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1.  Optimal case definitions of upper extremity disorder for use in the clinical treatment and referral of patients 
Arthritis care & research  2012;64(4):573-580.
Experts disagree about the optimal classification of upper limb disorders (ULDs). To explore whether differential response to treatments offers a basis for choosing between case definitions, we analysed previously published research.
We screened 183 randomised controlled trials (RCTs) of treatments for ULDs, identified from the bibliographies of 10 Cochrane reviews, four other systematic reviews, and a search in Medline, Embase, and Google Scholar to June 2010. From these, we selected RCTs which allowed estimates of benefit (expressed as relative risks (RRs)) for >1 case definition to be compared when other variables (treatment, comparison group, follow-up time, outcome measure) were effectively held constant. Comparisons of RRs for paired case definitions were summarised by their ratios, with the RR for the simpler and broader definition as the denominator.
Two RCT reports allowed within-trial comparison of RRs and thirteen others allowed between-trial comparisons. Together these provided 17 ratios of RRs (five for shoulder treatments, 12 for elbow treatments, none for wrist/hand treatments). The median ratio of RRs was 1.0 (range 0.3 to 1.7; interquartile range 0.6 to 1.3).
Although the evidence base is limited, our findings suggest that for musculoskeletal disorders of the shoulder and elbow, clinicians in primary care will often do best to apply simpler and broader case definitions. Researchers should routinely publish secondary analyses for subgroups of patients by different diagnostic features at trial entry, to expand the evidence base on optimal case definitions for patient management.
PMCID: PMC3428871  PMID: 22213545
2.  Evaluation of the Pyrrolizidine Alkaloid Induced Liver Disease (PAILD) Active Surveillance System in Tigray, Ethiopia 
To describe the results of the evaluation of the PAILD active surveillance system and lessons learned for similar surveillance efforts in a resource-limited setting.
A liver disease of unknown etiology, called unknown liver disease (ULD) by the community, was first identified in 2002 in Tigray; a rugged, semi-arid, mountainous region that is considered one of the most drought-prone and food insecure regions of Ethiopia. ULD is a chronic condition characterized by epigastric pain, abdominal distention, ascites, emaciation, and hepato/splenomegaly. In 2005, the Ethiopian Health and Nutritional Research Institute was assigned by the Ethiopia Ministry of Health to assist the Tigray Regional Health Bureau and oversee the disease investigation. In 2008, Centers for Disease Control and Prevention (CDC) assisted the Ethiopian team and jointly developed the surveillance tools. The surveillance system was implemented in 2009 with the objectives to determine the magnitude and distribution of the disease; identify disease trends; detect cases to provide them with clinical care; and inform health officials and funding bodies for resource allocation. After several investigations, a local plant containing a particular type of pyrrolizidine alkaloid (PA) toxin that contaminated local foodstuffs was identified as the etiologic agent, and ULD was renamed PAILD in 2011.
From 20 September to 1 October 2011, we conducted site visits, held semi-structured interviews with 20 staff members, reviewed reporting materials, and summarized the information flow including data collection, reporting, analysis, and dissemination.
This surveillance system was implemented in 13 rural, resource-limited districts in the NW, Central and Western Zones. The system identified a total of 1033 cases, including 314 deaths, as of September 2011; guided medication distribution to the health facilities; served as a registry for patient follow up; and provided decision-makers with information needed to allocate resources. A large-scale training was conducted in 2010; however, high staff turnover and a lack of backup surveillance staff at each site suggested that additional training may be needed. Due to the absence of a diagnostic test, the case definition was very simple to enable frontline staff in the communities and at the health posts/centers to identify disease cases. These individuals travelled long distances by foot to deliver paper surveillance forms to the district health offices. A surveillance team placed in the NW Zonal office collected missing reports from the health facilities given limited transportation; however they have left since this evaluation. Information from the surveillance system was shared with partner agencies at the national level every 3 to 6 months; however, this information was not shared with frontline staff.
The PAILD Active Surveillance System met its objectives as originally defined. Evaluation of this unique surveillance system for a chronic disease with unknown cause in a resource-limited setting provides several lessons that can inform similar surveillance efforts. Ongoing logistical challenges (e.g., shortage of paper forms, lack of transportation, and long distances between locations) complicated data collection and reporting. While electronic reporting may have helped overcome some of these difficulties, it was not feasible in this setting. Frontline staff identified cases in the community so that they could receive treatment; these key staff can be further incentivized by receiving regular training and surveillance reports. Ongoing support will be critical to overcome these unique challenges to ensure continual disease monitoring as interventions to disrupt PA exposure are implemented in the community.
PMCID: PMC3692817
Evaluation; Pyrrolizidine Alkaloid Induced Liver Disease; Active Surveillance System; Ethiopia
3.  Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry: A Cross-sectional Study of Common Conditions in the United States 
PLoS Medicine  2013;10(8):e1001500.
Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members' industry ties.
Methods and Findings
We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies.
Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating “pre-disease”; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes.
Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications.
For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies.
Please see later in the article for the Editors' Summary
Editors' Summary
Health professionals generally base their diagnosis of physical and mental disorders among their patients on disease definitions and diagnostic thresholds that are drawn up by expert panels and published as statements or as part of clinical practice guidelines. These disease definitions and diagnostic thresholds are reviewed and updated in response to changes in disease detection methods, treatments, medical knowledge, and, in the case of mental illness, changes in cultural norms. Sometimes, the review process widens disease definitions and lowers diagnostic thresholds. Such changes can be beneficial. For example, they might ensure that life-threatening conditions are diagnosed early when they are still treatable. But the widening of disease definitions can also lead to over-diagnosis—the diagnosis of a condition in a healthy individual that will never cause any symptoms and won't lead to an early death. Over-diagnosis can unnecessarily label people as ill, harm healthy individuals by exposing them to treatments they do not need, and waste resources that could be used to treat or prevent “genuine” illness.
Why Was This Study Done?
In recent years, evidence for widespread financial and non-financial ties between pharmaceutical companies and the health professionals involved in writing clinical practice guidelines has increased, and concern that these links may influence professional judgments has grown. As a result, a 2011 report from the US Institute of Medicine (IOM) recommended that, whenever possible, guideline developers should not have conflicts of interest, that a minority of the panel members involved in guideline development should have conflicts of interest, and that the chairs of these panels should be free of conflicts. Much less is known, however, about the ties between industry and the health professionals involved in reviewing disease definitions and whether these ties might in some way contribute to over-diagnosis. In this cross-sectional study (an investigation that takes a snapshot of a situation at a single time point), the researchers identify panels that have recently made decisions about definitions or diagnostic thresholds for conditions that are common in the US and describe the industry ties among the panel members and the changes in disease definitions proposed by the panels.
What Did the Researchers Do and Find?
The researchers identified 16 publications in which expert panels proposed changes to the disease definitions and diagnostic criteria for 14 conditions that are common in the US such as hypertension (high blood pressure) and Alzheimer disease. The proposed changes widened the disease definition for ten diseases, narrowed it for one disease, and had an unclear impact for five diseases. Reasons included in the publications for changing disease definitions included new evidence of risk for people previously considered normal (pre-hypertension) and the emergence of new biomarkers, tests, or treatments (Alzheimer disease). Only six of the panels mentioned possible harms of the proposed changes and none appeared to rigorously assess the downsides of expanding definitions. Of the 15 panels involved in the publications (one panel produced two publications), 12 included members who disclosed financial ties to multiple companies. Notably, the commonest industrial ties among these panels were to companies marketing drugs for the disease being considered by that panel. On average, 75% of panel members disclosed industry ties (range 0% to 100%) to a median of seven companies each. Moreover, similar proportions of panel members disclosed industry ties in publications released before and after the 2011 IOM report.
What Do These Findings Mean?
These findings show that, for the conditions studied, most panels considering disease definitions and diagnostic criteria proposed changes that widened disease definitions and that financial ties with pharmaceutical companies with direct interests in the therapeutic area covered by the panel were common among panel members. Because this study does not include a comparison group, these findings do not establish a causal link between industry ties and proposals to change disease definitions. Moreover, because the study concentrates on a subset of common diseases in the US setting, the generalizability of these findings is limited. Despite these and other study limitations, these findings provide new information about the ties between industry and influential medical professionals and raise questions about the current processes of disease definition. Future research, the researchers suggest, should investigate how disease definitions change over time, how much money panel members receive from industry, and how panel proposals affect the potential market of sponsors. Finally it should aim to design new processes for reviewing disease definitions that are free from potential conflicts of interest.
Additional Information
Please access these Web sites via the online version of this summary at
A PLOS Medicine Research Article by Knüppel et al. assesses the representation of ethical issues in general clinical practice guidelines on dementia care
Wikipedia has a page on medical diagnosis (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
An article on over-diagnosis by two of the study authors is available; an international conference on preventing over-diagnosis will take place this September
The 2011 US Institute of Medicine report Clinical Practice Guidelines We Can Trust is available
A PLOS Medicine Essay by Lisa Cosgrove and Sheldon Krimsky discusses the financial ties with industry of panel members involved in the preparation of the latest revision of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM), which provides standard criteria for the classification of mental disorders
PMCID: PMC3742441  PMID: 23966841
4.  Stenting for Peripheral Artery Disease of the Lower Extremities 
Executive Summary
In January 2010, the Medical Advisory Secretariat received an application from University Health Network to provide an evidentiary platform on stenting as a treatment management for peripheral artery disease. The purpose of this health technology assessment is to examine the effectiveness of primary stenting as a treatment management for peripheral artery disease of the lower extremities.
