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1.  Midodrine for Orthostatic Hypotension: A Systematic Review and Meta-Analysis of Clinical Trials 
Journal of General Internal Medicine  2013;28(11):1496-1503.
To perform a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of midodrine in orthostatic hypotension (OH).
We searched major databases and related conference proceedings through June 30, 2012. Two reviewers independently selected studies and extracted data. Random-effects meta-analysis was used to pool the outcome measures across studies.
Seven trials were included in the efficacy analysis (enrolling 325 patients, mean age 53 years) and two additional trials were included in the safety analysis. Compared to placebo, the mean change in systolic blood pressure was 4.9 mmHg (p = 0.65) and the mean change in mean arterial pressure from supine to standing was −1.7 mmHg (p = 0.45). The change in standing systolic blood pressure before and after giving midodrine was 21.5 mmHg (p < 0.001). A significant improvement was seen in patients’ and investigators’ global assessment symptoms scale (a mean difference of 0.70 [95 % CI 0.30–1.09; p < 0.001] and 0.80 [95 % CI 0.76–0.85; p < 0.001], respectively). There was a significant increase in risk of piloerection, scalp pruritis, urinary hesitancy/retention, supine hypertension and scalp paresthesia after giving midodrine. The quality of evidence was limited by imprecision, heterogeneity and increased risk of bias.
There is insufficient and low quality evidence to support the use of midodrine for OH.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-013-2520-3) contains supplementary material, which is available to authorized users.
PMCID: PMC3797331  PMID: 23775146
orthostatic hypotension; midodrine; systematic review; meta-analysis; efficacy; safety
2.  The Efficacy of Resiliency Training Programs: A Systematic Review and Meta-Analysis of Randomized Trials 
PLoS ONE  2014;9(10):e111420.
Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders.
To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases.
Data Sources
Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts.
Study Selection
Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used.
Data Extraction and Synthesis
Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups.
Main Outcomes
The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety.
We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I2 = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I2 = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I2 = 61%].
We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it.
Registration Number
PROSPERO #CRD42014007185
PMCID: PMC4210242  PMID: 25347713
3.  A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 
Lim, Stephen S | Vos, Theo | Flaxman, Abraham D | Danaei, Goodarz | Shibuya, Kenji | Adair-Rohani, Heather | Amann, Markus | Anderson, H Ross | Andrews, Kathryn G | Aryee, Martin | Atkinson, Charles | Bacchus, Loraine J | Bahalim, Adil N | Balakrishnan, Kalpana | Balmes, John | Barker-Collo, Suzanne | Baxter, Amanda | Bell, Michelle L | Blore, Jed D | Blyth, Fiona | Bonner, Carissa | Borges, Guilherme | Bourne, Rupert | Boussinesq, Michel | Brauer, Michael | Brooks, Peter | Bruce, Nigel G | Brunekreef, Bert | Bryan-Hancock, Claire | Bucello, Chiara | Buchbinder, Rachelle | Bull, Fiona | Burnett, Richard T | Byers, Tim E | Calabria, Bianca | Carapetis, Jonathan | Carnahan, Emily | Chafe, Zoe | Charlson, Fiona | Chen, Honglei | Chen, Jian Shen | Cheng, Andrew Tai-Ann | Child, Jennifer Christine | Cohen, Aaron | Colson, K Ellicott | Cowie, Benjamin C | Darby, Sarah | Darling, Susan | Davis, Adrian | Degenhardt, Louisa | Dentener, Frank | Des Jarlais, Don C | Devries, Karen | Dherani, Mukesh | Ding, Eric L | Dorsey, E Ray | Driscoll, Tim | Edmond, Karen | Ali, Suad Eltahir | Engell, Rebecca E | Erwin, Patricia J | Fahimi, Saman | Falder, Gail | Farzadfar, Farshad | Ferrari, Alize | Finucane, Mariel M | Flaxman, Seth | Fowkes, Francis Gerry R | Freedman, Greg | Freeman, Michael K | Gakidou, Emmanuela | Ghosh, Santu | Giovannucci, Edward | Gmel, Gerhard | Graham, Kathryn | Grainger, Rebecca | Grant, Bridget | Gunnell, David | Gutierrez, Hialy R | Hall, Wayne | Hoek, Hans W | Hogan, Anthony | Hosgood, H Dean | Hoy, Damian | Hu, Howard | Hubbell, Bryan J | Hutchings, Sally J | Ibeanusi, Sydney E | Jacklyn, Gemma L | Jasrasaria, Rashmi | Jonas, Jost B | Kan, Haidong | Kanis, John A | Kassebaum, Nicholas | Kawakami, Norito | Khang, Young-Ho | Khatibzadeh, Shahab | Khoo, Jon-Paul | Kok, Cindy | Laden, Francine | Lalloo, Ratilal | Lan, Qing | Lathlean, Tim | Leasher, Janet L | Leigh, James | Li, Yang | Lin, John Kent | Lipshultz, Steven E | London, Stephanie | Lozano, Rafael | Lu, Yuan | Mak, Joelle | Malekzadeh, Reza | Mallinger, Leslie | Marcenes, Wagner | March, Lyn | Marks, Robin | Martin, Randall | McGale, Paul | McGrath, John | Mehta, Sumi | Mensah, George A | Merriman, Tony R | Micha, Renata | Michaud, Catherine | Mishra, Vinod | Hanafiah, Khayriyyah Mohd | Mokdad, Ali A | Morawska, Lidia | Mozaff arian, Dariush | Murphy, Tasha | Naghavi, Mohsen | Neal, Bruce | Nelson, Paul K | Nolla, Joan Miquel | Norman, Rosana | Olives, Casey | Omer, Saad B | Orchard, Jessica | Osborne, Richard | Ostro, Bart | Page, Andrew | Pandey, Kiran D | Parry, Charles D H | Passmore, Erin | Patra, Jayadeep | Pearce, Neil | Pelizzari, Pamela M | Petzold, Max | Phillips, Michael R | Pope, Dan | Pope III, C Arden | Powles, John | Rao, Mayuree | Razavi, Homie | Rehfuess, Eva A | Rehm, Jürgen T | Ritz, Beate | Rivara, Frederick P | Roberts, Thomas | Robinson, Carolyn | Rodriguez-Portales, Jose A | Romieu, Isabelle | Room, Robin | Rosenfeld, Lisa C | Roy, Ananya | Rushton, Lesley | Salomon, Joshua A | Sampson, Uchechukwu | Sanchez-Riera, Lidia | Sanman, Ella | Sapkota, Amir | Seedat, Soraya | Shi, Peilin | Shield, Kevin | Shivakoti, Rupak | Singh, Gitanjali M | Sleet, David A | Smith, Emma | Smith, Kirk R | Stapelberg, Nicolas J C | Steenland, Kyle | Stöckl, Heidi | Stovner, Lars Jacob | Straif, Kurt | Straney, Lahn | Thurston, George D | Tran, Jimmy H | Van Dingenen, Rita | van Donkelaar, Aaron | Veerman, J Lennert | Vijayakumar, Lakshmi | Weintraub, Robert | Weissman, Myrna M | White, Richard A | Whiteford, Harvey | Wiersma, Steven T | Wilkinson, James D | Williams, Hywel C | Williams, Warwick | Wilson, Nicholas | Woolf, Anthony D | Yip, Paul | Zielinski, Jan M | Lopez, Alan D | Murray, Christopher J L | Ezzati, Majid
Lancet  2012;380(9859):2224-2260.
Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time.
We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden.
In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania.
Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.
Bill & Melinda Gates Foundation.
PMCID: PMC4156511  PMID: 23245609
4.  Submucosal fibroids and the relation to heavy menstrual bleeding and anemia 
To determine the contribution of submucosal fibroids to heavy menstrual bleeding (HMB) and anemia among women with HMB.
Study Design
Our retrospective study included premenopausal women, who presented to a tertiary care center for HMB between January, 2007 and October, 2011. All women in this cohort underwent flexible office hysteroscopy (n=1,665) and 259 (15.6%) had submucosal fibroids. We also reviewed clinical ultrasounds (n=914) from these women to determine if submucosal fibroids (n=148) or any fibroids (n=434) were present in the uterus. Clinical evaluation of bleeding included hemoglobin and pictorial blood loss assessment charts (PBLAC).
In our cohort, hysteroscopically-diagnosed submucosal fibroids were associated with significantly lower hemoglobin (adjusted difference −0.35 g/dL (95% confidence interval (CI) −0.56 g/dL, −0.13g/dL) and higher risk of anemia (odds ratio (OR) 1.46, 95% CI 1.04, 2.03). Women with ultrasound-diagnosed submucosal fibroids had lower hemoglobin and anemia, but results were not significant once adjusted for confounders (hemoglobin: adjusted difference −0.21 g/dL, 95%CI −0.47g/dL, 0.06g/dL and anemia: OR 1.28, 95% CI 0.82, 1.97). Ultrasound-diagnosed fibroids anywhere in the uterus were not associated with hemoglobin (p=0.7) or anemia (p=0.8). Self-reported PBLAC scores did not differ between women with and without fibroids diagnosed by either hysteroscopy or ultrasound (p=0.4 & 0.9 respectively).
Submucosal fibroids were related to lower hemoglobin and higher risk of anemia, but not self-reported bleeding scores. Diagnostic modality was important: hysteroscopically-diagnosed submucosal fibroids had lower hemoglobin and more anemia than ultrasound-diagnosed submucosal fibroids. This may explain inconsistent results in the literature.
PMCID: PMC4142474  PMID: 24080304
anemia; office hysteroscopy; pictorial blood loss assessment score; submucosal fibroid; ultrasound
5.  Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: Systematic Review and Meta-Analysis 
Hepatology (Baltimore, Md.)  2010;52(4):1360-1370.
