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1.  Occupational Injuries in Germany: Population-Wide National Survey Data Emphasize the Importance of Work-Related Factors 
PLoS ONE  2016;11(2):e0148798.
Unintentional injuries cause much of the global mortality burden, with the workplace being a common accident setting. Even in high-income economies, occupational injury figures remain remarkably high. Because risk factors for occupational injuries are prone to confounding, the present research takes a comprehensive approach. To better understand the occurrence of occupational injuries, sociodemographic factors and work- and health-related factors are tested simultaneously. Thus, the present analysis aims to develop a comprehensive epidemiological model that facilitates the explanation of varying injury rates in the workplace. The representative phone survey German Health Update 2010 provides information on medically treated occupational injuries sustained in the year prior to the interview. Data were collected on sociodemographics, occupation, working conditions, health-related behaviors, and chronic diseases. For the economically active population (18–70 years, n = 14,041), the 12-month prevalence of occupational injuries was calculated with a 95% confidence interval (CI). Blockwise multiple logistic regression was applied to successively include different groups of variables. Overall, 2.8% (95% CI 2.4–3.2) of the gainfully employed population report at least one occupational injury (women: 0.9%; 95% CI 0.7–1.2; men: 4.3%; 95% CI 3.7–5.0). In the fully adjusted model, male gender (OR 3.16) and age 18–29 (OR 1.54), as well as agricultural (OR 5.40), technical (OR 3.41), skilled service (OR 4.24) or manual (OR 5.12), and unskilled service (OR 3.13) or manual (OR 4.97) occupations are associated with higher chances of occupational injuries. The same holds for frequent stressors such as heavy carrying (OR 1.78), working in awkward postures (OR 1.46), environmental stress (OR 1.48), and working under pressure (OR 1.41). Among health-related variables, physical inactivity (OR 1.47) and obesity (OR 1.73) present a significantly higher chance of occupational injuries. While the odds for most work-related factors were as expected, the associations for health-related factors such as smoking, drinking, and chronic diseases were rather weak. In part, this may be due to context-specific factors such as safety and workplace regulations in high-income countries like Germany. This assumption could guide further research, taking a multi-level approach to international comparisons.
PMCID: PMC4747528  PMID: 26859560
2.  A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project 
BMC Public Health  2011;11:195.
Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two.
About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained.
Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses.
Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed.
Using standardized questionnaires, occupational exposure will be determined in exposed nurses only, whereas potential confounders (medicine consumption, lifestyle habits, diet and other non-occupational exposures) will be assessed in both groups of hospital workers.
Statistical analysis will be performed to ascertain the association between occupational exposure to antineoplastic drugs and biomarkers of DNA and chromosome damage, after taking into account the effects of individual genetic susceptibility, and the presence of confounding exposures.
The findings of the study will be useful in updating prevention procedures for handling antineoplastic drugs.
PMCID: PMC3074546  PMID: 21450074
3.  Underwater and Hyperbaric Medicine as a Branch of Occupational and Environmental Medicine 
Exposure to the underwater environment for occupational or recreational purposes is increasing. As estimated, there are around 7 million divers active worldwide and 300,000 more divers in Korea. The underwater and hyperbaric environment presents a number of risks to the diver. Injuries from these hazards include barotrauma, decompression sickness, toxic effects of hyperbaric gases, drowning, hypothermia, and dangerous marine animals. For these reasons, primary care physicians should understand diving related injuries and assessment of fitness to dive. However, most Korean physicians are unfamiliar with underwater and hyperbaric medicine (UHM) in spite of scientific and practical values.
From occupational and environmental medicine (OEM) specialist’s perspective, we believe that UHM should be a branch of OEM because OEM is an area of medicine that deals with injuries caused by physical and biological hazards, clinical toxicology, occupational diseases, and assessment of fitness to work. To extend our knowledge about UHM, this article will review and update on UHM including barotrauma, decompression illness, toxicity of diving gases and fitness for diving.
