Forough Farrokhyar

A Critical Review of Epidemiological Studies in Inflammatory Bowel Disease

This review addresses the difficulty in interpreting the results of epidemiological studies in IBD and in making meaningful comparisons between studies. Both ulcerative colitis and Crohn disease appear to be more common in some industrialized countries such as Scandinavia, United Kingdom, North America and less common in Central and Southern Europe, Asia and Africa. Given data showing an increased incidence of ulcerative colitis in the United Kingdom, it is crucial that more studies be conducted in developing countries. While the incidence of Crohn disease has increased strikingly in many areas, the incidence of ulcerative colitis has remained fairly stable in most. This could be due to the rising number of community-based studies, as well as the improved accuracy in diagnosing Crohn disease. Although, the incidence of IBD among Blacks in Africa is low, infection rates are high, life expectancy is lower than in developed countries. Data from the USA suggest that rates are similar in Afro-American and Caucasian populations. Rates for Jewish populations may be slightly higher than in non-Jewish populations but this also varies geographically. Careful attention to genetic, environmental, and socioeconomic factors must be accounted for in these studies. There is no strong evidence to support that IBD is more common in urban than in rural settings and migration towards more accessible health care has not been adequately addressed. Recent epidemiological studies suggest that mortality rates for IBD are similar to that of the general population for the majority of patients. However, older patients with IBD and newly diagnosed cases with severe diseases are at increased risk of dying. Epidemiological studies remain important in assisting with health policy planning and in hypothesis testing of etiological factors. As better diagnostic techniques become widely available and public health registries are increasingly used, it is possible that geographic differences will diminish. International collaborative studies will be better equipped to answer research questions addressing risk factors and disease natural history. We have summarized in Table V the essential criteria to conduct a sound epidemiological study, which would permit future testing of hypotheses among different populations.

Functional Gastrointestinal Disorders and Mood Disorders in Patients with Inactive Inflammatory Bowel Disease: Prevalence and Impact on Health

Background: Symptoms of functional gastrointestinal disorders (FGID) associated with mood disorders (MD), such as depression and anxiety, occur in some patients with quiescent inflammatory bowel disease (IBD) and could be caused by changes in gut motility, visceral hypersensitivity, or psychological dysfunction. We assessed the prevalence of FGID symptoms and mood disorders in ambulatory patients with quiescent IBD and examined their impact on health‐related quality of life (HRQOL) and use of health resources. Methods: Consecutive ambulatory patients with IBD completed a survey of Rome II criteria for FGID, the Hospital Anxiety and Depression Survey, HRQOL indices, and health resource utilization. Logistic and linear regression analyses tested for predictors of FGID and HRQOL. Results: Of 361 patients surveyed, 149 (44 ulcerative colitis [UC] and 105 Crohns disease [CD]) had inactive IBD during the previous 12 months. Symptoms of at least 1 FGID occurred in 81.9%. Functional anorectal disorders were the most prevalent (53.7%) followed by functional bowel disorders (51.7%), and both were of greater prevalence than in the Canadian population (41.6% and 22.6%, respectively). Irritable bowel syndrome symptoms were more common in inactive CD than in UC (26% versus 9.1%, P = .01) and functional constipation was more common in inactive UC than in CD (26.2% versus 5.8%, P < .01). MD occurred in 27.3% of UC and 31.3% of CD patients. Age ≥40 years and anxiety independently predicted an FGID. Both FGID symptoms and MD were associated with impaired HRQOL and increased use of health services. Conclusions: Many patients with inactive IBD have symptoms compatible with FGID. Both FGID‐like symptoms and MD are associated with impaired HRQOL and increased health resource utilization. Recognition and treatment of FGID and MD could potentially improve daily functioning of IBD patients.

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis

IMPORTANCE Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

A Meta-analysis of Preoperative Localization Techniques for Patients with Primary Hyperparathyroidism

BackgroundReported accuracy of preoperative localization imaging for primary hyperparathyroidism (pHPT) varies. The purpose of this study is to determine the accuracy of ultrasound, sestamibi-single photon emission computed tomography (SPECT), and four-dimensional computed tomography (4D-CT) as preoperative localization strategies.MethodsA meta-analysis was performed of studies investigating the accuracy of ultrasound, sestamibi-SPECT, and 4D-CT for preoperative localization in pHPT. Electronic databases were systematically searched, and two independent reviewers reviewed results using specific criteria. Study quality was assessed using a validated measure for diagnostic imaging studies. Study heterogeneity and pooled results were calculated.Results43 studies met criteria for inclusion, and data were available for extraction in 19 ultrasound, 9 sestamibi-SPECT, and 4 4D-CT studies. Ultrasound had pooled sensitivity and positive predictive value (PPV) of 76.1% (95% CI 70.4–81.4%) and 93.2% (90.7–95.3%), respectively. Sestamibi-SPECT had pooled sensitivity and PPV of 78.9% (64–90.6%) and 90.7% (83.5–96.0%), respectively. Only two 4D-CT studies investigated patients undergoing initial parathyroidectomy. Results suggested sensitivity and PPV of 89.4% and 93.5%, respectively.ConclusionsUltrasound and sestamibi-SPECT are similar in ability to preoperatively localize abnormal parathyroid glands in pHPT. Accuracy may be improved with 4D-CT; however, further investigation is required. Choice of preoperative imaging strategy depends on numerous patient, institutional, and economic factors of which the surgeon must be aware.