Sirolimus is used in patients with renal insufficiency following liver transplantation (LT), especially in those with calcineurin inhibitor (CNI) associated nephrotoxicity.
We conducted a systematic review of all randomized controlled trials (RCTs) and observational studies to test the hypothesis that use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency (GFR<60ml/min or creatinine≥1.5mg/dL).
We performed a search of all major databases, conference proceedings and relevant journals through December 2009 and contacted content experts, corresponding authors, and the pharmaceutical manufacturer. A random effects model was utilized to determine the pooled estimate of the change in renal function and pooled risk estimates of adverse events that may be associated with sirolimus based therapy at 1 year.
Eleven studies (3 RCTs and 8 observational) met final inclusion criteria. A non significant improvement of 3.38 ml/min (95% CI -2.93 to 9.69) was observed among methodologically sound observational studies and controlled trials reporting the primary outcome. Among controlled trials, sirolimus use was associated with a 10.35 ml/min (95% CI 3.98 - 16.77) improvement in GFR or creatinine clearance. Sirolimus was not significantly associated with death, RR=1.12 (95% CI 0.66-1.88) or graft failure, RR=0.80 (95% CI 0.45-1.41), though reporting was incomplete. It was associated with a statistically significant risk of infection (RR=2.47, 95% CI 1.14-5.36), rash (RR=7.57, 95% CI 1.75-32.70), ulcers (RR=7.44, 95% CI 2.03-27.28) and discontinuation of therapy (RR=3.61, 95% CI 1.32-9.89).
Conversion to sirolimus from CNI is associated with a non significant improvement in renal function in LT recipients with renal insufficiency, though results are limited by heterogeneity, risk of bias, and lack of standardized reporting.
PMCID: PMC4130484  PMID: 20815021
side effects; rapamycin; mTOR Inhibitor; calcineurin inhibitors
6.  Association of Mediterranean diet with Mild Cognitive Impairment and Alzheimer’s disease: A Systematic Review and Meta-Analysis 
To conduct a systematic review of all studies to determine whether there is an association between the Mediterranean diet (MeDi) and cognitive impairment.
We conducted a comprehensive search of the major databases and hand-searched proceedings of major neurology, psychiatry, and dementia conferences through November 2012. Prospective cohort studies examining the MeDi with longitudinal follow-up of at least 1 year and reporting cognitive outcomes (mild cognitive impairment [MCI] or Alzheimer’s disease [AD]) were included. The effect size was estimated as hazard-ratio (HR) with 95% confidence intervals (CIs) using the random-effects model. Heterogeneity was assessed using Cochran’s Q-test and I2-statistic.
Out of the 664 studies screened, five studies met eligibility criteria. Higher adherence to the MeDi was associated with reduced risk of MCI and AD. The subjects in the highest MeDi tertile had 33% less risk (adjusted HR=0.67; 95% CI, 0.55–0.81; P<0.0001) of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI (HR=0.73; 95% CI, 0.56–0.96; P=0.02) and AD (HR=0.64; 95% CI, 0.46–0.89; P=0.007). There was no significant heterogeneity in the analyses.
While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD. Further prospective-cohort studies with longer follow-up and randomized controlled trials are warranted to consolidate the evidence.
PMCID: PMC3946820  PMID: 24164735
Mediterranean diet; MCI; Mild Cognitive Impairment; Alzheimer’s disease; systematic review; meta-analysis
7.  The association of 9p21-3 locus with coronary atherosclerosis: a systematic review and meta-analysis 
BMC Medical Genetics  2014;15:66.
Studies suggest that the 9p21-3 locus may influence susceptibility to myocardial infarction. We performed a systematic review and meta-analysis to assess whether this locus is associated with severity of coronary atherosclerosis and adverse clinical outcomes in those with known coronary disease.
Multiple electronic databases were searched from inception through August 2012. Studies examining 9p21-3 genotype in patients with known coronary artery disease were included. We extracted the association of the 9p21-3 locus with measures of severity of coronary atherosclerosis [number of diseased vessels, Gensini Score, Duke CAD Prognostic Index (DPI)], angiographic outcomes [change in minimum lumen diameter (∆MLD) and number of new lesions at follow-up], and key clinical outcomes (all-cause mortality, recurrent myocardial infarction and the need for coronary revascularization). Relative risks (RR) and weighted mean difference (WMD) were pooled using the random effects models.
23 cohorts enrolling 16,860 participants were analyzed. There was no significant difference between HR and LR genotypes in terms of all-cause mortality, recurrent myocardial infarction or the frequency of coronary revascularization. HR genotype was associated with increased risk of triple vessel disease (RR = 1.34; 95% CI 1.08-1.65; P = 0.01) and increased baseline Gensini Score (WMD = 5.30; 95% CI 0.66-9.93; P = 0.03). However there was no association with DPI (WMD = 4.00; 95% CI 2.94-10.94; P = 0.26). HR genotype did not predict ∆MLD or number of new lesions at follow-up.
