METHOD: A systematic Boolean search in PubMed, EMBase and EBSCOhost research databases was performed. Keyword search and citation analysis were also conducted. Empirical studies reporting ICT based interventions, and their implications on relative effectiveness in reducing unnecessary diagnostic tests (pathology tests or medical imaging) were evaluated independently by two reviewers based on a rigorously developed coding protocol.
RESULTS: 92 research articles from peer-reviewed journals were identified as eligible. 47 studies involved a single-method intervention and 45 involved multi-method interventions. Regardless of the number of interventions involved in the studies, ICT-based interventions were utilized by 71 studies and 59 of them were shown to be effective in reducing unnecessary testing. A clinical decision support (CDS) tool appeared to be the most adopted ICT approach, with 46 out of 71 studies using CDS tools. The CDS tool showed effectiveness in reducing test volume in 38 studies and reducing cost in 24 studies.
CONCLUSIONS: This review investigated five frequently utilized intervention methods, ICT-based, education, introduction of guidelines or protocols, audit and feedback, and reward and punishment. It provides in-depth analysis of the efficacy of different types of interventions and sheds insights about the benefits of ICT based interventions, especially those utilising CDS tools, to reduce unnecessary diagnostic testing. The replicability of the studies is limited due to the heterogeneity of the studies in terms of context, study design, and targeted types of tests.
OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety.
SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment.
DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading.
MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia.
AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.
METHODS: Ten subjects (n = 10) who had upper and lower fixed appliances (MBT, 3 M Unitek, 0.022″ × 0.028″) were recruited for this study. Human gingival crevicular fluid (GCF) was obtained using periopaper strips at pre-treatment (T0), 1 month (T1), 3 months (T3), and 6 months (T6) of orthodontic treatment. Periapical radiographs of the upper permanent central incisors were taken at T0 and T6 to measure the amount of root resorption. Identification of changes in PA was performed using liquid chromatography-tandem mass spectrometry. Student's t-test was then performed to determine the significance of the differences in protein abundance before and after orthodontic treatment.
RESULTS: Our findings showed that all ten subjects had mild root resorption, with an average resorption length of 0.56 ± 0.30 mm. A total of 186 proteins were found to be commonly present at T0, T1, T3, and T6. There were significant changes in the abundance of 16 proteins (student's t-test, p ≤ 0.05). The increased PA of S100A9, immunoglobulin J chain, heat shock protein 1A, immunoglobulin heavy variable 4-34 and vitronectin at T1 suggested a response to stress that involved inflammation during the early phase of orthodontic treatment. On the other hand, the increased PA of thymidine phosphorylase at T3 suggested growth promotion and, angiogenic and chemotactic activities.
CONCLUSIONS: The identified proteins can be potential early markers for root resorption based on the increase in their respective PA and predicted roles during the early phase of orthodontic treatment. Non-invasive detection of root resorption using protein markers as early as possible is extremely important as it can aid orthodontists in successful orthodontic treatment.
METHODS: A cross-sectional study was carried out on medical students in a public medical school. DASS-21, the neuroticism-subscale of USMaP-i and SAS-SV were administered to measure psychological distress, neuroticism, and smartphone addiction of the medical students. Spearman correlation was performed to examine the correlation between smartphone addiction with psychological distress and neuroticism. Simple linear regression was performed to investigate relationship factors of smartphone addiction.
RESULTS: A total of 574 medical students participated in this study. The prevalence of smartphone addiction was 40.6%. It was higher among male (49.2%) compared to female (36.6%) medical students. The result showed a fair positive correlation between smartphone addiction and psychological health (rdepression = 0.277, p-value
METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.
RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.
CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.
METHODS: We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors.
RESULTS: A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB.
DISCUSSION: Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.