Clinical Need: Condition and Target Population
Peripheral artery disease (PAD) is a progressive disease occurring as a result of plaque accumulation (atherosclerosis) in the arterial system that carries blood to the extremities (arms and legs) as well as vital organs. The vessels that are most affected by PAD are the arteries of the lower extremities, the aorta, the visceral arterial branches, the carotid arteries and the arteries of the upper limbs. In the lower extremities, PAD affects three major arterial segments i) aortic-iliac, ii) femoro-popliteal (FP) and iii) infra-popliteal (primarily tibial) arteries. The disease is commonly classified clinically as asymptomatic claudication, rest pain and critical ischemia.
Although the prevalence of PAD in Canada is not known, it is estimated that 800,000 Canadians have PAD. The 2007 Trans Atlantic Intersociety Consensus (TASC) II Working Group for the Management of Peripheral Disease estimated that the prevalence of PAD in Europe and North America to be 27 million, of whom 88,000 are hospitalizations involving lower extremities. A higher prevalence of PAD among elderly individuals has been reported to range from 12% to 29%. The National Health and Nutrition Examination Survey (NHANES) estimated that the prevalence of PAD is 14.5% among individuals 70 years of age and over.
Modifiable and non-modifiable risk factors associated with PAD include advanced age, male gender, family history, smoking, diabetes, hypertension and hyperlipidemia. PAD is a strong predictor of myocardial infarction (MI), stroke and cardiovascular death. Annually, approximately 10% of ischemic cardiovascular and cerebrovascular events can be attributed to the progression of PAD. Compared with patients without PAD, the 10-year risk of all-cause mortality is 3-fold higher in patients with PAD with 4-5 times greater risk of dying from cardiovascular event. The risk of coronary heart disease is 6 times greater and increases 15-fold in patients with advanced or severe PAD. Among subjects with diabetes, the risk of PAD is often severe and associated with extensive arterial calcification. In these patients the risk of PAD increases two to four fold. The results of the Canadian public survey of knowledge of PAD demonstrated that Canadians are unaware of the morbidity and mortality associated with PAD. Despite its prevalence and cardiovascular risk implications, only 25% of PAD patients are undergoing treatment.
The diagnosis of PAD is difficult as most patients remain asymptomatic for many years. Symptoms do not present until there is at least 50% narrowing of an artery. In the general population, only 10% of persons with PAD have classic symptoms of claudication, 40% do not complain of leg pain, while the remaining 50% have a variety of leg symptoms different from classic claudication. The severity of symptoms depends on the degree of stenosis. The need to intervene is more urgent in patients with limb threatening ischemia as manifested by night pain, rest pain, ischemic ulcers or gangrene. Without successful revascularization those with critical ischemia have a limb loss (amputation) rate of 80-90% in one year.
Diagnosis of PAD is generally non-invasive and can be performed in the physician offices or on an outpatient basis in a hospital. Most common diagnostic procedure include: 1) Ankle Brachial Index (ABI), a ratio of the blood pressure readings between the highest ankle pressure and the highest brachial (arm) pressure; and 2) Doppler ultrasonography, a diagnostic imaging procedure that uses a combination of ultrasound and wave form recordings to evaluate arterial flow in blood vessels. The value of the ABI can provide an assessment of the severity of the disease. Other non invasive imaging techniques include: Computed Tomography (CT) and Magnetic Resonance Angiography (MRA). Definitive diagnosis of PAD can be made by an invasive catheter based angiography procedure which shows the roadmap of the arteries, depicting the exact location and length of the stenosis / occlusion. Angiography is the standard method against which all other imaging procedures are compared for accuracy.
More than 70% of the patients diagnosed with PAD remain stable or improve with conservative management of pharmacologic agents and life style modifications. Significant PAD symptoms are well known to negatively influence an individual quality of life. For those who do not improve, revascularization methods either invasive or non-invasive can be used to restore peripheral circulation.
Technology Under Review
A Stent is a wire mesh “scaffold” that is permanently implanted in the artery to keep the artery open and can be combined with angioplasty to treat PAD. There are two types of stents: i) balloon-expandable and ii) self expandable stents and are available in varying length. The former uses an angioplasty balloon to expand and set the stent within the arterial segment. Recently, drug-eluting stents have been developed and these types of stents release small amounts of medication intended to reduce neointimal hyperplasia, which can cause re-stenosis at the stent site. Endovascular stenting avoids the problem of early elastic recoil, residual stenosis and flow limiting dissection after balloon angioplasty.
Research Questions
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), is primary stenting more effective than percutaneous transluminal angioplasty (PTA) in improving patency?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), does primary stenting provide immediate success compared to PTA?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), is primary stenting associated with less complications compared to PTA?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion), does primary stenting compared to PTA reduce the rate of re-intervention?
In individuals with PAD of the lower extremities (superficial femoral artery, infra-popliteal, crural and iliac artery stenosis or occlusion) is primary stenting more effective than PTA in improving clinical and hemodynamic success?
Are drug eluting stents more effective than bare stents in improving patency, reducing rates of re-interventions or complications?
Research Methods
Literature Search
A literature search was performed on February 2, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA). Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
English language full-reports from 1950 to January Week 3, 2010
Comparative randomized controlled trials (RCTs), systematic reviews and meta-analyses of RCTs
Proven diagnosis of PAD of the lower extremities in all patients.
Adult patients at least 18 years of age.
Stent as at least one treatment arm.
Patency, re-stenosis, re-intervention, technical success, hemodynamic (ABI) and clinical improvement and complications as at least an outcome.
Exclusion Criteria
Non-randomized studies
Observational studies (cohort or retrospective studies) and case report
Feasibility studies
Studies that have evaluated stent but not as a primary intervention
Outcomes of Interest
The primary outcome measure was patency. Secondary measures included technical success, re-intervention, complications, hemodynamic (ankle brachial pressure index, treadmill walking distance) and clinical success or improvement according to Rutherford scale. It was anticipated, a priori, that there would be substantial differences among trials regarding the method of examination and definitions of patency or re-stenosis. Where studies reported only re-stenosis rates, patency rates were calculated as 1 minus re-stenosis rates.
Statistical Analysis
Odds ratios (for binary outcomes) or mean difference (for continuous outcomes) with 95% confidence intervals (CI) were calculated for each endpoint. An intention to treat principle (ITT) was used, with the total number of patients randomized to each study arm as the denominator for each proportion. Sensitivity analysis was performed using per protocol approach. A pooled odds ratio (POR) or mean difference for each endpoint was then calculated for all trials reporting that endpoint using a fixed effects model. PORs were calculated for comparisons of primary stenting versus PTA or other alternative procedures. Level of significance was set at alpha=0.05. Homogeneity was assessed using the chi-square test, I2 and by visual inspection of forest plots. If heterogeneity was encountered within groups (P < 0.10), a random effects model was used. All statistical analyses were performed using RevMan 5. Where sufficient data were available, these analyses were repeated within subgroups of patients defined by time of outcome assessment to evaluate sustainability of treatment benefit. Results were pooled based on the diseased artery and stent type.
Summary of Findings
Balloon-expandable stents vs PTA in superficial femoral artery disease
Based on a moderate quality of evidence, there is no significant difference in patency between primary stenting using balloon-expandable bare metal stents and PTA at 6, 12 and 24 months in patients with superficial femoral artery disease. The pooled OR for patency and their corresponding 95% CI are: 6 months 1.26 (0.74, 2.13); 12 months 0.95 (0.66, 1.38); and 24 months 0.72 (0.34. 1.55).
There is no significant difference in clinical improvement, re-interventions, peri and post operative complications, mortality and amputations between primary stenting using balloon-expandable bare stents and PTA in patients with superficial femoral artery. The pooled OR and their corresponding 95% CI are clinical improvement 0.85 (0.50, 1.42); ankle brachial index 0.01 (-0.02, 0.04) re-intervention 0.83 (0.26, 2.65); complications 0.73 (0.43, 1.22); all cause mortality 1.08 (0.59, 1.97) and amputation rates 0.41 (0.14, 1.18).
Self-expandable stents vs PTA in superficial femoral artery disease
Based on a moderate quality of evidence, primary stenting using self-expandable bare metal stents is associated with significant improvement in patency at 6, 12 and 24 months in patients with superficial femoral artery disease. The pooled OR for patency and their corresponding 95% CI are: 6 months 2.35 (1.06, 5.23); 12 months 1.54 (1.01, 2.35); and 24 months 2.18 (1.00. 4.78). However, the benefit of primary stenting is not observed for clinical improvement, re-interventions, peri and post operative complications, mortality and amputation in patients with superficial femoral artery disease. The pooled OR and their corresponding 95% CI are clinical improvement 0.61 (0.37, 1.01); ankle brachial index 0.01 (-0.06, 0.08) re-intervention 0.60 (0.36, 1.02); complications 1.60 (0.53, 4.85); all cause mortality 3.84 (0.74, 19.22) and amputation rates 1.96 (0.20, 18.86).