PMCID: PMC3923352  PMID: 24472678
Underwater and hyperbaric medicine; Occupational and environmental medicine; Barotrauma; Decompression illness; Toxicity of diving gases; Fitness for diving
4.  Requirements for occupational medicine training in Europe: a Delphi study 
OBJECTIVES—To identify the common core competencies required for occupational physicians in Europe.
METHOD—A modified Delphi survey was conducted among members of the European Association of Schools of Occupational Medicine (EASOM), the Occupational Medicine Section of the Union of European Medical Specialities (UEMS), and of the European Network of Societies of Occupational Physicians (ENSOP). An initial questionnaire based on the training syllabus of the United Kingdom Faculty of Occupational Medicine was circulated and respondents were asked to rate the importance of each item. The results were discussed at a conference on the subject of competencies. A further questionnaire was developed and circulated which asked respondents to rank items within each section.
RESULTS—There was a 74% response in the first round and an 80% response in the second. Respondents' ratings from most important to least important were; occupational hazards to health, research methods, health promotion, occupational health law and ethics, communications, assessment of disability, environmental medicine, and management. In the second round, among those topics ranked most highly were; hazards to health and the illnesses which they cause, control of risks, and diagnoses of work related ill health. Topics such as principles of occupational safety and selection of personal protection equipment were of least importance. Although the assessment of fitness was regarded as important, monitoring and advising on sickness absence were not highly rated. Management competency was regarded as of low importance.
CONCLUSION—This survey identified that respondents had traditional disease focused views of the competencies required of occupational physicians and that competencies were lagging behind the evolving definition of occupational health.

Keywords: competencies; Delphi study; occupational medicine training
PMCID: PMC1739906  PMID: 10711277
5.  Occupational Stress and Physical Symptoms among Family Medicine Residents 
The purpose of this study was to examine the levels of occupational stress and physical symptoms among family medicine residents and investigate the effect of subscales of occupational stress on physical symptoms.
A self-administered questionnaire survey of 1,152 family medicine residents was carried out via e-mail from April 2010 to July 2010. The response rate was 13.1% and the R (ver. 2.9.1) was used for the analysis of completed data obtained from 150 subjects. The questionnaire included demographic factors, resident training related factors, 24-items of the Korean Occupational Stress Scales and Korean Versions of the Wahler Physical Symptom Inventory.
The total score of occupational stress of family medicine residents was relatively low compared to that of average workers. The scores of 'high job demand', 'inadequate social support', 'organizational injustice', and 'discomfort in occupational climate' were within the top 50%. Parameters associated with higher occupational stress included level of training, on-duty time, daily patient load, critical patient assigned, total working days, night duty day, sleep duration, and sleep quality. The six subscales of occupational stress, except for 'Job insecurity', had a significant positive correlation with physical symptom scores after adjustment had been made for potential confounders (total score, r = 0.325 and P < 0.001; high job demand, r = 0.439 and P < 0.001).
After the adjustment had been made for potential confounders, the total score of occupational stress and six subscales in family medicine residents showed a significant positive correlation with physical symptom scores.
PMCID: PMC3560340  PMID: 23372906
Stress; Signs and Symptoms; Family Physicians; Internship and Residency; Questionnaires
6.  Trend towards multiple authorship in occupational medicine journals 
There is an established trend towards an increasing number of authors per article in prestigious journals for medicine and health sciences. It is uncertain whether a similar trend occurs to the same extent in journals for specific medical specialties.
Journals focusing on occupational medicine were selected for analysis with regard to single or multiple-authorship per peer-reviewed paper. Data were collected from PubMed for publications between 1970 and 2007. These were analysed to calculate the average number of authors per multiple-author article per year and the percentage of single-author articles per year. The slope and average of these journals were then compared with that of previously studied non-occupational medicine journals.
The results confirm a trend towards a linear increase in the average number of authors per article and a linear decrease in the percentage of single-author articles. The slope for the average number of authors for multiple-author articles was significantly higher in the Journal of Occupational and Environmental Medicine than in the other occupational medicine journals. Computational analysis of all articles published showed that Occupational Medicine (Oxford) had a significantly higher percentage of single-author articles than the other occupational medicine journals as well as major journals previously studied.
