with a clinical diagnosis of BKC. We planned to include studies that evaluated a single topical medication versus placebo, a combination of treatments versus placebo, and those that compared two or multiple active treatments. We planned to include studies in which participants received additional treatments, such as oral antibiotics, oral anti-inflammatories, warm lid compresses and lid margin cleaning.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of the literature search (titles and abstracts) to identify studies that met the inclusion criteria of the review and applied standards as expected for Cochrane reviews. We graded the certainty of the evidence using GRADE.
MAIN RESULTS
We included one study from the USA that met the inclusion criteria. In the study, 137 children aged zero to six years old with blepharoconjunctivitis were randomised to treatment in one of four trial arms (loteprednol etabonate/tobramycin combination, loteprednol etabonate alone, tobramycin alone or placebo) for 15 days, with assessments on days 1, 3, 7 and 15. We judged the study to be at high risk of attrition bias and bias due to selective outcome reporting. The study did not report the number of children with improvement in symptoms nor with total or partial success as measured by changes in clinical symptoms.All children showed a reduction in blepharoconjunctivitis grade score, but there was no evidence of important differences between groups. Visual acuity was not fully reported but the authors stated that there was no change in visual acuity in any of the treatment groups. The study reported ocular and non ocular adverse events but was underpowered to detect differences between the groups. Ocular adverse events were as follows: loteprednol/tobramycin 1/34 (eye pain); loteprednol 4/35 (eye pain, conjunctivitis, eye discharge, eye inflammation); tobramycin 0/34; placebo (vehicle) 0/34. The evidence was limited for all these outcomes and we judged it to be very low certainty.There was no information on clinical signs (aside from grade score), disease progression or quality of life.
AUTHORS' CONCLUSIONS
There is no high-quality evidence of the safety and efficacy of topical treatments for BKC, which resulted in uncertainty about the indications and effectiveness of topical treatment. Clinical trials are required to test efficacy and safety of current and any future treatments. Outcome measures need to be developed which can capture both objective clinical and patient-reported aspects of the condition and treatments.
Topics: Administration, Topical; Anti-Allergic Agents; Anti-Bacterial Agents; Blepharitis; Child; Child, Preschool; Conjunctiva; Eyelids; Humans; Infant; Infant, Newborn; Keratoconjunctivitis; Loteprednol Etabonate; Randomized Controlled Trials as Topic; Tobramycin
PubMed: 28170093
DOI: 10.1002/14651858.CD011965.pub2 -
Advances in Nutrition (Bethesda, Md.) Jul 2016Strategic translational research is designed to address research gaps that answer specific guidance questions. It provides translational value with respect to nutrition... (Review)
Review
Strategic translational research is designed to address research gaps that answer specific guidance questions. It provides translational value with respect to nutrition guidance and regulatory and public policy. The relevance and the quality of evidence both matter in translational research. For example, design decisions regarding population, intervention, comparator, and outcome criteria affect whether or not high-quality studies are considered relevant to specific guidance questions and are therefore included as evidence within the context of systematic review frameworks used by authoritative food and health organizations. The process used in systematic reviews, developed by the USDA for its Nutrition Evidence Library, is described. An eating pattern and cardiovascular disease (CVD) evidence review is provided as an example, and factors that differentiated the studies considered relevant and included in that evidence base from those that were excluded are noted. Case studies on ω-3 (n-3) fatty acids (FAs) and industrial trans-FAs illustrate key factors vital to relevance and translational impact, including choice of a relevant population (e.g., healthy, at risk, or diseased subjects; general population or high-performance soldiers); dose and form of the intervention (e.g., food or supplement); use of relevant comparators (e.g., technically feasible and realistic); and measures for both exposure and outcomes (e.g., inflammatory markers or CVD endpoints). Specific recommendations are provided to help increase the impact of nutrition research on future dietary guidance, policy, and regulatory issues, particularly in the area of lipids.