Balloon expandable stents vs PTA in iliac artery occlusive disease
Based on moderate quality of evidence, despite immediate technical success, 12.23 (7.17, 20.88), primary stenting is not associated with significant improvement in patency, clinical status, treadmill walking distance and reduction in re-intervention, complications, cardiovascular events, all cause mortality, QoL and amputation rates in patients with intermittent claudication caused by iliac artery occlusive disease. The pooled OR and their corresponding 95% CI are: patency 1.03 (0.56, 1.87); clinical improvement 1.08 (0.60, 1.94); walking distance 3.00 (12.96, 18.96); re-intervention 1.16 (0.71, 1.90); complications 0.56 (0.20, 1.53); all cause mortality 0.89 (0.47, 1.71); QoL 0.40 (-4.42, 5.52); cardiovascular event 1.16 (0.56, 2.40) and amputation rates 0.37 (0.11, 1.23). To date no RCTs are available evaluating self-expandable stents in the common or external iliac artery stenosis or occlusion.
Drug-eluting stent vs balloon-expandable bare metal stents in crural arteries
Based on a very low quality of evidence, at 6 months of follow-up, sirolimus drug-eluting stents are associated with a reduction in target vessel revascularization and re-stenosis rates in patients with atherosclerotic lesions of crural (tibial) arteries compared with balloon-expandable bare metal stent. The OR and their corresponding 95% CI are: re-stenosis 0.09 (0.03, 0.28) and TVR 0.15 (0.05, 0.47) in patients with atherosclerotic lesions of the crural arteries at 6 months follow-up. Both types of stents offer similar immediate success. Limitations of this study include: short follow-up period, small sample and no assessment of mortality as an outcome. Further research is needed to confirm its effect and safety.
PMCID: PMC3377569  PMID: 23074395
5.  Surveillance case definitions for work related upper limb pain syndromes 
OBJECTIVES: To establish consensus case definitions for several common work related upper limb pain syndromes for use in surveillance or studies of the aetiology of these conditions. METHODS: A group of healthcare professionals from the disciplines interested in the prevention and management of upper limb disorders were recruited for a Delphi exercise. A questionnaire was used to establish case definitions from the participants, followed by a consensus conference involving the core group of 29 people. The draft conclusions were recirculated for review. RESULTS: Consensus case definitions were agreed for carpal tunnel syndrome, tenosynovitis of the wrist, de Quervain's disease of the wrist, epicondylitis, shoulder capsulitis (frozen shoulder), and shoulder tendonitis. The consensus group also identified a condition defined as "non-specific diffuse forearm pain" although this is essentially a diagnosis made by exclusion. The group did not have enough experience of the thoracic outlet syndrome to make recommendations. CONCLUSIONS: There was enough consensus between several health professionals from different disciplines to establish case definitions suitable for use in the studies of several work related upper limb pain syndromes. The use of these criteria should allow comparability between studies and centres and facilitate research in this field. The criteria may also be useful in surveillance programmes and as aids to case management.
PMCID: PMC1757569  PMID: 9624281
6.  Cutaneous melanoma: hints from occupational risks by anatomic site in Swedish men 
Aims: To improve knowledge of the epidemiology of melanoma by comparing occupational risks of cutaneous melanoma (CM) by anatomic site in Swedish workers.
Methods: Male workers employed in 1970 and living in the country in 1960 were followed up from 1971 to 1989 using the Swedish Registers of Death and Cancer. A more specifically exposed subcohort included men reporting the same occupation in 1960 and 1970. For each location, occupational risk ratios (RRs) were extracted from Poisson regression models adjusted by age, period, town size, and geographical area. To diminish the influence of socioeconomic factors, intrasector analyses, comparing only jobs belonging to the same occupational sector, were performed. Risk patterns for different locations were compared.
Results: High RRs for different sites were found among workers exposed to UV sources (dentists, physiotherapists, and lithographers), and sun exposed workers (harbour masters, and lighthouse/related work). Risk excesses were seen in fur tailors, tanners/fur dressers, patternmakers/cutters, electrical fitters/wiremen, telephone/telegraph installers/repairmen, and some glass/pottery/tile workers. Results for lower and upper limbs were significantly correlated but somewhat independent of those found in thorax, the most frequent location. Correlation between head/neck and thorax was moderate. Specific risk excesses were found for rolling mill workers in head/neck, for chimney sweeps in upper limbs, and for aircraft pilots/navigators/flight engineers in lower limbs.
Conclusions: High RRs in the trunk among occupations with UV exposure from artificial sources suggest an effect not restricted to exposed sites. An unusual distribution of cases and RRs in chimney sweeps, rolling-mill, or glass/pottery/tile workers suggests local effects of exposures. The not previously reported risk excess in this job and in fur related processes, and the RR in electrical fitters and telephone/telegraph installers deserve further investigation. Disparities between locations, as RRs in thorax and limbs, may reflect differences in aetiological mechanisms.
PMCID: PMC1740709  PMID: 14739377
7.  Systematic review and assessment of validated case definitions for depression in administrative data 
BMC Psychiatry  2014;14(1):289.
Administrative data are increasingly used to conduct research on depression and inform health services and health policy. Depression surveillance using administrative data is an alternative to surveys, which can be more resource-intensive. The objectives of this study were to: (1) systematically review the literature on validated case definitions to identify depression using International Classification of Disease and Related Health Problems (ICD) codes in administrative data and (2) identify individuals with and without depression in administrative data and develop an enhanced case definition to identify persons with depression in ICD-coded hospital data.
(1) Systematic review: We identified validation studies using ICD codes to indicate depression in administrative data up to January 2013. (2) Validation: All depression case definitions from the literature and an additional three ICD-9-CM and three ICD-10 enhanced definitions were tested in an inpatient database. The diagnostic accuracy of all case definitions was calculated [sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV)].
(1) Systematic review: Of 2,014 abstracts identified, 36 underwent full-text review and three met eligibility criteria. These depression studies used ICD-9 and ICD-10 case definitions. (2) Validation: 4,008 randomly selected medical charts were reviewed to assess the performance of new and previously published depression-related ICD case definitions. All newly tested case definitions resulted in Sp >99%, PPV >89% and NPV >91%. Sensitivities were low (28-35%), but higher than for case definitions identified in the literature (1.1-29.6%).
Validating ICD-coded data for depression is important due to variation in coding practices across jurisdictions. The most suitable case definitions for detecting depression in administrative data vary depending on the context. For surveillance purposes, the most inclusive ICD-9 & ICD-10 case definitions resulted in PPVs of 89.7% and 89.5%, respectively. In cases where diagnostic certainty is required, the least inclusive ICD-9 and −10 case definitions are recommended, resulting in PPVs of 92.0% and 91.1%. All proposed case definitions resulted in suboptimal levels of sensitivity (ranging from 28.9%-35.6%). The addition of outpatient data (such as pharmacy records) for depression surveillance is recommended and should result in improved measures of validity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12888-014-0289-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4201696  PMID: 25322690
Depression; Validation; Systematic review; Administrative data; International Classification of Diseases
8.  Noise Reduction and Image Quality Improvement of Low Dose and Ultra Low Dose Brain Perfusion CT by HYPR-LR Processing 
PLoS ONE  2011;6(2):e17098.
To evaluate image quality and signal characteristics of brain perfusion CT (BPCT) obtained by low-dose (LD) and ultra-low-dose (ULD) protocols with and without post-processing by highly constrained back-projection (HYPR)–local reconstruction (LR) technique.
Methods and Materials
Simultaneous BPCTs were acquired in 8 patients on a dual-source-CT by applying LD (80 kV,200 mAs,14×1.2 mm) on tube A and ULD (80 kV,30 mAs,14×1.2 mm) on tube B. Image data from both tubes was reconstructed with identical parameters and post-processed using the HYPR-LR. Correlation coefficients between mean and maximum (MAX) attenuation values within corresponding ROIs, area under attenuation curve (AUC), and signal to noise ratio (SNR) of brain parenchyma were assessed. Subjective image quality was assessed on a 5-point scale by two blinded observers (1:excellent, 5:non-diagnostic).
Radiation dose of ULD was more than six times lower compared to LD. SNR was improved by HYPR: ULD vs. ULD+HYPR: 1.9±0.3 vs. 8.4±1.7, LD vs. LD+HYPR: 5.0±0.7 vs. 13.4±2.4 (both p<0.0001). There was a good correlation between the original datasets and the HYPR-LR post-processed datasets: r = 0.848 for ULD and ULD+HYPR and r = 0.933 for LD and LD+HYPR (p<0.0001 for both). The mean values of the HYPR-LR post-processed ULD dataset correlated better with the standard LD dataset (r = 0.672) than unprocessed ULD (r = 0.542), but both correlations were significant (p<0.0001). There was no significant difference in AUC or MAX. Image quality was rated excellent (1.3) in LD+HYPR and non-diagnostic (5.0) in ULD. LD and ULD+HYPR images had moderate image quality (3.3 and 2.7).