Patients of coronary atherosclerosis who carry the high risk genotype of the 9p21-3 allele may be more likely to have multi-vessel CAD. However the effect of this allele on CAD progression and disease specific clinical outcomes are not observed possibly due to diminishing genetic risk following dietary modification and therapy.
PMCID: PMC4074865  PMID: 24906238
Coronary; Atherosclerosis; 9p21-3
8.  Beyond pain in fibromyalgia: insights into the symptom of fatigue 
Fatigue is a disabling, multifaceted symptom that is highly prevalent and stubbornly persistent. Although fatigue is a frequent complaint among patients with fibromyalgia, it has not received the same attention as pain. Reasons for this include lack of standardized nomenclature to communicate about fatigue, lack of evidence-based guidelines for fatigue assessment, and a deficiency in effective treatment strategies. Fatigue does not occur in isolation; rather, it is present concurrently in varying severity with other fibromyalgia symptoms such as chronic widespread pain, unrefreshing sleep, anxiety, depression, cognitive difficulties, and so on. Survey-based and preliminary mechanistic studies indicate that multiple symptoms feed into fatigue and it may be associated with a variety of physiological mechanisms. Therefore, fatigue assessment in clinical and research settings must consider this multi-dimensionality. While no clinical trial to date has specifically targeted fatigue, randomized controlled trials, systematic reviews, and meta-analyses indicate that treatment modalities studied in the context of other fibromyalgia symptoms could also improve fatigue. The Outcome Measures in Rheumatology (OMERACT) Fibromyalgia Working Group and the Patient Reported Outcomes Measurement Information System (PROMIS) have been instrumental in propelling the study of fatigue in fibromyalgia to the forefront. The ongoing efforts by PROMIS to develop a brief fibromyalgia-specific fatigue measure for use in clinical and research settings will help define fatigue, allow for better assessment, and advance our understanding of fatigue.
PMCID: PMC3978642  PMID: 24289848
9.  Efficacy of Continuous Glucose Monitoring in Improving Glycemic Control and Reducing Hypoglycemia: A Systematic Review and Meta-Analysis of Randomized Trials 
We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG).
We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model.
Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30) and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-realtime devices (WMD -0.22%, 95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews.
Continuous glucose monitoring seems to help improve glycemic control in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise and unclear. Larger trials with longer follow-up are needed to assess the efficacy of CGM in reducing patient-important complications without significantly increasing the burden of care for patients with diabetes.
PMCID: PMC3192603  PMID: 21880239
biosensing techniques; blood glucose self-monitoring; diabetes mellitus
10.  A systematic review of shared decision making interventions in chronic conditions: a review protocol 
Systematic Reviews  2014;3:38.
Chronic conditions are a major source of morbidity, mortality and cost worldwide. Shared decision making is one way to improve care for patients with chronic conditions. Although it has been widely studied, the effect of shared decision making in the context of chronic conditions is unknown.
We will perform a systematic review with the objective of determining the effectiveness of shared decision making interventions for persons diagnosed with chronic conditions. We will search the following databases for relevant articles: PubMed, Scopus, Ovid MEDLINE, Ovid EMBASE, Ovid EBM Reviews CENTRAL, CINAHL, and Ovid PsycInfo. We will also search clinical trial registries and contact experts in the field to identify additional studies. We will include randomized controlled trials studying shared decision making interventions in patients with chronic conditions who are facing an actual decision. Shared decision making interventions will be defined as any intervention aiming to facilitate or improve patient and/or clinician engagement in a decision making process. We will describe all studies and assess their quality. After adjusting for missing data, we will analyze the effect of shared decision making interventions on outcomes in chronic conditions overall and stratified by condition. We will evaluate outcomes according to an importance ranking informed by a variety of stakeholders. We will perform several exploratory analyses including the effect of author contact on the estimates of effect.
We anticipate that this systematic review may have some limitations such as heterogeneity and imprecision; however, the results will contribute to improving the quality of care for individuals with chronic conditions and facilitate a process that allows decision making that is most consistent with their own values and preferences.
Trial registration
PROSPERO Registration Number: CRD42013005784
PMCID: PMC4021633  PMID: 24731616
Protocol; Systematic review; Chronic condition; Chronic disease; Chronic illness; Shared decision making; Decision making; Decision support tool; Decision aid
11.  The efficacy of resilience training programs: a systematic review protocol 
Systematic Reviews  2014;3:20.
Resilience has been defined as the ability of individuals to manage and adapt to stress and life challenges. Training programs that develop and/or enhance resilience may have efficacy in improving health, well-being, and quality of life. Because patients with chronic conditions must reliably self-manage their health, strategies to bolster resilience in this population may be of particular value. The objectives of this systematic review are to synthesize the evidence of resilience training program efficacy in improving outcomes related to quality of life, self-efficacy and activation, and resilience and coping ability in: 1) diverse adult populations; and 2) patients with chronic conditions.