Randomized Controlled Trials of Surgical Interventions

Background and Objectives:Surgical trials pose many methodological challenges often not present in trials of medical interventions. If not properly accounted for, these challenges may introduce significant biases and threaten the validity of the results. Methods:We systematically reviewed the significance of randomized controlled trials in the evaluation of surgical interventions, discussed the methodological challenges encountered in designing and conducting randomized controlled trials of surgical treatments, and proposed possible solutions to overcome these challenges. Conclusions:Many barriers and issues of surgical trials affecting internal validity can be overcome with proper methodology, and in most cases these issues do not restrict their conduct. Researchers should consider their research question carefully and design a surgical trial that contains features appropriate for the question. In doing so, they must ensure that the trial is valid, feasible, and affordable—a difficult feat, but one well worth the challenge.

The relationship between surgical factors and margin status after breast-conservation surgery for early stage breast cancer

BACKGROUND The studys aim was to identify technical factors that are predictive of negative margins after breast-conserving surgery (BCS). METHODS This was a retrospective, cohort study of patients who underwent BCS for early-stage cancer from 2000 to 2002. Pathological and specific surgical factors were compared with margin status. Univariate and multivariate regression analyses were performed. RESULTS Four hundred eighty-nine cases were reviewed. The positive margin rate after the initial surgery was 26%. In univariate analysis, lobular histology, size, grade, multifocality, and the presence of EIC and LVI were associated with positive margins (P < .05). The absence of cavity margin dissection and specimen orientation labeling, the absence of a confirmed diagnosis, and smaller volumes of excision were also associated with positive margins (P < .05). In multivariate analysis, confirmed diagnosis, small tumor size, ductal histology, absence of LVI and multifocality, palpability, cavity margin dissection, and larger volumes of excision were predictors of negative margins. CONCLUSIONS This study shows that specific surgical factors are predictive of margin status. Both tumor and technical factors should be considered when planning BCS.

Chronic Subdural Hematoma Management: A Systematic Review and Meta-analysis of 34829 Patients

Objective:To compare the efficacy and safety of multiple treatment modalities for the management of chronic subdural hematoma (CSDH) patients. Background:Current management strategies of CSDHs remain widely controversial. Treatment options vary from medical therapy and bedside procedures to major operative techniques. Methods:We searched MEDLINE (PubMed and Ovid), EMBASE, CINAHL, Google scholar, and the Cochrane library from January 1970 through February 2013 for randomized and observational studies reporting one or more outcome following the management of symptomatic patients with CSDH. Independent reviewers evaluated the quality of studies and abstracted the data on the safety and efficacy of percutaneous bedside twist-drill drainage, single or multiple operating room burr holes, craniotomy, corticosteroids as a main or adjuvant therapy, use of drains, irrigation of the hematoma cavity, bed rest, and treatment of recurrences following CSDH management. Mortality, morbidity, cure, and recurrence rates were examined for each management option. Randomized, prospective, retrospective, and overall observational studies were analyzed separately. Pooled estimates, confidence intervals (CIs), and relative risks (RRs) were calculated for all outcomes using a random-effects model. Results:A total of 34,829 patients from 250 studies met our eligibility criteria. Sixteen trials were randomized, and the remaining 234 were observational. We included our unpublished single center series of 834 patients. When comparing percutaneous bedside drainage to operating room burr hole evacuation, there was no significant difference in mortality (RR, 0.69; 95% CI, 0.46–1.05; P = 0.09), morbidity (RR, 0.45; 95% CI, 0.2–1.01; P = 0.05), cure (RR, 1.05; 95% CI, 0.98–1.11; P = 0.15), and recurrence rates (RR, 1; 95% CI, 0.66–1.52; P = 0.99). Higher morbidity was associated with the adjuvant use of corticosteroids (RR, 1.97; 95% CI, 1.54–2.45; P = 0.005), with no significant improvement in recurrence and cure rates. The use of drains following CSDH drainage resulted in a significant decrease in recurrences (RR, 0.46; 95% CI, 0.27–0.76; P = 0.002). Craniotomy was associated with higher complication rates if considered initially (RR, 1.39; 95% CI, 1.04–1.74; P = 0.01); however, craniotomy was superior to minimally invasive procedures in the management of recurrences (RR, 0.22; 95% CI, 0.05–0.85; P = 0.003). Conclusions:Percutaneous bedside twist-drill drainage is a relatively safe and effective first-line management option. These findings may result in potential health cost savings and eliminate perioperative risks related to general anesthetic.