SNR and image quality of ULD-BPCT can be improved to a level similar to LD-BPCT when using HYPR-LR without distorting attenuation measurements. This can be used to substantially reduce radiation dose. Alternatively, LD images can be improved by HYPR-LR to higher diagnostic quality.
PMCID: PMC3037968  PMID: 21347259
9.  Work-related Musculoskeletal Disorders in Korea and Japan: A Comparative Description 
Work related Musculoskeletal disorders (WMSD) is one of the most important problem in occupational health system of Korea and Japan, where the OHS system developed in similar socio-cultural environment. This study compared WMSD in Korea and Japan to review similarities and differences in their historical background, and development of prevention policies.
Scientific articles, government reports, and related official and non-official statistics on WMSD since the 1960s in Japan and Korea were reviewed.
The historical background and basic structure of the compensation system in Korea and Japan largely overlapped. The issuing of WMSD in both countries appeared as upper limb disorder (ULD), named occupational cervicobrachial diseases (OCD) in Japan, and neck-shoulder-arm syndrome (NSA) 30 years later in Korea, following the change from an industrial structure to automated office work. Both countries developed manuals for diagnosis, guidelines for workplace management, and prevention policies. At present, compensation cases per covered insurers for WMSD are higher in Korea than in Japan, due to the social welfare system and cultural environment. Prevention policies in Korea are enforced more strongly with punitive measures than in Japan. In contrast, the Japanese system requires autonomous effort toward risk control and management, focusing on specific risky processes.
WMSD in Korea and Japan have a similar history of identification and compensation structure, yet different compensation proportions per covered insurer and prevention policies. Follow-up study with international cooperation is necessary to improve both systems.
PMCID: PMC4096546  PMID: 25024844
Musculoskeletal disorders; Work-related; Korea; Japan; Comparative review
10.  Methods for injury surveillance in international cricket 
Background: The varying methods of cricket injury surveillance have made direct comparison of published studies in this field impossible.
Methods: A consensus regarding definitions and methods to calculate injury rates in cricket was sought between researchers in this field. This was arrived at through a variety of face to face meetings, email communication, and draft reviews between researchers from six of the major cricket playing nations.
Results: It is recommended that a cricket injury is defined as any injury or other medical condition that either (a) prevents a player from being fully available for selection for a major match or (b) during a major match, causes a player to be unable to bat, bowl, or keep wicket when required by either the rules or the team's captain. Recommended definitions for injury incidence (for matches, training sessions, and seasons) and injury prevalence are also provided. It is proposed that match injury incidence is calculated using a denominator based on a standard time estimated for player exposure in matches, for the purposes of simplicity. This will allow all injury surveillance systems, including those with limited resources, to make calculations according to a standard definition.
Conclusion: The consensus statement presented provides a standard which, if followed, allows meaningful comparison of injury surveillance data from different countries and time periods, which will assist in the possible identification of risk factors for injury in cricket.
PMCID: PMC1725193  PMID: 15793080
11.  Contact Sport Concussion Incidence 
Journal of Athletic Training  2006;41(4):470-472.
Reference/Citation: Koh JO, Cassidy JD, Watkinson EJ. Incidence of concussion in contact sports: a systematic review of the evidence. Brain Inj.20031790191712963556.
Clinical Question: What is the incidence of concussion in various contact sports?
Data Sources: Studies for the review were found through a MEDLINE search (1985–2000) and by gathering and reviewing older articles referenced in the searched articles. The main terms that were included in the search were brain injuries, brain concussion, and incidence. Text words that were also included were mild traumatic brain injury, concussion, incidence, injury, and head injury, along with the names of 8 contact sports ( American football, boxing, ice hockey, judo, karate, tae kwon do, rugby, and soccer).
Study Selection: For this review, concussion was defined as “a mild brain injury resulting from a direct blow to the head resulting in physiological changes in brain function.” Cohort studies with documented incidence of concussion in athletes from 8 identified contact sports were the target of the search. All studies of male and female athletes in any of the 8 contact sports, including practices and games and regardless of level of competition, were included in the study search. Possible articles for review were identified through a 3-step screening process. Article titles were initially screened by one of the authors. If the title seemed to be relevant to the purpose of the review, the abstract of the article was then screened for inclusion/exclusion criteria as the second step. To be included, studies had to relate to the incidence of injury to the head and brain, report results relevant to concussion, involve 1 of the 8 identified contact sports, and be published between 1985 and 2000. All systematic reviews about mild traumatic brain injury (TBI) or concussion were also included. Studies were excluded if they discussed concussion due to whiplash injury or concussion associated with spinal cord injury, facial bone fracture, or soft tissue injuries; if they reported prevalence, rather than incidence, of concussion; if they addressed chronic TBI; if they comprised case reports or letters to the editor; or if they lacked a denominator to determine risk rates. Finally, relevant and unknown articles from the abstract screening were reviewed again for the inclusion and exclusion criteria by an independent, outside party.
Data Extraction: A general methodologic criteria design was used to critically appraise all articles that met the inclusion and exclusion criteria. This design appraised 11 study design and reporting criteria. In order for an article to be accepted into the systematic review, it had to meet at least the 5 mandatory criteria: description of the source population, appropriate description of inclusion and exclusion criteria, verifiable results from the raw data, differentiation of the incidence of injury between practice and game settings, and adequately measured denominator of population or person-time at risk. For each individual study, the 5 mandatory criteria listed above were rated with regard to whether they were included or addressed in the paper ( yes), were missing from the paper ( no), or were included but not described fully or in a way characterized by sound quality ( substandard). If any of the 5 mandatory criteria were rated no, the article was not evaluated any further. Data taken from these articles included sex, types of sessions in which concussion occurred, and numbers defining incidence of concussion within a contact sport. In some studies, rates were recalculated from the raw data in order to check accuracy, or if they were not presented in the published material, rates were calculated. These rates were recalculated with the denominator presented in the original study, athletes at risk for injury or time at risk for injury. Athlete-exposure was not defined in the review but is commonly used as the denominator in epidemiologic studies and represents one time in which an athlete takes part in a game or practice that exposes him or her to a risk for injury.
Main Results: The overall search identified 559 publications with possible relevance to the incidence of concussion in contact sports. After the titles were screened, 213 articles remained, and their abstracts were reviewed. The abstract screening for relevance yielded 127 articles to which the inclusion and exclusion criteria were applied. The investigators then critically reviewed 63 articles that fit the inclusion criteria. During this critical review, 40 articles did not meet the 5 mandatory criteria listed above and were not evaluated further. After final screening, 23 articles were included in the study. Review of these 23 articles revealed that among team sports for high school males, ice hockey athletes demonstrated the highest incidence of concussion (3.6 per 1000 athlete-exposures [AEs], 95% confidence interval [CI] = 0.99–9.29) and soccer athletes the lowest incidence of concussion (0.18 per 1000 AEs, 95% CI = 0.14–0.22). At the professional level, similar concussion incidence rates were found in both ice hockey (6.5 per 1000 player-games, 95% CI = 4.8–8.6) and rugby (9.05 per 1000 player-games, 95% CI = 4.1–17.1) players. When compared with other individual male sports (karate and tae kwon do), boxing had the highest incidence of concussion in professional (0.8 per 10 rounds, 95% CI = 0.75–0.95) and amateur (7.9 per 1000 man-minutes, 95% CI = 5.45–11.09) athletes. Only 6 included studies (5 dealing with tae kwon do and 1 with soccer) addressed concussion incidence in females. Tae kwon do had the highest incidence of concussion (8.77 per 1000 AEs, 95% CI = 0.22–47.9).
Conclusions: The information presented in the article offers helpful insight into the rate of concussion in athletes from 8 contact sports. Ice hockey seemed to have the greatest incidence of concussion for males, whereas tae kwon do had the highest incidence rate for females. Relatively few rigorous epidemiologic studies on the incidence of concussion exist. Specifically, 63% of the identified studies did not meet the methodologic criteria to be included in this systematic review. In addition, limited information exists on the risk of concussion for females in contact sports. Future authors should address the limitations in reporting incidences, including the lack of adequately measured denominators (person-time at risk), vague definitions of concussion, combining game and practice injuries, and history of concussive injury. Future researchers should also include at least the 5 mandatory methodologic criteria used in the critical appraisal of articles for this review to allow for better reporting of concussion incidence and comparison among various studies. Concussion incidence in females should also be explored.
PMCID: PMC1748409  PMID: 17273475
head injury; brain injury; epidemiology
12.  A Novel Syndrome Definition Validation Approach for Rarely Occurring Diseases 
To develop and test a novel syndrome definition validation approach for rarely occurring diseases.
Early detection of rarely occurring but potentially harmful diseases such as bio-threat agents (e.g., anthrax), chemical agents (e.g., sarin), and naturally occurring diseases (e.g., meningitis) is critical for rapid initiation of treatment, infection control measures, and emergency response plans. To facilitate clinicians’ ability to detect these diseases, various syndrome definitions have been developed. Due to the rarity of these diseases, standard statistical methodologies for validating syndrome definitions are not applicable.