Topics: Cardiovascular Diseases; Diet; Evidence-Based Medicine; Fatty Acids, Omega-3; Feeding Behavior; Humans; Nutritional Sciences; Recommended Dietary Allowances; Research Design; Review Literature as Topic; Trans Fatty Acids; Translational Research, Biomedical; United States; United States Department of Agriculture
PubMed: 27422509
DOI: 10.3945/an.115.010926 -
Digestive Diseases and Sciences Sep 2016Intragastric balloons (IGBs) are safe and effective in inducing weight loss in obese patients. The objective of this study was to review and analyze the available data... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intragastric balloons (IGBs) are safe and effective in inducing weight loss in obese patients. The objective of this study was to review and analyze the available data of the effect of IGB on markers of nonalcoholic fatty liver disease (NAFLD) and liver enzymes.
METHODS
Searches were performed of MEDLINE and Embase databases from inception through January 2016. Study inclusion criteria were the following: ≥5 overweight or obese adult patients undergoing intragastric balloon placement, with liver tests [alanine aminotransferase (ALT) or gamma-glutamyl transpeptidase (GGT)] or markers of NAFLD (e.g., imaging, biopsy) reported before balloon insertion and after balloon removal at 6 months.
RESULTS
Nine observational studies and one randomized trial were identified. ALT decreased by -10.02 U/l (95 % CI, -13.2, -6.8), GGT decreased by -9.82 U/l (95 % CI, -12.9, -6.8), and BMI decreased by -4.98 kg/m(2) (-5.6, -4.4) with IGB therapy. Hepatic steatosis improved from baseline after 6 months of balloon therapy by magnetic resonance imaging (fat fraction, 16.7 ± 10.9-7.6 ± 9.8, p = 0.003), ultrasound (severe liver steatosis, 52-4 %, p < 0.0001). Histological NAFLD activity score was lower after 6 months of IGB versus control with sham endoscopy and diet (2 ± 0.75 vs. 4 ± 2.25, p = 0.03).
CONCLUSION
The use of intragastric balloon decreases liver enzymes and is potentially an effective short-term treatment for NAFLD as part of a multidisciplinary approach. Larger, more rigorous trials are needed to confirm the effect of IGBs on NAFLD.
Topics: Alanine Transaminase; Bariatric Surgery; Gastric Balloon; Humans; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Treatment Outcome; Ultrasonography; Weight Loss; gamma-Glutamyltransferase
PubMed: 27207181
DOI: 10.1007/s10620-016-4178-2 -
Journal of Neurologic Physical Therapy... Mar 2009Parkinson's disease is a progressive neurodegenerative disorder that affects neurophysiologic function, movement abilities, and quality of life (QOL). Research examining... (Review)
Review
BACKGROUND AND PURPOSE
Parkinson's disease is a progressive neurodegenerative disorder that affects neurophysiologic function, movement abilities, and quality of life (QOL). Research examining the effects of exercise has suggested benefits related to a variety of outcomes; however, no reviews have synthesized research findings across the spectrum of disability. This project sought to systematically review studies that examined the impact of exercise interventions on balance outcomes for people with Parkinson's disease, within the categories defined by the World Health Organization in the International Classification of Functioning, Disability, and Health (ICF) model.
METHODS
A systematic review of medical literature databases was performed using keywords Parkinson's disease and exercise. Studies were eligible if the intervention included exercise and examined variables within one of the three ICF categories. Following the ICF model, outcomes regarding Body Structure and Function, Activity, and Participation were measured, respectively, in terms of postural instability, balance task performance, and QOL and fall events.
RESULTS
Within the Body Structure and Function category, there was moderate evidence that exercise resulted in improvements in postural instability. Within the Activity category, there was moderate evidence that exercise was effective for improving balance task performance. In contrast, within the Participation category, there was limited evidence that exercise resulted in improvements in QOL measures or fall events.
DISCUSSION AND CONCLUSIONS
Regardless of the strength of the evidence, the studies reviewed all report that exercise resulted in improvements in postural stability and balance task performance. Despite these improvements, the number and quality of the studies and the outcomes used were limited. There is a need for longer term follow-up to establish trajectory of change and to determine if any gains are retained long term. The optimal delivery and content of exercise interventions (dosing, component exercises) at different stages of the disease are not clear.
Topics: Exercise Therapy; Humans; Motor Activity; Neuropsychological Tests; Parkinson Disease; Postural Balance; Psychomotor Performance; Quality of Life; Treatment Outcome
PubMed: 19265767
DOI: 10.1097/NPT.0b013e3181990fcc