The same trend towards multiple authorship can be observed in medical specialty journals as in major journals for medicine and health sciences. There is a direct relationship between occupational journals with higher impact factors and a higher average number of authors per article in those journals.
PMCID: PMC2645424  PMID: 19203357
7.  Fracture prevention in postmenopausal women 
BMJ Clinical Evidence  2011;2011:1109.
The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for the hip, with an exponential increase in risk beyond the age of 50 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of bisphosphonates to prevent fractures in postmenopausal women? What are the effects of pharmacological treatments other than bisphosphonates to prevent fractures in postmenopausal women? What are the effects of non-pharmacological treatments to prevent fractures in postmenopausal women? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: alendronate, calcium, calcium plus vitamin D, clodronate, denosumab, etidronate, exercise, hip protectors, hormone replacement therapy, ibandronate, multifactorial non-pharmacological interventions, pamidronate, parathyroid hormone, raloxifene, risedronate, strontium ranelate, vitamin D, vitamin D analogues, and zoledronate.dfsg
Key Points
The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for the hip, with an exponential increase in risk beyond the age of 50 years. About 13% of people die in the year after a hip fracture, and most survivors lose some or all of their previous independence.
Alendronate, risedronate, zoledronate, denosumab, and parathyroid hormone reduce vertebral and non-vertebral fractures compared with placebo. Etidronate, ibandronate, pamidronate, and raloxifene reduce vertebral fractures, but have not been shown to reduce non-vertebral fractures.Raloxifene protects against breast cancer, but increases venous thromboembolic events and stroke compared with placebo. Strontium ranelate reduces vertebral and, to some extent, non-vertebral fractures. Clodronate may reduce non-vertebral fractures at 3 years, but its effects on rate of vertebral fracture are unclear.
CAUTION: Hormone replacement therapy may reduce fractures, but it increases the risk of breast cancer and cardiovascular events. The risks of adverse effects of treatment are thought to outweigh the beneficial effects of hormone replacement therapy in prevention of fractures.
Combined calcium plus vitamin D or vitamin D analogues alone may reduce vertebral and non-vertebral fractures, but trials have given inconclusive results. Monotherapy with calcium or vitamin D has not been shown to reduce fractures, and calcium alone may potentially be associated with an increased risk of cardiovascular adverse effects.
We don't know whether multifactorial non-pharmacological interventions including environmental manipulation or regular exercise reduce the risk of fractures. Hip protectors may reduce the risk of hip fractures in nursing-home residents, but compliance tends to be low.
Calcitonin was included in an earlier version of this review. However, in light of a drug alert ( it was removed from this version because of new harms data. It will be covered in the next update of this review when these new harms data can be incorporated.
PMCID: PMC3217780  PMID: 21542947
8.  Public, environmental, and occupational health research activity in Arab countries: bibliometric, citation, and collaboration analysis 
The objective of this study was to analyze quantity, assess quality, and investigate international collaboration in research from Arab countries in the field of public, environmental and occupational health.
Original scientific articles and reviews published from the 22 Arab countries in the category "public, environmental & occupational health" during the study period (1900 – 2012) were screened using the ISI Web of Science database.
The total number of original and review research articles published in the category of "public, environmental & occupational health" from Arab countries was 4673. Main area of research was tropical medicine (1862; 39.85%). Egypt with 1200 documents (25.86%) ranked first in quantity and ranked first in quality of publications (h-index = 51). The study identified 2036 (43.57%) documents with international collaboration. Arab countries actively collaborated with authors in Western Europe (22.91%) and North America (21.04%). Most of the documents (79.9%) were published in public health related journals while 21% of the documents were published in journals pertaining to prevention medicine, environmental, occupational health and epidemiology.
Research in public, environmental and occupational health in Arab countries is in the rise. Public health research was dominant while environmental and occupation health research was relatively low. International collaboration was a good tool for increasing research quantity and quality.