Syndrome definitions were developed by researchers for the Geographic Utilization of Artificial Intelligence in Real-Time for Disease Identification and Alert Notification (GUARDIAN) surveillance system (1). The main steps for validation of the syndrome definitions were: Partition of literature articles: Literature articles that described positive cases were randomly divided to generate detection (75% of articles) and testing (25% of articles) syndrome definitions.Synthetic case generation: Syndrome definitions and associated statistical measures were reverse engineered using probability of occurrence and inverse Gaussian function to generate potentially infinite positive artificial cases.Clinical filter application: To avoid clinically incompatible combinations of newly generated symptoms, rules based on clinically guided knowledge from emergency department (ED) physicians were applied. Steps 2 and 3 were repeated for both detection and testing syndrome definitions.Detection phase validation: ED negative case sample: Detection syndrome definitions were tested using a random sample of negative ED cases. Knowledge gained through false positive cases was utilized to modify the surveillance algorithms and system thresholds.10-fold cross-validation: Standard 10-fold cross-validation on detection articles of positive cases and ED negative cases was utilized to generate performance metrics. Suspected cases were reviewed by ED clinicians for threshold enhancement.Literature articles (n=1): The ability of syndrome definitions to correctly flag literature articles with n=1 case was documented.Testing phase validation: Testing sample: Synthetic positive cases generated from the testing articles along with another set of ED negative cases were evaluated by the respective syndrome definition. Suspected cases were clinically evaluated.Literature articles (n=1): Similar to detection step 4c, articles with n=1 were tested using syndrome definitions.True positive samples: When available, true positive cases from an ED were identified and sent through the GUARDIAN system.Multi-syndrome validation: A combined sample of positive cases of multiple syndromes and ED negative cases were evaluated for detection of individual syndromes among other similar syndromes.
To demonstrate the validation approach, the anthrax syndrome definition was utilized. This syndrome definition was developed with 25 articles containing positive anthrax cases used for detection, and the remaining 11 articles used for testing. With a 10-fold cross validation of the detection phase, the initial results showed accuracy was 99.4% (false positive rate of 0.65% and false negative rate of 0.00%). The testing phase initial validation revealed 99.2% accuracy for the anthrax syndrome definition.
Syndrome specific synthetic samples that are validated through clinical filters allowed the generation of an unlimited number of positive cases. Correct identification by GUARDIAN of these cases indicates robust and reliable syndrome definitions. Utilization of these cases, in conjunction with adherence to a methodological process, was the cornerstone of the GUARDIAN syndrome definition validation approach. The validation approach was successfully demonstrated on anthrax and can be applied to other bio-threat agents, chemical agents, and naturally occurring diseases.
PMCID: PMC3692924
syndromic surveillance; bioterrorism; infectious diseases
13.  Occupational risk factors for female breast cancer: a review. 
OBJECTIVES: Although progress has been made in identifying personal risk factors and in improving treatment for female breast cancer, incidence rates continue to increase. With women now occupying a sizable fraction of the workforce, it is worth inquiring whether there are occupational risk factors for breast cancer. This is a review of occupational studies on female breast cancer. METHODS: Suitable reports and published articles with associations of female breast cancer and occupation were identified from technical reports, by searching the MEDLINE bibliographic data base, and by reviewing each paper on cancer that was published in 20 major journals during the period from about 1971-94. RESULTS: A total of 115 studies were identified; 19 studies relied exclusively on data collected for administrative purposes, and there were four incident case-control studies and 92 cohort studies. Although data for individual industries, occupations, and exposures were sparse, there was limited evidence of an association with employment in the pharmaceutical industry and among cosmetologists and beauticians. Associations were also found for chemists and occupations with possible exposure to extremely low frequency electromagnetic fields, but potential methodological weaknesses preclude drawing any definite conclusions. There was little support for increased risks among textiles workers, dry cleaning workers, and nuclear industry workers. CONCLUSIONS: Few high quality occupational studies directed specifically toward women have been carried out to allow the unambiguous identification of occupational risk factors for breast cancer. It is suggested that investigations that account for non-occupational risk factors and that assess exposure in a more detailed way be carried out. One strategy already suggested is to conduct population based, case-control studies in which subjects are interviewed about their occupational histories and exposure to chemical and physical agents which are then attributed from the job descriptions by a team of experts. These studies can then be supplemented when necessary with cohort studies of specific populations.
PMCID: PMC1128436  PMID: 8704854
14.  Evaluating Utility of Cold-Injury Syndromic Surveillance Data in New York City 
1) Develop cold exposure-related injury syndromic case definitions 2) use historical data to compare trends among cases identified in syndromic surveillance and cases identified in NY Statewide Planning and Research Cooperative System (SPARCS) hospital discharge data to evaluate representativeness and 3) develop regression models to examine relationships with cold weather conditions, and compare relationships across case definitions and data sources.
Cold weather exposure-related injuries range from hypothermia to less severe conditions such as frost bite, trench foot, and chilblains, which are all preventable causes of mortality and morbidity. In recent years, NYC has successfully used syndromic surveillance of heat-related ED visits to inform emergency response during heat waves. Similar timely surveillance of cold-exposure related injuries could also inform public health protection measures during severe winter weather or cold season power outages. We conducted a retrospective analysis to compare hypothermia and cold-injury patient case characteristics, as well as temporal and meteorological correlates, between syndromic surveillance data and hospital discharge data.
Using chief complaint key words, we developed syndromic case definitions for 1) hypothermia only and 2) all injury caused by environmental cold exposure. Case definitions were applied to an archive of 2008–2010 cold season (October to April) syndromic surveillance data reported from a subset of NYC emergency departments (ED SS), representing 95% of all ED visits in NYC. Relevant ICD-9 codes (991, E901.0, E901.8, E901.9, E988.3) were applied to ED discharge data (ED Dx) to detect hypothermia and cold injury cases. Age, gender, and alcohol involvement were compared using tests of proportion to determine whether characteristics of cases identified through ED SS were representative of cases identified in ED Dx data. Poisson regression models were fit to estimate the relation of daily ED SS and Dx counts with daily temperature, snow depth, and other weather conditions. Models were adjusted for month, holiday, day of week, and year to account for potential temporal confounding.
Fewer hypothermia and cold injury cases were detected with ED SS than with ED Dx but the two populations did not differ significantly with respect to age and sex. From 2008–2010, there were 292 hypothermia cases with an average annual rate of 1.2 per 100,000 people, and 445 cold injury cases (1.8 per 100,000) identified in ED SS data. Over the same time period, there were 566 hypothermia cases (2.3 per 100,000) and 933 cold injury cases (3.7 per 100,000) identified in ED Dx data. Daily counts of hypothermia and cold injury were correlated across data sources. In preliminary analyses using both case definitions, minimum daily temperature was associated with increases in daily ED SS and ED Dx counts. Mean daily snow depth was associated with ED SS and ED Dx cold injury cases, although not with hypothermia counts. Risk increased at lower temperatures for both case definitions.
There were no meaningful differences between ED SS and ED Dx weather models. Minimum temperature is associated with both case definitions. Snow depth is associated with cold injury. Daily minimum temperature and mean snow depth are potentially useful in determining timing of surveillance. Syndromic surveillance data are a timely means for monitoring hypothermia and other cold-related injuries, and could provide health departments with useful information during severe winter weather to guide prevention.
PMCID: PMC3692768
syndromic; cold-injury; environmental surveillance
15.  Mesothelioma Register 1967-68 
Greenberg, M., and Lloyd Davies, T. A. (1974).British Journal of Industrial Medicine,31, 91-104. Mesothelioma Register 1967-68. A register of mesothelioma cases is maintained by the Department of Employment, Medical Services Division (now Employment Medical Advisory Service). This paper describes an investigation of 413 notifications to the Register in 1967-68 from England and Wales and Scotland.
Cases were regarded as `definite' when histological confirmation of diagnosis had been obtained, either by hospital pathologists, or by the UICC Panel of Pathologists, to whom pathological material was submitted whenever possible. Two hundred and forty-six cases were accepted as `definite' and 76 cases were regarded as `definitely not' mesothelioma. The remainder were classified as `undecided' or `insufficient pathological material'. Thirty-five of the 76 cases definitely not mesothelioma had nevertheless been so described on death certificates.
The investigation carried out covers clinical aspects, survival, and evidence of exposure to asbestos. Twelve per cent of definite mesotheliomata were of peritoneal origin. The age range was 21 to 87 years, but, in general, mesothelioma occured at an earlier age than `carcinoma of bronchus and lung' or `all malignant tumours' in the Registrar General's statistical mortality tables.
Concomitant asbestosis and the finding of asbestos bodies or pleural plaques occured as frequently in those cases classified as definitely not mesothelioma as in confirmed cases.
Occupational exposure to asbestos was found in 68% of definite cases, apparently significantly more frequently than in those definitely not mesothelioma, but there was observer bias. The interval between the first exposure and death from mesothelioma exceeded 25 years in 85% of cases but was only three and a half years in one case. The duration of exposure varied widely: in 12% of cases it was under five years. The type of asbestos could be ascertained in so few cases that it was impossible to asses the rôle of crocidolite in aetiology. There were 38 definite cases in which no history of any exposure to asbestos could be obtained.