We will conduct a systematic review of randomized controlled trials assessing the efficacy of any program designed to enhance resilience in adults that measure any outcome against any comparator. We will search multiple electronic databases, trial registries, bibliographies, and will contact authors and experts to identify studies. We will use systematic review software to independently and in duplicate screen reports and extract data. We will extract characteristics of the study populations, interventions, comparators, outcomes, and quality/risk of bias. Primary, patient reported outcomes will be categorized into domains of quality of life, self-efficacy, and resilience. Secondary outcomes will be considered based on findings of the review. We will attempt meta-analysis by pooling standardized mean differences and minimally important differences (MIDs), when possible. Planned trial subgroup analyses are: 1) studies of patients with chronic conditions; 2) studies with placebo controls; 3) studies with similar intervention characteristics; and 4) studies with common lengths of follow-up.
This study is intended to accumulate the evidence for resilience training programs in improving quality of life, resilience, and self-efficacy for care management, particularly among adult patients with chronic conditions. Its findings will be valuable to policy-makers, funding agencies, clinicians, and patients seeking innovative and effective ways to achieve patient-centered care.
Trial registration
PROSPERO registration number: CRD42014007185.
PMCID: PMC3946765  PMID: 24602236
Resilience; Resilience training; Systematic review; Randomized controlled trials
12.  Delayed surgical debridement in pediatric open fractures: a systematic review and meta-analysis 
Open fractures are considered orthopedic emergencies that are traditionally treated with surgical debridement within 6 h of injury to prevent infection. However, this proclaimed “6-h rule” is arbitrary and not based on rigorous scientific evidence. The aim of our study was to systematically review the literature that compares late (>6 h from the time of injury) to early (<6 h from the time of injury) surgical debridement of pediatric open fractures.
We searched several databases from 1946 to 2013 for any observational or experimental studies that evaluated late and early surgical debridement of pediatric open fractures. We performed a meta-analysis using a random effects model to pool odds ratios for a comparison of infection rates between children undergoing late versus early surgical debridement. We also investigated the infection rates in upper- and lower-limb pediatric open fractures. Descriptive, quantitative, and qualitative data were extracted.
Of the 12 articles identified, three studies (retrospective cohort studies) were eligible for the meta-analysis, encompassing a total of 714 open fractures. The pooled odds ratio (OR = 0.79) for infection between late and early surgical debridement was in favor of late surgical debridement but was not statistically significant (95 % CI 0.32, 1.99; p = 0.38, I2 = 0 %). No significant difference in infection rate was detected between pediatric open fractures in the upper and lower limbs according to the time threshold in the included studies (OR = 0.72, 95 % CI 0.29, 1.82; p = 0.40, I2 = 0 %).
The cumulative evidence does not, at present, indicate an association between late surgical debridement and higher infection rates in pediatric open fractures. However, initial expedient surgical debridement of open fractures in children should always remain the rule. Thus, multi-center randomized controlled trials or prospective cohort studies will be able to answer this question with more certainty and a higher level of evidence.
Level of evidence
Level III.
PMCID: PMC3965772  PMID: 24554129
Open fracture; Children; Debridement; Meta-analysis; Systematic review
13.  Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design 
Trials  2013;14:335.
Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.
We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs’). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.
To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.
PMCID: PMC3874848  PMID: 24131702
Randomized controlled trials stopped early for benefit; RCT; Systematic review; Protocol
14.  Improving understanding in the research informed consent process: a systematic review of 54 interventions tested in randomized control trials 
BMC Medical Ethics  2013;14:28.
Obtaining informed consent is a cornerstone of biomedical research, yet participants comprehension of presented information is often low. The most effective interventions to improve understanding rates have not been identified.
To systematically analyze the random controlled trials testing interventions to research informed consent process. The primary outcome of interest was quantitative rates of participant understanding; secondary outcomes were rates of information retention, satisfaction, and accrual. Interventional categories included multimedia, enhanced consent documents, extended discussions, test/feedback quizzes, and miscellaneous methods.
The search spanned from database inception through September 2010. It was run on Ovid MEDLINE, Ovid EMBASE, Ovid CINAHL, Ovid PsycInfo and Cochrane CENTRAL, ISI Web of Science and Scopus. Five reviewers working independently and in duplicate screened full abstract text to determine eligibility. We included only RCTs. 39 out of 1523 articles fulfilled review criteria (2.6%), with a total of 54 interventions. A data extraction form was created in Distiller, an online reference management system, through an iterative process. One author collected data on study design, population, demographics, intervention, and analytical technique.