PMCID: PMC4322552  PMID: 25671116
Arab countries; Public health; Environmental and occupational health; Bibliometric analysis; ISI web of science
9.  Design of the Balance@Work project: systematic development, evaluation and implementation of an occupational health guideline aimed at the prevention of weight gain among employees 
BMC Public Health  2009;9:461.
Occupational health professionals may play an important role in preventive health promotion activities for employees. However, due to a lack of knowledge and evidence- and practice based methods and strategies, interventions are hardly being implemented by occupational physicians to date. The aim of the Balance@Work project is to develop, evaluate, and implement an occupational health guideline aimed at the prevention of weight gain among employees.
Following the guideline development protocol of the Netherlands Society of Occupational Medicine and the Intervention Mapping protocol, the guideline was developed based on literature, interviews with relevant stakeholders, and consensus among an expert group. The guideline consists of an individual and an environmental component. The individual component includes recommendations for occupational physicians on how to promote physical activity and healthy dietary behavior based on principles of motivational interviewing. The environmental component contains an obesogenic environment assessment tool. The guideline is evaluated in a randomised controlled trial among 20 occupational physicians. Occupational physicians in the intervention group apply the guideline to eligible workers during 6 months. Occupational physicians in the control group provide care as usual. Measurements take place at baseline and 6, 12, and 18 months thereafter. Primary outcome measures include waist circumference, daily physical activity and dietary behavior. Secondary outcome measures include sedentary behavior, determinants of behavior change, body weight and body mass index, cardiovascular disease risk profile, and quality of life. Additionally, productivity, absenteeism, and cost-effectiveness are assessed.
Improving workers' daily physical activity and dietary behavior may prevent weight gain and subsequently improve workers' health, increase productivity, and reduce absenteeism. After an effect- and process evaluation the guideline will be adjusted and, after authorisation, published. Together with several implementation aids, the published guideline will be disseminated broadly by the Netherlands Society of Occupational Medicine.
Trial Registration
PMCID: PMC2799413  PMID: 20003405
10.  Environmental and Occupational Causes of Cancer New Evidence, 2005–2007 
Executive Summary
What do we currently know about the occupational and environmental causes of cancer? As of 2007, the International Agency for Research on Cancer has identified 415 known or suspected carcinogens. Cancer arises through an extremely complicated web of multiple causes. We will likely never know the full range of agents or combinations of agents that cause cancer. However, we do know that preventing exposure to individual carcinogens prevents the disease. Declines in cancer rates – such as the drop in male lung cancer cases from the reduction in tobacco smoking or the drop in bladder cancer among cohorts of dye workers from the elimination of exposure to specific aromatic amines – provides evidence that preventing cancer is possible when we act on what we know. Although the overall age-adjusted cancer incidence rates in the U.S. among both men and women have declined in the last decade, rates of several types of cancers are on the rise; some of these cancers are linked to environmental and occupational exposures.
This report chronicles the most recent epidemiological evidence linking occupational and environmental exposures with cancer. Peer-reviewed scientific studies published from January 2005-June 2007 were reviewed, supplementing our state-of-the-evidence report published in September 2005. Despite weaknesses in some individual studies, we consider the evidence linking the increased risk of several types of cancer with specific exposures somewhat strengthened by recent publications, among them: brain cancer from exposure to non-ionizing radiation, particularly radiofrequency fields emitted by mobile telephones;breast cancer from exposure to the pesticide dichloro-diphenyl-trichloroethane (DDT) prior to puberty;leukemia from exposure to 1,3-butadiene;lung cancer from exposure to air pollution;non-Hodgkin's lymphoma (NHL) from exposure to pesticides and solvents; andprostate cancer from exposure to pesticides, polyaromatic hydrocarbons (PAHs), and metal working fluids or mineral oils.
In addition to NHL and prostate cancer, early findings from the Agricultural Health Study suggest that several additional cancers may be linked to a variety of pesticides.
Our report also briefly describes the toxicological evidence related to the carcinogenic effect of specific chemicals and mechanisms that are difficult to study in humans, namely exposures to bis-phenol A and epigenetic, trans-generational effects. To underscore the multi-factorial, multi-stage nature of cancer, we also present a technical description of cancer causation summarizing current knowledge in molecular biology.
