Belal Firwana

Patient engagement in research: a systematic review

BackgroundA compelling ethical rationale supports patient engagement in healthcare research. It is also assumed that patient engagement will lead to research findings that are more pertinent to patients’ concerns and dilemmas. However; it is unclear how to best conduct this process. In this systematic review we aimed to answer 4 key questions: what are the best ways to identify patient representatives? How to engage them in designing and conducting research? What are the observed benefits of patient engagement? What are the harms and barriers of patient engagement?MethodsWe searched MEDLINE, EMBASE, PsycInfo, Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier, Academic Search Premier and Google Scholar. Included studies were published in English, of any size or design that described engaging patients or their surrogates in research design. We conducted an environmental scan of the grey literature and consulted with experts and patients. Data were analyzed using a non-quantitative, meta-narrative approach.ResultsWe included 142 studies that described a spectrum of engagement. In general, engagement was feasible in most settings and most commonly done in the beginning of research (agenda setting and protocol development) and less commonly during the execution and translation of research. We found no comparative analytic studies to recommend a particular method. Patient engagement increased study enrollment rates and aided researchers in securing funding, designing study protocols and choosing relevant outcomes. The most commonly cited challenges were related to logistics (extra time and funding needed for engagement) and to an overarching worry of a tokenistic engagement.ConclusionsPatient engagement in healthcare research is likely feasible in many settings. However, this engagement comes at a cost and can become tokenistic. Research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.

Patient and service user engagement in research: a systematic review and synthesized framework

There is growing attention towards increasing patient and service user engagement (PSUE) in biomedical and health services research. Existing variations in language and design inhibit reporting and indexing, which are crucial to comparative effectiveness in determining best practices.

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.

Comprehensive review of JAK inhibitors in myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as ‘BCR-ABL1-negative’ MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in ‘BCR-ABL1-negative’ MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate- to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.

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.

Tumor Lysis Syndrome: A Systematic Review of Case Series and Case Reports

Abstract Tumor lysis syndrome (TLS) is a clinical condition that is caused by a massive lysis of tumor cells that accumulate very rapidly and disturb hemodynamics. This oncologic emergency requires immediate intervention. Tumor lysis syndrome was first described in the 19th century. Since then, it has become a well–known disease with improved management measures. Tumor lysis syndrome can occur after any type of neoplasm. It is highly associated with rapidly proliferating tumors compared with those that are well demarcated, such as acute lymphoblastic leukemia and high–grade non–Hodgkin lymphoma. Initiation of chemotherapy, radiotherapy, or steroid treatment may trigger TLS, or it may develop spontaneously. The release of massive quantities of intracellular contents may produce hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure. Prevention and treatment measures include intravenous hydration, use of allopurinol and rasburicase, management of TLS–associated electrolyte abnormalities, and renal replacement therapy; the use of urine alkalinization remains controversial. In this article, we summarize the findings of case series and case reports published over the past 6 years in an effort to help familiarize clinicians better recognize and manage TLS.

A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome

OBJECTIVE The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less intensive glycemic control in preventing diabetic foot syndrome. METHODS We used the umbrella design (systematic review of systematic reviews) to identify eligible RCTs. Two reviewers determined RCT eligibility and extracted descriptive, methodologic, and diabetic foot outcome data. Random-effects meta-analysis was used to pool outcome data across studies, and the I(2) statistic was used to quantify heterogeneity. RESULTS Nine RCTs enrolling 10,897 patients with type 2 diabetes were included and deemed to be at moderate risk of bias. Compared with less intensive glycemic control, intensive control (hemoglobin A1c, 6%-7.5%) was associated with a significant decrease in risk of amputation (relative risk [RR], 0.65; 95% confidence interval [CI], 0.45-0.94; I(2) = 0%). Intensive control was significantly associated with slower decline in sensory vibration threshold (mean difference, -8.27; 95% CI, -9.75 to -6.79). There was no effect on other neuropathic changes (RR, 0.89; 95% CI, 0.75-1.05; I(2) = 32%) or ischemic changes (RR, 0.92; 95% CI, 0.67-1.26; I(2) = 0%). The quality of evidence is likely moderate. CONCLUSIONS Compared with less intensive glycemic control therapy, intensive control may decrease the risk of amputation in patients with diabetic foot syndrome. The reported risk reduction is likely overestimated because the trials were open and the decision to proceed with amputation could be influenced by glycemic control.

Health assessment of commercial drivers: a meta-narrative systematic review

Background Motor vehicle accidents associated with commercial driving are an important cause of occupational death and impact public safety. Objectives We summarise the evidence regarding the type, prevalence and impact of medical conditions discovered during health assessment of commercial drivers. Evidence review We conducted a systematic review of multiple electronic databases and made a manual search for relevant studies that enrolled commercial drivers in any country and reported the outcomes of health assessment carried out in the context of commercial driving through November 2012. Data were extracted by a pair of independent reviewers and synthesised using a metanarrative approach. Results We identified 32 studies of moderate methodological quality enrolling 151 644 commercial drivers (98% men). The prevalence of multiple health conditions was high (sleep disorders 19%, diabetes 33%, hypertension 23% and obesity 45%). Some conditions, such as sleep disorders and obesity, were linked to increased risk of crashes. Evidence on several other highly relevant medical conditions was lacking. Cost-effectiveness data were sparse. Conclusions Several medical conditions are highly prevalent in commercial drivers and can be associated with increased risk of crashes, thus providing a rationale for health assessment of commercial drivers.

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers

BACKGROUND Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting. METHODS We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest were complete wound healing and amputation. RESULTS We identified 18 interventional studies; of which 9 were randomized, enrolling 1526 patients. The risk of bias in the included studies was moderate. In multiple randomized trials, the addition of HBOT to conventional therapy (wound care and offloading) was associated with increased healing rate (Peto odds ratio, 14.25; 95% confidence interval, 7.08-28.68) and reduced major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10-0.89), compared with conventional therapy alone. In one small trial, arterial pump devices had a favorable effect on complete healing compared with HBOT and in another small trial compared with placebo devices. Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy. No comparative studies were identified for cilostazol in diabetic foot ulcers. CONCLUSIONS There is low- to moderate-quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation. However, there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions.

A systematic review and meta-analysis of tests to predict wound healing in diabetic foot

BACKGROUND This systematic review summarized the evidence on noninvasive screening tests for the prediction of wound healing and the risk of amputation in diabetic foot ulcers. METHODS We searched MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Scopus from database inception to October 2011. We pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and compared test performance. RESULTS Thirty-seven studies met the inclusion criteria. Eight tests were used to predict wound healing in this setting, including ankle-brachial index (ABI), ankle peak systolic velocity, transcutaneous oxygen measurement (TcPo2), toe-brachial index, toe systolic blood pressure, microvascular oxygen saturation, skin perfusion pressure, and hyperspectral imaging. For the TcPo2 test, the pooled DOR was 15.81 (95% confidence interval [CI], 3.36-74.45) for wound healing and 4.14 (95% CI, 2.98-5.76) for the risk of amputation. ABI was also predictive but to a lesser degree of the risk of amputations (DOR, 2.89; 95% CI, 1.65-5.05) but not of wound healing (DOR, 1.02; 95% CI, 0.40-2.64). It was not feasible to perform meta-analysis comparing the remaining tests. The overall quality of evidence was limited by the risk of bias and imprecision (wide CIs due to small sample size). CONCLUSIONS Several tests may predict wound healing in the setting of diabetic foot ulcer; however, most of the available evidence evaluates only TcPo2 and ABI. The overall quality of the evidence is low, and further research is needed to provide higher quality comparative effectiveness evidence.