Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2 (PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs. METHODS: Tear samples were collected from 36 non-Sjögren syndrome dry eye patients (10 males and 26 females, mean age 50.11±11.17y). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time (TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay (ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction (MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores (R=0.608, P<0.001), however, they did not significantly associate with TBUT (R=0.153, P=0.373), Schirmer scores (R=-0.098, P=0.570), ocular surface staining scores (R=0.282, P=0.095), and stage of MGD (R=-0.107, P=0.535). Male sex was significantly negatively correlated with tear PGE2 levels. CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.     

Mean platelet volume and coronary artery disease: a systematic review and meta-analysis

Background

Platelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as an indicator of platelet reactivity. Thus, MPV may emerge as a potential marker of CAD risk. The aim of this study was to conduct a systematic review and meta-analysis comparing mean difference in MPV between patients with CAD and controls and pooling the odds ratio of CAD in those with high versus low MPV.

Methods

Medline and Scopus databases were searched up to 12 March 2013. All observational studies that considered MPV as a study's factor and measured CAD as an outcome were included. Two reviewers independently selected the studies and extracted the data.

Results

Forty studies were included in this meta-analysis. The MPV was significantly larger in patients with CAD than controls with the unstandardized mean difference of 0.70 fL (95% CI: 0.55, 0.85). The unstandardized mean difference of MPV in patients with acute coronary event and in patients with chronic stable angina was 0.84 fL (95% CI: 0.63, 1.04) and 0.46 fL (95% CI: 0.11, 0.81) respectively. Patients with larger MPV (≥ 7.3 fL) also had a greater odds of having CAD than patients with smaller MPV with a pooled odds ratio of 2.28 (95% CI: 1.46, 3.58).

Conclusion

Larger MPV was associated with CAD. Thus, it might be helpful in risk stratification, or improvement of risk prediction if combining it with other risk factors in risk prediction models.     

Lack of associations between thyroid function and obstructive sleep apnea severity in adults with prediabetes and diabetes mellitus

Sleep and Breathing - Hypothyroidism is associated with a high frequency of obstructive sleep apnea (OSA). However, the prevalence of OSA in hypothyroid patients is not different from the general...     

Risk prediction models of breast cancer: a systematic review of model performances

The number of risk prediction models has been increasingly developed, for estimating about breast cancer in individual women. However, those model performances are questionable. We therefore have conducted a study with the aim to systematically review previous risk prediction models. The results from this review help to identify the most reliable model and indicate the strengths and weaknesses of each model for guiding future model development. We searched MEDLINE (PubMed) from 1949 and EMBASE (Ovid) from 1974 until October 2010. Observational studies which constructed models using regression methods were selected. Information about model development and performance were extracted. Twenty-five out of 453 studies were eligible. Of these, 18 developed prediction models and 7 validated existing prediction models. Up to 13 variables were included in the models and sample sizes for each study ranged from 550 to 2,404,636. Internal validation was performed in four models, while five models had external validation. Gail and Rosner and Colditz models were the significant models which were subsequently modified by other scholars. Calibration performance of most models was fair to good (expected/observe ratio: 0.87–1.12), but discriminatory accuracy was poor to fair both in internal validation (concordance statistics: 0.53–0.66) and in external validation (concordance statistics: 0.56–0.63). Most models yielded relatively poor discrimination in both internal and external validation. This poor discriminatory accuracy of existing models might be because of a lack of knowledge about risk factors, heterogeneous subtypes of breast cancer, and different distributions of risk factors across populations. In addition the concordance statistic itself is insensitive to measure the improvement of discrimination. Therefore, the new method such as net reclassification index should be considered to evaluate the improvement of the performance of a new develop model.     

Cartoon versus traditional self-study handouts for medical students: CARTOON randomized controlled trial

Objective: The objective of this study is to compare the effectiveness of a “cartoon-style” handout with a “traditional-style” handout in a self-study assignment for preclinical medical students.

Methods: Third-year medical students (n?=?93) at the Faculty of Medicine Ramathibodi Hospital, Mahidol University, took a pre-learning assessment of their knowledge of intercostal chest drainage. They were then randomly allocated to receive either a “cartoon-style” or a “traditional-style” handout on the same topic. After studying these over a 2-week period, students completed a post-learning assessment and estimated their levels of reading completion.

Results: Of the 79 participants completing the post-learning test, those in the cartoon-style group achieved a score 13.8% higher than the traditional-style group (p?=?0.018). A higher proportion of students in the cartoon-style group reported reading ≥75% of the handout content (70.7% versus 42.1%). In post-hoc analyses, students whose cumulative grade point averages (GPA) from previous academic assessments were in the middle and lower range achieved higher scores with the cartoon-style handout than with the traditional one. In the lower-GPA group, the use of a cartoon-style handout was independently associated with a higher score.

Conclusions: Students given a cartoon-style handout reported reading more of the material and achieved higher post-learning test scores than students given a traditional handout.     