We argue for a new cancer prevention paradigm, one that is based on an understanding that cancer is ultimately caused by multiple interacting factors rather than a paradigm based on dubious attributable fractions. This new cancer prevention paradigm demands that we limit exposures to avoidable environmental and occupational carcinogens in combination with additional important risk factors such as diet and lifestyle.
The research literature related to environmental and occupational causes of cancer is constantly growing and future updates will be carried out in light of new biological understanding of the mechanisms and new methods for studying exposures in human populations. However, the current state of knowledge is sufficient to compel us to act on what we know. We repeat the call of ecologist Sandra Steingraber, “From the right to know and the duty to inquire flows the obligation to act.” 1
PMCID: PMC2791455  PMID: 18557596
11.  Environmental medicine in Germany--a review. 
Environmental Health Perspectives  2002;110(Suppl 1):113-118.
In this review I describe the development of environmental medicine as a specialized field of clinical medicine in Germany. New scientific societies were founded, based on traditions of public hygiene and occupational medicine, as a reaction to environmental issues concerning human health. Environmental medicine issues were also addressed by independent "critical" physicians. The first institutions to accept patients were centers for environmental medicine affiliated with research institutions and/or with the public health service. Medical professional organizations, particularly the German General Medical Council, described the need for and formulated conditions for additional qualification for doctors in environmental medicine, including a 200-hr course. This course and a qualifying exam were passed by about 3,000 doctors, mainly from the public health service and from occupational medicine. Unfortunately, few general physicians in primary outpatient care were similarly trained. To date, no representative study has been conducted on environmental patients, but I include in this review a typical list of patients' complaints. I also summarize research activities typical for environmental medicine in Germany. Present problems concern accounting systems and, for example, diagnosis and treatment of patients with multiple chemical sensitivities (MCS). A coordinated research program on MCS has been started.
PMCID: PMC1241153  PMID: 11834469
12.  Developing and analysing a curriculum map in Occupational- and Environmental Medicine 
BMC Medical Education  2010;10:60.
During the last 5 years a fundamental curriculum reform was realized at the medical school of the Ludwig-Maximilians-University. In contrast to those efforts, the learning objectives were not defined consistently for the curriculum and important questions concerning the curriculum could not be answered. This also applied to Occupational and Environmental Medicine where teachers of both courses were faced with additional problems such as the low number of students attending the lectures.
The aims of the study were to develop and analyse a curriculum map for Occupational and Environmental Medicine based on learning objectives using a web-based database.
Furthermore we aimed to evaluate student perception about the curricular structure.
Using a web-based learning objectives database, a curriculum map for Occupational and Environmental Medicine was developed and analysed. Additionally online evaluations of students for each course were conducted.
The results show a discrepancy between the taught and the assessed curriculum. For both curricula, we identified that several learning objectives were not covered in the curriculum. There were overlaps with other content domains and redundancies within both curricula. 53% of the students in Occupational Medicine and 43% in Environmental Medicine stated that there is a lack of information regarding the learning objectives of the curriculum.
The results of the curriculum mapping and the poor evaluation results for the courses suggest a need for re-structuring both curricula.
PMCID: PMC2944147  PMID: 20840737
13.  The purpose of occupational medicine. 
The purposes of occupational medicine are described in terms of its clinical medical, environmental medical, research, and administrative content. Each of these components is essential in different proportions in comprehensive occupational health services for different industries, and can only be satisfactorily provided by occupational physicians and occupational health nurses who are an integral part of their organizations. Two-thirds of the working population in the United Kingdom are without the benefits of occupational medicine. The reorganization of the National Health Service and of local government presents the opportunity to extend occupational health services to many more workers who need them. It is suggested that area health authorities should provide occupational health services for all National Health Service staff and, on an agency basis, for local government and associated services, eventually extending to local industry. Such area health authority based services, merged with the Employment Medical Advisory Service, could conveniently then be part of the National Health Service, as recommended by the British Medical Association, the Society of Occupational Medicine, and the Medical Services Review Committee.
