Mazen Ferwana

Pioglitazone and risk of bladder cancer: A meta-analysis of controlled studies

Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta‐analysis to evaluate the magnitude of this association and the quality of the supporting evidence.

Accuracy of urea breath test in Helicobacter pylori infection: Meta-analysis

AIM To quantitatively summarize and appraise the available evidence of urea breath test (UBT) use to diagnose Helicobacter pylori (H. pylori) infection in patients with dyspepsia and provide pooled diagnostic accuracy measures. METHODS We searched MEDLINE, EMBASE, Cochrane library and other databases for studies addressing the value of UBT in the diagnosis of H. pylori infection. We included cross-sectional studies that evaluated the diagnostic accuracy of UBT in adult patients with dyspeptic symptoms. Risk of bias was assessed using QUADAS (Quality Assessment of Diagnostic Accuracy Studies)-2 tool. Diagnostic accuracy measures were pooled using the random-effects model. Subgroup analysis was conducted by UBT type (13C vs 14C) and by measurement technique (Infrared spectrometry vs Isotope Ratio Mass Spectrometry). RESULTS Out of 1380 studies identified, only 23 met the eligibility criteria. Fourteen studies (61%) evaluated 13C UBT and 9 studies (39%) evaluated 14C UBT. There was significant variation in the type of reference standard tests used across studies.Pooled sensitivity was 0.96 (95%CI: 0.95-0.97) andpooled specificity was 0.93 (95%CI: 0.91-0.94). Likelihood ratio for a positive test was 12 and for a negative test was 0.05 with an area under thecurve of 0.985. Meta-analyses were associated with a significant statistical heterogeneity that remained unexplained after subgroup analysis. The included studies had a moderate risk of bias. CONCLUSION UBT has high diagnostic accuracy for detecting H. pylori infection in patients with dyspepsia. The reliability of diagnostic meta-analytic estimates however is limited by significant heterogeneity.

Development of a Novel, Multilayered Presentation Format for Clinical Practice Guidelines

BACKGROUND Bridging the gap between clinical research and everyday health-care practice requires effective communication strategies. To address current shortcomings in conveying practice recommendations and supporting evidence, we are creating and testing presentation formats for clinical practice guidelines (CPGs). METHODS We carried out multiple cycles of brainstorming and sketching, developing a prototype. Physicians participating in the user testing viewed CPG formats linked to clinical scenarios and engaged in semistructured interviews applying a think-aloud method for exploring important aspects of user experience. RESULTS We developed a multilayered presentation format that allows clinicians to successively view more in-depth information. Starting with the recommendations, clinicians can, on demand, access a rationale and a key information section containing statements on quality of the evidence, balance between desirable and undesirable consequences, values and preferences, and resource considerations. We collected feedback from 27 stakeholders and performed user testing with 47 practicing physicians from six countries. Advisory group feedback and user testing of the first version revealed problems with conceptual understanding of underlying CPG methodology, as well as difficulties with the complexity of the layout and content. Extensive revisions made before the second round of user testing resulted in most participants expressing overall satisfaction with the final presentation format. CONCLUSIONS We have developed an electronic, multilayered, CPG format that enhances the usability of CPGs for frontline clinicians. We have implemented the format in electronic guideline tools that guideline organizations can now use when authoring and publishing their guidelines.

Erlotinib in wild type epidermal growth factor receptor non‑small cell lung cancer: A systematic review

BACKGROUND: Targeting epidermal growth factor receptors (EGFR) is an innovative approach to managing non-small cell lung cancer (NSCLC) which harbors EGFR mutation. However, the efficacy of these agents like erlotinib in patients without the mutation is not known. METHODS: This systematic review included Phase III randomized clinical trials that compared single agent erlotinib to other management options in the setting of NSCLC with reported outcome data on patients with EGFR wild type (EGFRWT) tumors. Outcome data include overall survival (OS), progression free survival (PFS) and response rate (RR). Random effects meta-analysis was used to pool outcomes across studies. RESULTS: Three studies met the inclusion criteria. These studies included a total of 2044 patients with outcome data on 674 patients with EGFRWT tumors (33%). Meta-analysis revealed a statistically significant improvement in OS with erlotinib (hazard ratio of 0.780; 95% confidence interval: 0.654-0.930, P = 0.006). Data were not available to perform PFS or RR analysis. The quality of this evidence is considered to be moderate to high. CONCLUSION: Our study revealed a significant benefit of erlotinib in patient with EGFRWT tumors compared with other approaches. These findings add another therapeutic option to patients generally considered difficult to treat.

Nephrotic syndrome after treatment of Crohn's disease with mesalamine: Case report and literature review

Inflammatory bowel disease and its various treatments may affect the kidney in several ways. Recently, case reports have been published documenting the development of nephrotic syndrome after the treatment for inflammatory bowel disease with 5-aminosalicylic acid derivatives. We report a 50-year-old patient who was diagnosed with Crohns disease and was treated with mesalamine. The patient subsequently developed nephrotic syndrome and a renal biopsy showed minimal change disease. He was treated with losartan and rosuvastatin and showed improvement in his renal function and serum cholesterol level. This is the first reported case in Crohns disease although there have been six previous case reports of nephrotic syndrome following salicylic acid derivatives for ulcerative colitis.

Tissue plasminogen activator versus heparin for locking dialysis catheters: A systematic review.