Definite mesotheliomata showed marked clustering in areas where there is substantial industrial use of asbestos. Whether this should be interpreted as evidence of causation or an effect of heightened awareness in these areas cannot be deduced from this study. Evidence is quoted suggesting that the observed annual incidence of approximately 120 definite mesotheliomata in England, Scotland, and Wales may considerably understate the true prevalence.
PMCID: PMC1009563  PMID: 4830768
16.  Epidemiological and quantitative relationships between mesothelioma and asbestos on Tyneside 
Journal of Clinical Pathology  1973;26(11):832-840.
Thirty-five necropsied cases of diffuse malignant mesothelioma of pleura and six cases of mesothelioma of peritoneum are reported. Occupational histories from 40 cases showed that 32 cases (80%) were definitely exposed to asbestos; six cases (15%) were probably exposed and two (5%) had no known exposure. The mean latent interval was 34 years. Occupational histories of 56 control patients matched in pairs for age and sex with 28 of the mesothelioma cases revealed definite exposure to asbestos in 12 controls (21%), probable exposure in 11 (20%), and no evidence of exposure in 33 (59%). The difference in incidence of exposure between mesotheliomas and controls is statistically highly significant. Six-micron histological sections of lung, available in 39 mesothelioma cases, contained coated asbestos fibres in 36 cases (92%). Sixteen cases of mesothelioma showing fibres were free of asbestosis; asbestosis was slight in 14 cases, moderately severe in five cases, and severe in one case. The incidence of asbestos bodies in sections from mesothelioma cases was significantly higher than in a previously reported series of routine necropsies examined by lung smear.
Counts of coated and uncoated asbestos fibres were performed on samples of lung tissue from 33 mesothelioma cases. No fibres were identified in one case and only occasional coated fibres in a second case. The remainder gave counts ranging from 154 thousand to 684 million fibres per gram dry weight. Uncoated fibres were invariably present and usually comprised 50 to 80% of the count. No relationship was found between total fibre count and the latent period of the mesothelioma. Fibre counts were also performed on lung samples from 18 smear-positive and 30 smear-negative routine necropsies. Cases with numerous coated fibres in the smear gave total fibre counts similar to those of mesothelioma cases without asbestosis. Routine cases with only one fibre in the smear usually yielded only occasional fibres on analysis. Coated and uncoated fibres were found in 13 out of 30 smear-negative cases, indicating a true incidence of 56% of exposure to asbestos in the whole necropsy series. When compared with the mesothelioma series the difference in incidence of fibres remains statistically significant.
The data suggest that, on Tyneside, exposure to asbestos sufficient to cause an appreciable risk of developing mesothelioma has usually occurred through occupational exposure rather than by general environmental pollution by asbestos.
PMCID: PMC477900  PMID: 4766195
17.  Reliability of Routinely Collected Hospital Data for Child Maltreatment Surveillance 
BMC Public Health  2011;11:8.
Internationally, research on child maltreatment-related injuries has been hampered by a lack of available routinely collected health data to identify cases, examine causes, identify risk factors and explore health outcomes. Routinely collected hospital separation data coded using the International Classification of Diseases and Related Health Problems (ICD) system provide an internationally standardised data source for classifying and aggregating diseases, injuries, causes of injuries and related health conditions for statistical purposes. However, there has been limited research to examine the reliability of these data for child maltreatment surveillance purposes. This study examined the reliability of coding of child maltreatment in Queensland, Australia.
A retrospective medical record review and recoding methodology was used to assess the reliability of coding of child maltreatment. A stratified sample of hospitals across Queensland was selected for this study, and a stratified random sample of cases was selected from within those hospitals.
In 3.6% of cases the coders disagreed on whether any maltreatment code could be assigned (definite or possible) versus no maltreatment being assigned (unintentional injury), giving a sensitivity of 0.982 and specificity of 0.948. The review of these cases where discrepancies existed revealed that all cases had some indications of risk documented in the records. 15.5% of cases originally assigned a definite or possible maltreatment code, were recoded to a more or less definite strata. In terms of the number and type of maltreatment codes assigned, the auditor assigned a greater number of maltreatment types based on the medical documentation than the original coder assigned (22% of the auditor coded cases had more than one maltreatment type assigned compared to only 6% of the original coded data). The maltreatment types which were the most 'under-coded' by the original coder were psychological abuse and neglect. Cases coded with a sexual abuse code showed the highest level of reliability.
Given the increasing international attention being given to improving the uniformity of reporting of child-maltreatment related injuries and the emphasis on the better utilisation of routinely collected health data, this study provides an estimate of the reliability of maltreatment-specific ICD-10-AM codes assigned in an inpatient setting.
PMCID: PMC3022700  PMID: 21208411
18.  Active or Passive Exposure to Tobacco Smoking and Allergic Rhinitis, Allergic Dermatitis, and Food Allergy in Adults and Children: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001611.
In a systematic review and meta-analysis, Bahi Takkouche and colleagues examine the associations between exposure to tobacco smoke and allergic disorders in children and adults.
Please see later in the article for the Editors' Summary
Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases, especially among children, and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. The objective of this study was to examine the evidence for an association between active smoking (AS) or passive exposure to secondhand smoke and allergic conditions.
Methods and Findings
We retrieved studies published in any language up to June 30th, 2013 by systematically searching Medline, Embase, the five regional bibliographic databases of the World Health Organization, and ISI-Proceedings databases, by manually examining the references of the original articles and reviews retrieved, and by establishing personal contact with clinical researchers. We included cohort, case-control, and cross-sectional studies reporting odds ratio (OR) or relative risk (RR) estimates and confidence intervals of smoking and allergic conditions, first among the general population and then among children.
We retrieved 97 studies on allergic rhinitis, 91 on allergic dermatitis, and eight on food allergy published in 139 different articles. When all studies were analyzed together (showing random effects model results and pooled ORs expressed as RR), allergic rhinitis was not associated with active smoking (pooled RR, 1.02 [95% CI 0.92–1.15]), but was associated with passive smoking (pooled RR 1.10 [95% CI 1.06–1.15]). Allergic dermatitis was associated with both active (pooled RR, 1.21 [95% CI 1.14–1.29]) and passive smoking (pooled RR, 1.07 [95% CI 1.03–1.12]). In children and adolescent, allergic rhinitis was associated with active (pooled RR, 1.40 (95% CI 1.24–1.59) and passive smoking (pooled RR, 1.09 [95% CI 1.04–1.14]). Allergic dermatitis was associated with active (pooled RR, 1.36 [95% CI 1.17–1.46]) and passive smoking (pooled RR, 1.06 [95% CI 1.01–1.11]). Food allergy was associated with SHS (1.43 [1.12–1.83]) when cohort studies only were examined, but not when all studies were combined.
The findings are limited by the potential for confounding and bias given that most of the individual studies used a cross-sectional design. Furthermore, the studies showed a high degree of heterogeneity and the exposure and outcome measures were assessed by self-report, which may increase the potential for misclassification.
We observed very modest associations between smoking and some allergic diseases among adults. Among children and adolescents, both active and passive exposure to SHS were associated with a modest increased risk for allergic diseases, and passive smoking was associated with an increased risk for food allergy. Additional studies with detailed measurement of exposure and better case definition are needed to further explore the role of smoking in allergic diseases.
Please see later in the article for the Editors' Summary
Editors' Summary
The immune system protects the human body from viruses, bacteria, and other pathogens. Whenever a pathogen enters the body, immune system cells called T lymphocytes recognize specific molecules on its surface and release chemical messengers that recruit and activate other types of immune cells, which then attack the pathogen. Sometimes, however, the immune system responds to harmless materials (for example, pollen; scientists call these materials allergens) and triggers an allergic disease such as allergic rhinitis (inflammation of the inside of the nose; hay fever is a type of allergic rhinitis), allergic dermatitis (also known as eczema, a disease characterized by dry, itchy patches on the skin), and food allergy. Recent studies suggest that all these allergic (atopic) diseases are part of a continuous state called the “atopic march” in which individuals develop allergic diseases in a specific sequence that starts with allergic dermatitis during infancy, and progresses to food allergy, allergic rhinitis, and finally asthma (inflammation of the airways).
Why Was This Study Done?
Allergic diseases are extremely common, particularly in children. Allergic rhinitis alone affects 10%–30% of the world's population and up to 40% of children in some countries. Moreover, allergic diseases are becoming increasingly common. Allergic diseases affect the quality of life of patients and are financially costly to both patients and health systems. It is important, therefore, to identify the factors that cause or potentiate their development. One potential risk factor for allergic diseases is active or passive exposure to tobacco smoke. In some countries up to 80% of children are exposed to second-hand smoke so, from a public health point of view, it would be useful to know whether exposure to tobacco smoke is associated with the development of allergic diseases. Here, the researchers undertake a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical approach for combining the results of several studies) to investigate this issue.
What Did the Researchers Do and Find?