Meta-analysis was possible on 22 interventions: multimedia, enhanced form, and extended discussion categories; all 54 interventions were assessed by review. Meta-analysis of multimedia approaches was associated with a non-significant increase in understanding scores (SMD 0.30, 95% CI, -0.23 to 0.84); enhanced consent form, with significant increase (SMD 1.73, 95% CI, 0.99 to 2.47); and extended discussion, with significant increase (SMD 0.53, 95% CI, 0.21 to 0.84). By review, 31% of multimedia interventions showed significant improvement in understanding; 41% for enhanced consent form; 50% for extended discussion; 33% for test/feedback; and 29% for miscellaneous.Multiple sources of variation existed between included studies: control processes, the presence of a human proctor, real vs. simulated protocol, and assessment formats.
Enhanced consent forms and extended discussions were most effective in improving participant understanding. Interventions of all categories had no negative impact on participant satisfaction or study accrual. Identification of best practices for studies of informed consent interventions would aid future systematic comparisons.
PMCID: PMC3733934  PMID: 23879694
Informed consent; Comprehension; Systematic review
15.  Uncovering Treatment Burden as a Key Concept for Stroke Care: A Systematic Review of Qualitative Research 
PLoS Medicine  2013;10(6):e1001473.
In a systematic review of qualitative research, Katie Gallacher and colleagues examine the evidence related to treatment burden after stroke from the patient perspective.
Please see later in the article for the Editors' Summary
Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.
Methods and Findings
The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.
Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems.
Systematic Review Registration
International Prospective Register of Systematic Reviews CRD42011001123
Please see later in the article for the Editors' Summary
Editors' Summary
Every year, 15 million people have a stroke. About 5 million of these people die within a few days, and another 5 million are left disabled. Stroke occurs when the blood supply of the brain is suddenly interrupted by a blood vessel in the brain being blocked by a blood clot (ischemic stroke) or bursting (hemorrhagic stroke). Deprived of the oxygen normally carried to them by the blood, the brain cells near the blockage die. The symptoms of stroke depend on which part of the brain is damaged but include sudden weakness or paralysis along one side of the body, vision loss in one or both eyes, and confusion or trouble speaking or understanding speech. Anyone experiencing these symptoms should seek immediate medical attention because prompt treatment can limit the damage to the brain. In the longer term, post-stroke rehabilitation can help individuals overcome the physical disabilities caused by stroke, and drugs that thin the blood, reduce blood pressure and reduce cholesterol (major risk factors for stroke) alongside behavioral counseling can reduce the risk of a second stroke.
Why Was This Study Done?
Treatment for, and rehabilitation from, stroke is a lengthy process that requires considerable personal investment from the patient. The term “treatment burden” describes the self-care practices that patients with stroke and other chronic diseases must perform to follow the complicated management strategies that have been developed for these conditions. Unfortunately, treatment burden can overwhelm patients. They may be unable to cope with the multiple demands placed on them by health-care providers and systems for their self-care, a situation that leads to poor adherence to therapies and poor outcomes. For example, patients may find it hard to complete all the exercises designed to help them regain full movement of their limbs after a stroke. Treatment burden has been poorly examined in relation to stroke. Here, the researchers identify and describe the treatment burden in stroke by undertaking a systematic review (a study that uses predefined criteria to identify all the literature on a given topic) of qualitative studies on the patient experience of stroke management. Qualitative studies collect non-quantitative data so, for example, a qualitative study on stroke treatment might ask people how the treatment made them feel whereas a quantitative study might compare clinical outcomes between those receiving and not receiving the treatment.
What Did the Researchers Do and Find?
The researchers identified 69 qualitative studies dealing with the experiences of stroke management of adult patients and analyzed the data in these papers using framework synthesis—an approach that divides data into thematic categories. Specifically, the researchers used a coding framework informed by normalization process theory, a sociological theory of the implementation, embedding and integration of tasks and practices; embedding is the process of making tasks and practices a routine part of everyday life and integration refers to sustaining these embedded practices. The researchers identified four main areas of treatment burden for stroke: making sense of stroke management and planning care; interacting with others, including health care professionals, family and other patients with stroke; enacting management strategies (including enduring institutional admissions, managing stroke in the community, reintegrating into society and adjusting to life after stroke); and reflecting on management to make decisions about self-care. Moreover, they identified problems in all these areas, including inadequate provision of information, poor communication with health-care providers, and unsatisfactory inpatient care.
What Do These Findings Mean?