PMCID: PMC1008034  PMID: 1131336
14.  Acupuncture for glaucoma 
Glaucoma is a multifactorial optic neuropathy in which there is an acquired loss of retinal ganglion cells at levels beyond normal age-related loss and corresponding atrophy of the optic nerve. Although there are many existing treatments, glaucoma is a chronic condition. Some patients may seek complementary or alternative medicine such as acupuncture to supplement their regular treatment. The underlying plausibility of acupuncture is that disorders related to the flow of Chi (the traditional Chinese concept translated as vital force or energy) can be prevented or treated by stimulating the relevant points on the body surface.
The objective of this review was to assess the effectiveness and safety of acupuncture in people with glaucoma.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 3), MEDLINE (January 1950 to March 2010), EMBASE (January 1980 to March 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2010), ZETOC (January 1993 to March 2010), Allied and Complementary Medicine Database (AMED) (January 1985 to March 2010), the metaRegister of Controlled Trials (mRCT) (, ( and the National Center for Complementary and Alternative Medicine web site (NCCAM) ( There were no language or date restrictions in the search for trials. The electronic databases were last searched on 23 March 2010 with the exception of NCCAM which was last searched on 14 July 2010. We also handsearched Chinese medical journals at Peking Union Medical College Library in April 2007.
Although the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Chinese Acupuncture Trials Register, the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and the Chinese Biological Database (CBM) were searched for the original review, we did not search these databases for the 2010 review update.
Selection criteria
We planned to include randomized and quasi-randomized clinical trials in which one arm of the study involved acupuncture treatment.
Data collection and analysis
Two authors independently evaluated the search results against the inclusion and exclusion criteria. Discrepancies were resolved by discussion.
Main results
We found no randomized clinical trials and subsequently no meta-analysis was conducted. Evidence was limited to a few case series of small sample size.
Authors’ conclusions
At this time, it is impossible to draw reliable conclusions from the available data to support the use of acupuncture for the treatment of glaucoma. Since most glaucoma patients currently cared for by ophthalmologists do not use non-traditional therapy, the clinical practice decisions will have to be based on physician judgement and patients’ value given this lack of data in the literature.
PMCID: PMC3804313  PMID: 17943876
15.  Bronchitis (acute) 
BMJ Clinical Evidence  2011;2011:1508.
Acute bronchitis affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens. The role of smoking or of environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear. One third of people may have longer-term symptoms or recurrence.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute bronchitis in people without chronic respiratory disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics, antibiotics (macrolides, tetracyclines, cephalosporins, penicillins, or trimethoprim–sulfamethoxazole [co-trimoxazole]), antihistamines, antitussives, beta2 agonists (inhaled or oral), and expectorants/mucolytics.
Key Points
Acute bronchitis affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens.The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.One third of people may have longer-term symptoms or recurrence.
Antibiotics lead to only a modest reduction in the duration of cough compared with placebo, and may increase the risks of adverse effects.
Concerns remain that widespread use of antimicrobials will lead to resistance. We don't know for sure whether any one antibiotic regimen is superior to the others.So far high-quality evidence to support the use of broad-spectrum antibiotics, such as quinolones or amoxicillin–clavulanic acid (co-amoxiclav), over amoxicillin alone in people with acute bronchitis is lacking.It has not been shown that smokers without lung disease are more likely to benefit from antibiotics than non-smokers.
We don't know whether analgesics, antihistamines, antitussives, inhaled or oral beta2 agonists, or expectorants and mucolytics improve symptoms of acute bronchitis compared with placebo, as we found few good-quality trials.
PMCID: PMC3275297  PMID: 21711957
16.  Occupational medicine and toxicology 
This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.
PMCID: PMC1436007
17.  The Magnitude of Mortality from Ischemic Heart Disease Attributed to Occupational Factors in Korea - Attributable Fraction Estimation Using Meta-analysis 
Safety and Health at Work  2011;2(1):70-82.