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome

Study Type – Therapy (systematic review) Level of Evidence 1a What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti‐inflammatories and α‐blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta‐analysis of current evidence from all available randomized placebo‐controlled trials with similar inclusion criteria and outcome measures shows that these ‘3‐As’ of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti‐inflammatories and α‐blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals.

OBJECTIVES

• ? To provide an updated network meta‐analysis mapping α‐blockers, antibiotics and anti‐inflammatories (the 3‐As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
• ? To use the results of this meta‐analysis to comment on the role of the 3‐As in clinical practice.

PATIENTS AND METHODS

• ? We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH‐CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients.
• ? A longitudinal mixed regression model (network meta‐analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α‐blockers, antibiotics, anti‐inflammatory/immune modulation therapies, α‐blockers plus antibiotics, and placebo).

RESULTS

• ? Nineteen studies (1669 subjects) were eligible for analysis.
• ? α‐blockers, antibiotics and anti‐inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of ?10.8 (95% CI ?13.2 to ?8.3; P < 0.001), ?9.7 (95% CI ?14.2 to ?5.3; P < 0.001) and ?1.7 (95% CI ?3.2 to ?0.2; P= 0.032) respectively, while α‐blockers plus antibiotics resulted in the greatest CPSI difference (?13.6, 95% CI ?16.7 to ?10.6; P < 0.001).
• ? With respect to responder analysis compared with placebo, anti‐inflammatories showed the greatest response rates (risk ratio 1.7, 95% CI 1.4–2.1; P < 0.001) followed by α‐blockers (risk ratio 1.4, 95% CI 1.1–1.8; P= 0.013) and antibiotics (risk ratio 1.2, 95% CI 0.7–1.9; P= 0.527).

CONCLUSIONS

• ? α‐blockers, antibiotics and/or anti‐inflammatory/immune modulation therapy appear to be beneficial for some patients with CP/CPPS.
• ? The magnitude of effect and the disconnect between mean CPSI decrease and response rates compared with placebo suggest that directed multimodal therapy, rather than mono‐therapy, with these agents should be considered for optimal management of CP/CPPS.

     

Comparative efficacy of bevacizumab,ranibizumab, and aflibercept for treatment of macular edema secondary to retinal vein occlusion: a systematic review and network meta-analysis

Introduction: Anti-vascular endothelial growth factor (VEGF) therapy has become the most commonly used treatment for macular edema secondary to retinal vein occlusion (RVO). Although its superior efficacy as compared to other interventions has been proven, there is a lack of evidence for relative efficacy among anti-VEGF drugs.

Areas covered: This work systematically reviewed and compared the efficacy of intravitreal bevacizumab, ranibizumab, and aflibercept for treating macular edema due to RVO. PubMed, EMBASE, and the Cochrane Library were searched from their inception until October 2017. Eleven randomized controlled trials (18 articles; 1830 adult patients) were identified. The proportion of patients who gained at least 15 letters in best-corrected visual acuity (BCVA), mean change from baseline in BCVA, and mean change from baseline in central macular thickness (CMT) were reported and these efficacy outcomes at 6 months were analyzed in network meta-analysis.

Expert commentary: Apparently, bevacizumab, ranibizumab, and aflibercept were significantly superior to sham injection in terms of BCVA improvement and CMT reduction and had good safety profiles. However, there were no statistically significant differences in any outcomes among anti-VEGF drugs. In selecting an anti-VEGF drug for individual patients, other factors including affordability, drug availability, and patient characteristics should be considered.     

The association between cytokine gene polymorphisms and graft rejection in liver transplantation: A systematic review and meta-analysis

We investigated the contribution of polymorphisms in cytokine genes (TNFa-308, IL10-1082 and -592, TGFb1-c10 and c25, and IFNg + 874) on the risk of graft rejection in liver transplantation. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. In total, 12 studies were eligible and included in the study. Data extraction and assessments for risk of bias were independently performed by two reviewers. Data for allele frequencies, allelic, and genotypic effects were pooled. Heterogeneity and publication bias were assessed. Pooled minor allele frequencies for TNFa-308, IL10-1082, TGFb1-c10, TGFb1-c25, IFNg + 874, and IL10-592 were 0.140 (95% CI: 0.083, 0.198), 0.432 (95% CI: 0.392, 0.472), 0.387 (95% CI: 0.307, 0.467), 0.090 (95% CI: 0.056, 0.123), 0.460 (95% CI: 0.392, 0.528), and 0.224 (95% CI: 0.178, 0.269), respectively. OnlyTNFa-308 and IL10-1082 polymorphisms were significantly associated with graft rejection. Patients who carried minor homozygous genotypes for these two polymorphisms were at 3.5 and 1.69 times higher risk of graft rejections than patients who carried major homozygous genotypes. The estimated lambdas were 0.41 and 0.47, suggesting an additive mode of effect was most likely. However, we could not detect the associations of TGFb1at c10 and c25, INFg + 874, and IL10-592 polymorphisms and graft rejection. In summary, our systematic review has demonstrated that TNFa-308 and IL10-1082 are potential risk factors of poor outcomes in liver transplantation. Future updated meta-analysis studies to confirm the power of these genotypes in association with allograft rejection are needed.