Is There an Increased Risk of GERD After Helicobacter pylori Eradication?: A Meta-Analysis

OBJECTIVES:Some studies suggest that eradication of Helicobacter pylori (Hp) might increase the risk of gastroesophageal reflux disease (GERD) in a portion of patients. We aimed to conduct a meta-analysis to investigate this.METHODS:A comprehensive, English, multiple-source literature search was performed from 1983 to February 2007. Only randomized controlled trial (RCT) and cohort studies comparing the prevalence of GERD in patients free from GERD at baseline with Hp eradication vs. those with persistent Hp were included. Quality of RCTs and cohorts was assessed by Jadad and New Castle-Ottawa scores, respectively. Meta-analysis of pooled odds ratios (ORs) was performed using Review Manager 4.2.10.RESULTS:Twelve (7 RCTs and 5 cohorts) of 271 articles were included. In six RCTs using erosive GERD as outcome, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp group was 1.11 (0.81–1.53, P=0.52). In five RCTs using symptomatic outcome, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp was 1.22 (0.89–1.69, P=0.22). In cohort studies, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp was 1.37 (0.89–2.12; P=0.15). Test of heterogeneity was not significant for any analyses. The results were consistent in subgroup and sensitivity analyses, including cohort studies vs. RCTs, high-quality studies vs. low-quality studies, and use of endoscopic vs. symptomatic outcomes except for the subgroup of patients with peptic ulcer disease (PUD) in cohort studies (OR: 2.04 (1.08–3.85); P=0.03).CONCLUSIONS:There is no association between Hp eradication and development of new cases of GERD in the population of dyspeptic patients. However, in cohort studies, there seems to be a twofold higher risk of development of erosive GERD in patients with PUD. The effect in RCTs of patients with PUD did not show a significant difference.

Reporting of outcomes in orthopaedic randomized trials : Does blinding of outcome assessors matter?

BACKGROUND Randomization, concealment of treatment allocation, and blinding are all known to limit bias in clinical research. Nonsurgical studies that fail to meet these standards have been reported to inflate the differences between treatment and control groups. While surgical trials can rarely blind surgeons or patients, they can often blind outcome assessors. The aim of this systematic review was threefold: (1) to examine the reporting of outcome measures in orthopaedic trials, (2) to determine the feasibility of blinding in published orthopaedic trials, and (3) to examine the association between the magnitude of treatment differences and the blinding of outcome assessors. METHODS We identified and reviewed thirty-two randomized, controlled trials published in The Journal of Bone and Joint Surgery (American Volume) in 2003 and 2004 for the appropriate use of outcome measures. These trials represented 3.4% of all 938 studies published during that time-period. All thirty-two trials were reviewed by two authors for (1) the outcome measures used and (2) the blinding of outcomes assessors. We calculated the magnitude of the treatment effect of the use of blinded compared with unblinded outcome assessors. RESULTS Ten (31%) of the thirty-two randomized controlled trials used a modified outcome instrument. Of the ten trials, four failed to describe how the outcome instrument was modified. Nine of the ten articles did not describe how the modified instrument was validated and retested. Sixteen of the thirty-two randomized controlled trials did not report blinding of outcome assessors when blinding would have been possible. Among the studies with continuous outcome measure, unblinded outcomes assessment was associated with significantly larger treatment effects than blinded outcomes assessment (standardized mean difference, 0.76 compared with 0.25; p = 0.01). Similarly, in the studies with dichotomous outcomes, unblinded outcomes assessments were associated with significantly greater treatment effects than blinded outcomes assessments (odds ratio, 0.13 compared with 0.42; p < 0.001). The ratio of odds ratios (unblinded to blinded outcomes assessment) was 0.31, suggesting that unblinded outcomes assessment was associated with a potential for exaggeration of the benefit of the effectiveness of a treatment in our cohort of studies. CONCLUSIONS In future orthopaedic randomized controlled trials, emphasis should be placed on detailed reporting of outcome measures to facilitate generalization and the outcome assessors should be blinded, when possible, to limit bias.

Systematic review of flexor tendon rehabilitation protocols in zone II of the hand.

Background: Restoration of function following flexor tendon repair in zone II represents a difficult clinical problem. Despite many publications on rehabilitation methods, there exists no consensus as to which method is superior. This study was undertaken to determine which flexor tendon rehabilitation protocol provides the best outcome after surgical repair in zone II. Methods: Electronic databases were searched for articles published between 1970 and 2009. The population included patients aged 5 years and older who sustained a flexor tendon laceration in zone II. The primary outcome was rupture rate. Secondary outcomes were range of motion and quality of life. The following protocols and their variations were considered: passive flexion and active extension protocols (Kleinert type protocols), controlled passive motion protocols (Duran type protocols), combination of the Kleinert and Duran protocols, and early active motion protocols. Results: Seventy-nine articles were identified. Fifteen studies met the inclusion criteria. The mean rate of rupture was lowest in the combined Kleinert and Duran protocols (2.3 percent) and highest in the Kleinert protocols (7.1 percent). No statistically significant differences were found. The combined Kleinert and Duran protocols and the early active motion protocols exhibited the highest proportion of digits with excellent or good results using the Strickland and Buck-Gramcko systems. One study included a quality-of-life assessment—meaningful comparison was not possible. Conclusions: Both early active motion protocols and combined Kleinert and Duran protocols result in low rates of tendon rupture and acceptable range of motion following flexor tendon repair in zone II. Future studies should include quality-of-life measurements using validated scales.