The researchers identified 196 observational studies (investigations that observe outcomes in populations without trying to affect these outcomes in any way) that examined the association between smoke exposure and allergic rhinitis, allergic dermatitis, or food allergy. When all studies were analyzed together, allergic rhinitis was not associated with active smoking but was slightly associated with exposure to second-hand smoke. Specifically, compared to people not exposed to second-hand smoke, the pooled relative risk (RR) of allergic rhinitis among people exposed to second-hand smoke was 1.10 (an RR of greater than 1 indicates an increased risk of disease development in an exposed population compared to an unexposed population). Allergic dermatitis was associated with both active smoking (RR = 1.21) and exposure to second-hand smoke (RR = 1.07). In the populations of children and adolescents included in the studies, allergic rhinitis was associated with both active smoking and exposure to second-hand smoke (RRs of 1.40 and 1.09, respectively), as was allergic dermatitis (RRs of 1.36 and 1.06, respectively). Finally food allergy was associated with exposure to second-hand smoke (RR = 1.43) when cohort studies (a specific type of observational study) only were examined but not when all the studies were combined.
What Do These Findings Mean?
These findings provide limited evidence for a weak association between smoke exposure and allergic disease in adults but suggest that both active and passive smoking are associated with a modestly increased risk of allergic diseases in children and adolescents. The accuracy of these findings may be affected by the use of questionnaires to assess smoke exposure and allergic disease development in most of the studies in the meta-analysis and by the possibility that individuals exposed to smoke may have shared other characteristics that were actually responsible for their increased risk of allergic diseases. To shed more light on the role of smoking in allergic diseases, additional studies are needed that accurately measure exposure and outcomes. However, the present findings suggest that, in countries where many people smoke, 14% and 13% of allergic rhinitis and allergic dermatitis, respectively, among children may be attributable to active smoking. Thus, the elimination of active smoking among children and adolescents could prevent one in seven cases of allergic rhinitis and one in eight cases of allergic dermatitis in such countries.
Additional Information
Please access these websites via the online version of this summary at
The UK National Health Service Choices website provides information about allergic rhinitis, hay fever (including personal stories), allergic dermatitis (including personal stories), and food allergy (including personal stories)
The US National Institute of Allergy and Infectious Disease provides information about allergic diseases
The UK not-for-profit organization Allergy UK provides information about all aspects of allergic diseases and a description of the atopic march
MedlinePlus encyclopedia has pages on allergic rhinitis and allergic dermatitis (in English and Spanish)
MedlinePlus provides links to further resources about allergies, eczema, and food allergy (in English and Spanish)
PMCID: PMC3949681  PMID: 24618794
19.  Community-Acquired Methicillin-Resistant Staphylococcus aureus: Prevalence and Risk Factors  
Journal of Athletic Training  2006;41(3):337-340.
Reference/Citation: Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis.20033613113912522744.
Clinical Question: What are the prevalence rates and risk factors associated with community-acquired methicillin-resistant Staphylococcus aureus (MRSA)?
Data Sources: Studies were identified by searching MEDLINE (January 1966–February 2002) and abstracts from scientific meetings (1996–2001). Reviews of citations and reference lists were performed to identify additional eligible studies. The search terms included Staphylococcus aureus , infection, colonization, methicillin resistance, community-acquired, community-onset, prevalence, frequency, and risk factors.
Study Selection: The search was limited to English-language investigations identified from the electronic and manual searches. Studies were divided into 2 groups, as follows: group 1, retrospective or prospective studies that reported the prevalence of community-acquired MRSA (CA-MRSA) among hospital patients who were colonized (presence of bacteria without infection) or infected with MRSA; and group 2, studies that reported the prevalence of MRSA colonization in the community. The studies were evaluated independently by 2 authors, and case reports were excluded.
Data Extraction: Data extraction and study quality assessment procedures were not fully explained. The outcome measures for hospital patients were definitions of CA-MRSA used in the study, prevalence of CA-MRSA, sample size, number and type of risk factors assessed, and number of patients with ≥1 health care–associated risk factor. The studies were grouped based on type, retrospective or prospective. The pooled prevalence of CA-MRSA was calculated for each group (retrospective or prospective) and was limited to the prevalence among patients with MRSA. The proportion of patients who reported ≥1 health care–associated risk factor was also calculated. The outcome measures among community members were prevalence of MRSA, sample size, number and type of risk factors assessed, number of members with ≥1 risk factor, and MRSA strain type, when available. The studies were grouped based on the population surveyed (surveillance cultures, contacts with MRSA-colonized individuals, or sport team members or day care contacts). The pooled prevalence of MRSA colonization and the proportion of members with ≥1 reported risk factor were calculated for each of the study populations listed above. The proportion of CA-MRSA strains that represented typical nosocomial (infection that develops in the hospital) strains was also determined. Chi-square analysis was performed to compare proportions and to determine heterogeneity among the studies.
Main Results: Specific search criteria identified 104 studies for review, of which 57 met inclusion and exclusion criteria. Thirty-nine studies focused on CA-MRSA among hospital patients who were colonized or infected with MRSA. Of these, 32 groups (27 retrospective, 5 prospective) reported the prevalence of CA-MRSA using clinical specimens. Seven groups identified risk factors of CA-MRSA among patients previously diagnosed with MRSA. Thirteen different definitions of CA-MRSA were used in 31 of these studies, and 8 groups did not report the definitions used. The isolation of MRSA within 48 hours of hospital admission, with or without recent admission to a hospital or long-term care facility, or previous history of MRSA colonization were the most common definitions in the studies.
The risk factors included recent hospitalization (range, 1–24 months before identification of MRSA infection or colonization), recent outpatient visit (usually within 12 months), recent nursing home admission (usually within 12 months), recent antibiotic exposure (range, 1–12 months), chronic illness (eg, end-stage renal disease, diabetes, or malignancy), injection drug use, and close contact with a person who had risk factor(s) for MRSA acquisition. The presence of health care–associated risk factors was examined in 17 of the retrospective studies, and the median number of factors studied was 2 (range, 1–6). Among 4121 patients in these studies, 86.1% were found to have ≥1 health care–associated risk factor. All authors of prospective studies (5) examined health care–associated risk factors, and the median number of factors studied was 4 (range, 2–4). Among the 636 patients, 86.9% had ≥1 health care–associated risk factor. In the 7 studies with 515 patients previously diagnosed with MRSA, 84.7% had ≥1 health care–associated risk factor. The most common risk factors assessed in the 17 retrospective studies were recent hospitalization and chronic illness requiring health care visits.
The pooled CA-MRSA prevalence was 30.2% (range, 1.9%– 96%) among 5932 patients from the 27 retrospective studies and 37.3% (range, 18.2%–51.2%) among 636 patients from the 5 prospective studies. Eighteen groups reported the prevalence of MRSA colonization in the community. Ten of these reported MRSA prevalence using surveillance cultures, 4 examined colonization status of household contacts with discharged hospital patients with nosocomial MRSA colonization, and 4 reported colonization status of sports team members or day care contacts of persons colonized with MRSA. In the 10 surveillance studies, the pooled MRSA colonization prevalence was 1.3% (95% confidence interval [CI], 1.04%–1.53%; range, 0.2%– 7.4%) among 8350 community members. Nine of these studies were stratified based on culture samples taken before the assessment of risk factors, and among 4825 people, the pooled MRSA colonization prevalence was 2.1%. When examining health care–associated risk factors, the median number of factors studied was 5 (range, 1–10), and 47.5% with MRSA had ≥1 health care–associated risk factor. The risk factors included those previously identified. In the remaining surveillance study, the MRSA colonization prevalence was 0.20% among 3525 people without prior health care contact. Compared with subjects in the 9 stratified studies with a health care contact, subjects in this study were 90% less likely to have MRSA (relative risk, 0.10; 95% CI, 0.05–0.21). Cultures for 3898 subjects in 7 of the 10 surveillance studies were obtained at the time of a hospital admission, an outpatient clinic visit, or an emergency department visit, and the pooled prevalence of MRSA colonization was 1.8%. In 3 studies in which cultures were obtained outside of a health care facility (schools, day care centers, homeless shelters, or military bases), the pooled MRSA colonization prevalence among 4452 subjects was reported to be 0.76%. Therefore, subjects in a health care facility were 2.35 times more likely to carry MRSA than were subjects outside of a health care facility (95% CI, 1.56–3.53). In one study examining 94 subjects in a semiclosed community, the prevalence of MRSA colonization was 7.4%. These subjects were 36 times more likely to carry MRSA than were subjects who were not in a semiclosed community (95% CI, 13.7–94.7).
The studies also identified 70 MRSA isolates (pure form of an organism in a microbial culture) from subjects who reported no health care–associated risk factors. Strain typing was performed with 32 isolates, and 29 (91%) isolates were similar to strains identified in hospitals. The colonization status of 191 household contacts of 93 patients with nosocomial MRSA colonization discharged from the hospital was examined in 4 studies. The results demonstrated that 17.8% of the contact subjects were colonized with a strain of MRSA having the same antibiogram (record of the susceptibility of bacteria to antibiotics) as the index case (initial individual with the strain). The authors reported that subjects who had household contacts with MRSA-colonized patients were 14 times more likely to be colonized than were community subjects without a known MRSA contact (95% CI, 9.8–20.1). In 4 studies examining 517 sports team members or day care contacts of persons known to be colonized with MRSA, 5.4% demonstrated colonization of MRSA with the same strain as the index case.