These findings show that stroke management is extremely demanding for patients and is influenced by both the micro and macro organization of health services. At the micro organizational level, fragmented care and poor communication between patients and clinicians and between health-care providers can mean patients are ill equipped to organize their care and develop coping strategies, which makes adherence to management strategies less likely. At the macro organizational level, it can be hard for patients to obtain the practical and financial help they need to manage their stroke in the community. Overall, these findings suggest that care provision for stroke needs to be transformed so that the needs of patients rather than the needs of health-care systems are prioritized. Further work is required, however, to understand how the patient experience of treatment burden is affected by the clinical characteristics of stroke, by disability level, and by other co-existing diseases. By undertaking such work, it should be possible to generate a patient-reported outcome measure of treatment burden that, if used by policy makers and health-care providers, has the potential to improve the quality of stroke care.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Institute of Neurological Disorders and Stroke provides information about all aspects of stroke (in English and Spanish); its Know Stroke site provides educational materials about stroke prevention, treatment, and rehabilitation including personal stories (in English and Spanish); the US National Institutes of Health SeniorHealth website has additional information about stroke
The Internet Stroke Center provides detailed information about stroke for patients, families, and health professionals (in English and Spanish)
The UK National Health Service Choices website also provides information about stroke for patients and their families, including personal stories
MedlinePlus has links to additional resources about stroke (in English and Spanish)
The UK not-for-profit website Healthtalkonline provides personal stories about stroke
Wikipedia provides information on the burden of treatment and on the normalization process theory (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC3692487  PMID: 23824703
16.  A systematic review of patient-reported measures of burden of treatment in three chronic diseases 
Burden of treatment refers to the workload of health care and its impact on patient functioning and well-being. There are a number of patient-reported measures that assess burden of treatment in single diseases or in specific treatment contexts. A review of such measures could help identify content for a general measure of treatment burden that could be used with patients dealing with multiple chronic conditions. We reviewed the content and psychometric properties of patient-reported measures that assess aspects of treatment burden in three chronic diseases, ie, diabetes, chronic kidney disease, and heart failure.
We searched Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, and EBSCO CINAHL through November 2011. Abstracts were independently reviewed by two people, with disagreements adjudicated by a third person. Retrieved articles were reviewed to confirm relevance, with patient-reported measures scrutinized to determine consistency with the definition of burden of treatment. Descriptive information and psychometric properties were extracted.
A total of 5686 abstracts were identified from the database searches. After abstract review, 359 full-text articles were retrieved, of which 76 met our inclusion criteria. An additional 22 articles were identified from the references of included articles. From the 98 studies, 57 patient-reported measures of treatment burden (full measures or components within measures) were identified. Most were multi-item scales (89%) and assessed treatment burden in diabetes (82%). Only 15 measures were developed using direct patient input and had demonstrable evidence of reliability, scale structure, and multiple forms of validity; six of these demonstrated evidence of sensitivity to change. We identified 12 content domains common across measures and disease types.
Available measures of treatment burden in single diseases can inform derivation of a patient-centered measure of the construct in patients with multiple chronic conditions. Patients should take part in developing the measure to ensure salience and relevance.
PMCID: PMC3699294  PMID: 23833553
patient-reported outcomes; treatment burden; questionnaire; psychometric properties; self-management; patient-centered
17.  Examining health promotion interventions for patients with chronic conditions using a novel patient-centered complexity model: protocol for a systematic review and meta-analysis 
Systematic Reviews  2013;2:29.
Successful chronic care self-management requires adherence to healthy lifestyle behaviors, but many healthcare-based health promotion interventions have resulted in small and unsustainable changes in patient behavior. Patients with chronic conditions may already be overwhelmed by burdensome illnesses and treatments, and not have the capacity to respond well to the additional work required of behavior modifications. To explore this phenomenon, we will apply the cumulative complexity model (CCM), a patient-centered model of patient complexity, to a systematic review and meta-analysis of healthcare-based health behavior interventions.
This systematic review will include randomized trials published between 2002 and 2012 that compared healthcare-based interventions aimed at improving healthy diet and physical activity in community dwelling adult patients with chronic conditions. After extracting study and risk of bias features from each trial, we will classify the interventions according to the conceptual model. We will then use meta-analysis and subgroup analysis to test hypotheses based on the conceptual model.
Healthcare providers need evidence of successful health promoting interventions for patients with chronic conditions who display common behavioral risk factors. To better understand how patients respond to interventions, we will apply the CCM, which accounts for both the capacity of patients with chronic conditions and their treatment-related workload, and posits that a balance between capacity and workload predicts successful enactment of self-care. Analysis will also include whether patients with multiple chronic conditions respond differently to interventions compared to those with single chronic conditions. The results of this review will provide insights as to how patients with chronic conditions respond to health-promoting interventions.
Review registration
PROSPERO registration number: CRD42012003428
PMCID: PMC3655854  PMID: 23663259
Health behavior; Comorbidities; Multimorbidity; Chronic conditions; Patient complexity; Cumulative complexity model; Physical activity; Diet
19.  The Association between Histamine 2 Receptor Antagonist Use and Clostridium difficile Infection: A Systematic Review and Meta-analysis 
PLoS ONE  2013;8(3):e56498.
Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI.
We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI.
Data source
We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI.
Study selection
Two authors independently reviewed the studies for eligibility.
Data extraction
Data about studies characteristics, adjusted effect estimates and quality were extracted.
Data synthesis
Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097).
In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics.
PMCID: PMC3587620  PMID: 23469173
20.  The Role of Statins in Prevention and Treatment of Community Acquired Pneumonia: A Systematic Review and Meta-Analysis 
PLoS ONE  2013;8(1):e52929.
Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications.
Performed a systematic review to address the role of statins in the prevention or treatment of CAP.
Data Source
Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies.
Study Selection
Two authors independently reviewed studies that examined the role of statins in CAP.
Data Extraction
Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted.
Data Synthesis
Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74–0.95), I2 = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59–0.78), I2 = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77–0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder.
Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias.
PMCID: PMC3538683  PMID: 23349694
21.  Association between Proton Pump Inhibitor Therapy and Clostridium difficile Infection: A Contemporary Systematic Review and Meta-Analysis 
PLoS ONE  2012;7(12):e50836.
Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI).
Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings.
We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year.
In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship.
PMCID: PMC3517572  PMID: 23236397
22.  Treatment of hyperprolactinemia: a systematic review and meta-analysis 
Systematic Reviews  2012;1:33.
Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia.
We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels).
After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to −11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists.
Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.
PMCID: PMC3483691  PMID: 22828169
Treatment; Hyperprolactinemia; Macroprolactinoma; Microprolactinoma
23.  The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis 
Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis.
We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data.
35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant.
The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.
Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis
PMCID: PMC3342117  PMID: 22463676
Hypertriglyceridemia; Cardiovascular disease; Pancreatitis; Systematic reviews and meta-analysis
24.  Accuracy and Quality of Clinical Decision Rules for Syncope in the Emergency Department: A Systematic Review and Meta-analysis 
Annals of emergency medicine  2010;56(4):362-373.e1.
We assessed the methodological quality and prognostic accuracy of clinical decision rules (CDR) in emergency department (ED) syncope patients.
We searched 5 electronic databases, reviewed reference lists of included studies and contacted content experts to identify articles for review. Studies that derived or validated CDRs in ED syncope patients were included. Two reviewers independently screened records for relevance, selected studies for inclusion, assessed study quality and abstracted data. Random effects meta-analysis was used to pool diagnostic performance estimates across studies that derived or validated the same CDR. Between study heterogeneity was assessed with I-squared statistic (I2), and subgroup hypotheses were tested using a test of interaction.
We identified 18 eligible studies. Deficiencies in outcome (blinding) and inter-rater reliability assessment were the most common methodological weaknesses. Meta-analysis of the San Francisco Syncope Rule (SFSR) [sensitivity 86% (95%CI 83-89); specificity 49% (95%CI 48-51)] and the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score [sensitivity 95% (95%CI 88-98); specificity 31% (95%CI 29-34)]. Subgroup analysis identified study design [prospective, diagnostic odds ratio (DOR) 8.82 (95%CI 3.5-22) vs. retrospective, DOR 2.45 (95%CI 0.96-6.21)] and ECG determination [by evaluating physician, DOR 25.5 (95%CI 4.41-148) vs. researcher or cardiologist, DOR 4 (95%CI 2.15-7.55)] as potential explanations for the variability in SFSR performance.
The methodological quality and prognostic accuracy of CDRs for syncope is limited. Differences in study design and ECG interpretation may account for the variable prognostic performance of the SFSR when validated in different practice settings.
PMCID: PMC2946941  PMID: 20868906
syncope; clinical decision rules
25.  Factors Influencing Cancer Risk Perception in High Risk Populations: A Systematic Review 
Patients at higher than average risk of heritable cancer may process risk information differently than the general population. However, little is known about clinical, demographic, or psychosocial predictors that may impact risk perception in these groups. The objective of this study was to characterize factors associated with perceived risk of developing cancer in groups at high risk for cancer based on genetics or family history.
We searched Ovid MEDLINE, Ovid Embase, Ovid PsycInfo, and Scopus from inception through April 2009 for English-language, original investigations in humans using core concepts of "risk" and "cancer." We abstracted key information and then further restricted articles dealing with perceived risk of developing cancer due to inherited risk.
Of 1028 titles identified, 53 articles met our criteria. Most (92%) used an observational design and focused on women (70%) with a family history of or contemplating genetic testing for breast cancer. Of the 53 studies, 36 focused on patients who had not had genetic testing for cancer risk, 17 included studies of patients who had undergone genetic testing for cancer risk. Family history of cancer, previous prophylactic tests and treatments, and younger age were associated with cancer risk perception. In addition, beliefs about the preventability and severity of cancer, personality factors such as "monitoring" personality, the ability to process numerical information, as well as distress/worry also were associated with cancer risk perception. Few studies addressed non-breast cancer or risk perception in specific demographic groups (e.g. elderly or minority groups) and few employed theory-driven analytic strategies to decipher interrelationships of factors.
Several factors influence cancer risk perception in patients at elevated risk for cancer. The science of characterizing and improving risk perception in cancer for high risk groups, although evolving, is still relatively undeveloped in several key topic areas including cancers other than breast and in specific populations. Future rigorous risk perception research using experimental designs and focused on cancers other than breast would advance the field.
PMCID: PMC3118965  PMID: 21595959

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