Background and Objectives: Hemodialysis catheters are commonly used when renal replacement therapy is initiated. These catheters have significant complications. Among “locking” solutions used in an attempt to decrease these complications is recombinant tissue plasminogen activator (rt-PA). This systematic review is to determine the efficacy of rt-PA versus heparin, the standard of care. Materials and Methods: A systematic review of randomized controlled trials studying rt-PA alone or rt-PA plus heparin versus heparin alone as locking agents for hemodialysis catheters, which included patients needed a temporary hemodialysis catheter for hemodialysis. We identified relevant trials through electronic databases and correspondence with experts. Two investigators independently reviewed potentially eligible trials and extracted data. Results: Three trials met the inclusion criteria. One trial reported an improved catheter malfunctioning in patients using rt-PA plus heparin to lock catheters (20.0%) versus heparin alone (34.8%). Another trial reported higher blood flow rate in hemodialysis catheters in patients who received rt-PA (231.6 ± 12.4 mL/min) compared with those who received heparin (206.9 mL/min). The third trial reported formation and weight of clots which were decreased by half in rt-PA group versus heparin group. Conclusions: In the few randomized trials that met our inclusion criteria, the use of rt-PA as a locking solution for hemodialysis catheters seems to be associated with fewer adverse events and catheter malfunctioning as compared with heparin. Our systematic review is limited by the few randomized trials addressing our question and the wide variety of outcome measures. Further prospective randomized trials are needed to confirm this conclusion.

Integration of Evidence Based Medicine into a Medical Curriculum

The College of Medicine at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) was established in January 2004. The four-year curriculum was based on the Problem Based Learning (PBL) format and involved the web-based graduate medical program adopted from the University of Sydney, Australia. At KSAU-HS, one additional semester was added to the beginning of this curriculum to prepare the students in English language skills, PBL, Information Technology and Evidence Based Medicine (EBM). EBM is part of the Personal and Professional Development (PPD) theme of the medical curriculum and is integrated into each stage of the medical curriculum. These modifications of the University of Sydney curriculum are presented here as a model of EBM integration into a college of medicine curriculum.

Integration of evidence based medicine into the clinical years of a medical curriculum

Teaching Evidence Based Medicine (EBM) helps medical students to develop their decision making skills based on current best evidence, especially when it is taught in a clinical context. Few medical schools integrate Evidence Based Medicine into undergraduate curriculum, and those who do so, do it at the academic years only as a standalone (classroom) teaching but not at the clinical years. The College of Medicine at King Saud bin Abdulaziz University for Health Sciences was established in January 2004. The college adopted a four-year Problem Based Learning web-based curriculum. The objective of this paper is to present our experience in the integration of the EBM in the clinical phase of the medical curriculum. We teach EBM in 3 steps: first step is teaching EBM concepts and principles, second is teaching the appraisal and search skills, and the last step is teaching it in clinical rotations. Teaching EBM at clinical years consists of 4 student-centered tutorials. In conclusion, EBM may be taught in a systematic, patient centered approach at clinical rounds. This paper could serve as a model of Evidence Based Medicine integration into the clinical phase of a medical curriculum.

Open versus endovascular stent graft repair of abdominal aortic aneurysms: do we need more randomized clinical trials?

We performed an analysis to assess the need for conducting additional randomized controlled trials (RCTs) comparing open and endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Trial sequential analysis (TSA) is a statistical methodology that can calculate the required information size of a meta-analysis and assess the risk of random errors similar to interim analysis in a single optimally powered trial. It helps to decide whether we have obtained sufficient evidence or whether further RCTs are required. For short-term mortality reintervention rates, TSA showed firm evidence that there would be no extra benefit in conducting more RCTs to detect the effectiveness of EVAR versus open repair. For long-term mortality, TSA revealed either inconclusive evidence to support or refute endovascular or open repair; so, further RCTs should be performed to investigate long-term, all-cause mortality after AAA repair.

Age and BMI Adjusted Comparison of Reproductive Hormones in PCOS.

Objective and Background: Polycystic ovary syndrome (PCOS) is a complex condition and has been described in women who have polycystic ovaries as the underlying cause of hirsutism and chronic anovulation. Studies on PCOS in the Saudi population are very few. The aim of this study was to investigate the reproductive hormones levels in patients with PCOS. Effect of age and body mass index (BMI) on the hormonal findings was eliminated through a multivariate analysis. Materials and Methods: A comparative study was conducted on Saudi subjects attending the outpatient clinic of National Guard Hospital in Riyadh. A total of 62 cases with PCOS and 40 healthy Saudi women were included in this study. Physical evaluation and laboratory investigations were carried out. Blood luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-SO4), sex hormone-binding globulin (SHBG), total testosterone, prolactin, and progesterone were determined. To adjust for the potentially confounding effect of age and BMI, we carried out multivariate linear regression analyses for the association between each of the reproductive hormones and PCOS. Results: Serum levels of FSH, SHBG, and progesterone were significantly lower in PCOS compared to controls (respective P values 0.001, 0.001, and 0.002), while LH/FSH and testosterone levels were higher in PCOS cases than in controls (P = 0.008 and 0.003, respectively). When multivariate linear regression analyses were carried out, LH/FSH and total testosterone were positively correlated with the disease [95% confidence interval (CI) = 0.02–0.35 and 0.02–0.17, respectively], whereas FSH, SHBG, and progesterone were negatively correlated with the disease (95% CI = –0.06 to 0.001, –0.01 to 0.001, and –0.17 to –0.03, respectively), independent of age and BMI. Conclusion: Our study suggests that regardless of the age and weight factors, Saudi patients with PCOS have higher levels of LH/FSH and total testosterone; but have lower levels of FSH, SHBG, and progesterone compared to controls.