Conclusions: Based on the available data, the prevalence of MRSA among community members without health care–associated risk factors was relatively low. However, 85% of hospital patients diagnosed with CA-MRSA and 47.5% of healthy community members colonized with MRSA were found to have ≥1 health care–associated risk factor. The risk factors identified were recent hospitalization, outpatient visit, nursing home admission, antibiotic exposure, chronic illness, injection drug use, and close contact with a person with risk factor(s). Most MRSA colonization occurred among community members who had health care–associated risk factors or contact with persons with risk factors. The evidence indicated that control of MRSA in the community may require control of MRSA in the health care setting (hospital, health care office, and nursing home). The absence of a standardized definition for CA-MRSA and questions regarding the actual site of colonization versus acquisition should be considered in the interpretation of these findings.
PMCID: PMC1569547  PMID: 17043704
infectious diseases
20.  A case-control study of occupational magnetic field exposure and Alzheimer's disease: results from the California Alzheimer's Disease Diagnosis and Treatment Centers 
BMC Neurology  2007;7:13.
A few studies have investigated a possible relationship between Alzheimer's disease (AD) and occupations with extremely low frequency magnetic field (MF) exposure. The purpose of this study was to further evaluate this possible association in a large patient population with expert diagnoses.
Subjects came from the 8 of the 9 California Alzheimer's Disease Diagnostic and Treatment Centers not previously used in an earlier study. Cases had probable or definite AD; controls primarily had a dementia-related problem other than vascular dementia (VaD) and some were not demented upon expert examination. Occupations were classified as having low, medium or high MF exposure, based upon previous research, replicating the exposure methodology used in our previous published studies.
Occupational information was available for 98.6% of the 1527 cases and 98.5% of the 404 controls with age-at-initial examination known to be at least 65. Among cases, 2.1% and 5.4% had high and medium occupational MF exposure, respectively, while among controls the percentages were 0.8% and 3.0%. In univariate analyses, the odds ratio (OR) for subjects with medium or high MF exposures combined was 2.1 (p < 0.01), while for high exposure alone the OR was 2.9 (p < 0.08). Two models were used in multivariate analyses, with gender, stroke, and either age-at-onset or age-at-initial examination as covariates. The ORs for MF exposure varied little between the two models: 2.2 (p < 0.02) and 1.9 (p < 0.03) for medium or high exposure; 2.7 (p < 0.11) and 3.2 (p < 0.12) for high exposure. OR estimates for females were higher than for males, but not significantly higher. There were no material differences between the ORs resulting from univariate and multivariate analyses.
Elevated occupational MF exposure was associated with an increased risk of AD. Based on previous published studies, the results likely pertain to the general population.
PMCID: PMC1906833  PMID: 17559686
21.  Socio-economic class, rurality and risk of cutaneous melanoma by site and gender in Sweden 
BMC Public Health  2008;8:33.
Cutaneous melanoma (CM) is a cancer usually associated with high socio-economic level in the literature. Few studies have, however, assessed this relationship by gender and site or the association between CM and rurality.
A major-sized historical occupational Swedish cohort comprising 2,992,166 workers was used to estimate relative risk of cutaneous melanoma, broken down by gender and anatomical site, for occupational sectors (as a proxy of socio-economic class) and rurality. To this end, Poisson models were fitted for each site in men and women, including occupational sector and town size, with adjustment for age, period of diagnosis and geographical area as possible confounding factors.
White collar workers presented a marked increased of risk in men in all melanoma cases, as well as in trunk, upper and lower limbs. This pattern was less clear for women, in which some heterogeneity appeared, as low risks in lower socioeconomic sectors in trunk, or risk excesses in white collar workers in lower limbs did not achieve statistical significance. Males also showed significant differences in risk by rural/urban distribution, but in women this association was limited to CM of lower limb. Risk of CM of head/neck did not vary by occupational sector or town size, thus depicting a specific epidemiological profile, which proved common to both sexes.
While differences in risk between men and women could suggest greater homogeneity in UV-exposure behaviour among women, the uniform risk pattern in head and neck melanoma, present in both sexes, might support the coexistence of different aetiological pathways, related to anatomical site.
PMCID: PMC2266924  PMID: 18221505
22.  Definition of biochemical recurrence after radical prostatectomy does not substantially impact estimates for prognostic factors 
The Journal of urology  2010;183(3):984-989.
Biochemical recurrence (BCR) is used as a surrogate endpoint following radical prostatectomy. A large number of different definitions of BCR are currently used in the research literature. We examine various definitions of BCR in a large clinical cohort to explore whether estimation differs by definition.
Materials and Methods
The cohort included 5473 patients who underwent radical prostatectomy from 1985 to 2007 at Memorial Sloan-Kettering Cancer Center. Separate analyses were performed using 12 definitions of BCR that have been used in published studies. Cox regression was used to estimate hazard ratios for established predictors. Predictive accuracy was determined using the concordance index.
Depending on the definition used, the recurrence-free probability ranged from 86% to 91% at 3 years and from 81% to 87% at 5 years. Hazard ratios tended to be smaller for the most inclusive definitions, but were fairly similar across all definitions. The univariate hazard ratio for log PSA ranged from 2.1 to 2.4; for clinical stage T2b vs ≤T2a from 2.4 to 2.5; and for biopsy Gleason grade ≥8 vs ≤6 from 9.8 to 15. Multivariable hazard ratios were more homogeneous across the definitions. The concordance index ranged from 0.80–0.83 for the preoperative nomogram and from 0.83–0.88 for the postoperative nomogram.
Estimates of risk ratios and predictive accuracy are generally robust to the definition of BCR. For clinical research, papers using different definitions will come to similar conclusions on prognostic factors. The definition should be factored into papers comparing overall recurrence probabilities.
PMCID: PMC2919806  PMID: 20083281
prostate; prostatic neoplasms; prostatectomy; prostate-specific antigen; biological markers; recurrence
23.  Melanoma and occupation: results of a case-control study. 
OBJECTIVES: Associations between occupational exposures and the occurrence of cutaneous melanoma were examined as part of a large population based case-control study of 19 cancer sites. METHODS: Cases were men aged 35 to 70 years old, resident in Montreal, Canada, with a new histologically confirmed cutaneous melanoma (n = 103). There were two control groups, a randomly selected population control group (n = 533), and a cancer control group (n = 533) randomly selected from among subjects with other types of cancer in the large study. Odds ratios for the occurrence of melanoma were calculated for each exposure circumstance for which there were more than four exposed cases (85 substances, 13 occupations, and 20 industries) adjusting for age, ethnicity, and number of years of schooling. RESULTS: Significantly increased risk of melanoma was found for exposure to four substances (fabric dust, plastic dust, trichloroethylene, and a group containing paints used on surfaces other than metal and varnishes used on surfaces other than wood), three occupations (warehouse clerks, salesmen, and miners and quarrymen), and two industries (clothing and non-metallic mineral products). CONCLUSIONS: Most of the occupational circumstances examined were not associated with melanoma, nor is there any strong evidence from previous research that any of those are risk factors. For the few occupational circumstances which were associated in our data with melanoma, the statistical evidence was weak, and there is little or no supporting evidence in the scientific literature. On the whole, there is no persuasive evidence of occupational risk factors for melanoma, but the studies have been too small or have involved too much misclassification of exposure for this conclusion to be definitive.
PMCID: PMC1128439  PMID: 8704857
24.  Familial, Environmental, and Occupational Risk Factors in Development of Amyotrophic Lateral Sclerosis 
Definite etiology of amyotrophic lateral sclerosis (ALS) is still a matter of debate.
The study was designed to evaluate the role of environmental, occupational, and familial risk factors in development of ALS.
Materials and Methods:
This was a case control study of 110 cases of definite ALS with 240 age and sex matched controls. Investigations were done on the following aspects- family history, occupation, living place, source of drinking water, exposure to industrial, chemical, agricultural toxins and heavy metals, physical and electrical injury, working under magnetic field for more than 10 years in both the groups. Clinical examinations, electrophysiological, and neuroimaging studies were done in every patient. Chi square test, logistic regression analysis, and calculation of odds ratio were used to analyze the data.
Rural livings (odds ratio = 1.99), smoking (odds ratio = 1.88), insecticides, and pesticides exposures (odds ratio = 1.61), electrical injury (odds ratio = 6.2) were detected as the associated factors in development amyotrophic lateral sclerosis.
The study expressed the need of extensive research globally in molecular and genetic levels to detect the associated factors in etiopathogenesis of ALS for better understanding the etiology and for remedial aspects.
PMCID: PMC3421913  PMID: 22912943
Amyotropic lateral sclerosis; Environmental; Familial; Occupational risk factors
25.  An Evidence-Based Unified Definition of Lifelong and Acquired Premature Ejaculation: Report of the Second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation 
Sexual Medicine  2014;2(2):41-59.
The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE.
The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE.
In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted.
The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy.
The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE. Serefoglu EC, McMahon CG, Waldinger MD, Althof SE, Shindel A, Adaikan G, Becher EF, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. Sex Med 2014;2:41–59.
PMCID: PMC4184676  PMID: 25356301
Premature Ejaculation; Definition; Lifelong Premature Ejaculation; Acquired Premature Ejaculation; Intravaginal Ejaculatory Latency Time; Ejaculatory Control; Sexual Satisfaction; Personal Distress; Interpersonal Distress; Negative Personal Psychological Consequences

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