Ischemic heart disease (IHD) is a major cause of death in Korea and known to result from several occupational factors. This study attempted to estimate the current magnitude of IHD mortality due to occupational factors in Korea.
After selecting occupational risk factors by literature investigation, we calculated attributable fractions (AFs) from relative risks and exposure data for each factor. Relative risks were estimated using meta-analysis based on published research. Exposure data were collected from the 2006 Survey of Korean Working Conditions. Finally, we estimated 2006 occupation-related IHD mortality.
For the factors considered, we estimated the following relative risks: noise 1.06, environmental tobacco smoke 1.19 (men) and 1.22 (women), shift work 1.12, and low job control 1.15 (men) and 1.08 (women). Combined AFs of those factors in the IHD were estimated at 9.29% (0.3-18.51%) in men and 5.78% (-7.05-19.15%) in women. Based on these fractions, Korea's 2006 death toll from occupational IHD between the age of 15 and 69 was calculated at 353 in men (total 3,804) and 72 in women (total 1,246).
We estimated occupational IHD mortality of Korea with updated data and more relevant evidence. Despite the efforts to obtain reliable estimates, there were many assumptions and limitations that must be overcome. Future research based on more precise design and reliable evidence is required for more accurate estimates.
PMCID: PMC3431892  PMID: 22953190
Attributable fraction; Cardiovascular disease; Korea; Mortality; Occupation
18.  Update in Palliative Care - 2011 
The aim of this update is to summarize scientifically rigorous articles published in 2010 that serve to advance the field of palliative medicine and have an impact on clinical practice.
We conducted two separate literature searches for articles published between January 1, 2010 and December 31, 2010. We reviewed title pages from the Annals of Internal Medicine, British Medical Journal, Journal of the American Geriatrics Society, JAMA, Journal of Clinical Oncology, JGIM, Journal of Pain and Symptom Management, Journal of Palliative Medicine, Lancet, New England Journal of Medicine, PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care). We also conducted a Medline search with the key words "palliative," "hospice," and "terminal" care. Each author presented approximately 20 abstracts to the group. All authors reviewed these abstracts, and when needed, full text publications. We focused on articles relevant to general internists. We rated the articles individually, eliminating by consensus those that were not deemed of highest priority, and discussed the final choices as a group.
We first identified 126 articles with potential relevance. We presented 20 at the annual SGIM update session, and discuss 11 in this paper.
PMCID: PMC3326102  PMID: 22127796
palliative; end-of-life; communication; pain
19.  Required competencies of occupational physicians: a Delphi survey of UK customers 
Background: Occupational physicians can contribute to good management in healthy enterprises. The requirement to take into account the needs of the customers when planning occupational health services is well established.
Aims: To establish the priorities of UK employers, employees, and their representatives regarding the competencies they require from occupational physicians; to explore the reasons for variations of the priorities in different groups; and to make recommendations for occupational medicine training curricula in consideration of these findings.
Methods: This study involved a Delphi survey of employers and employees from public and private organisations of varying business sizes, and health and safety specialists as well as trade union representatives throughout the UK. It was conducted in two rounds by a combination of computer assisted telephone interview (CATI) and postal survey techniques, using a questionnaire based on the list of competencies described by UK and European medical training bodies.
Results: There was broad consensus about the required competencies of occupational physicians among the respondent subgroups. All the competencies in which occupational physicians are trained were considered important by the customers. In the order of decreasing importance, the competencies were: Law and Ethics, Occupational Hazards, Disability and Fitness for Work, Communication, Environmental Exposures, Research Methods, Health Promotion, and Management.
Conclusion: The priorities of customers differed from previously published occupational physicians' priorities. Existing training programmes for occupational physicians should be regularly reviewed and where necessary, modified to ensure that the emphasis of training meets customer requirements.
PMCID: PMC1741022  PMID: 15901889
20.  Reporting of occupational and environmental research: use and misuse of statistical and epidemiological methods 
OBJECTIVES—To report some of the most serious omissions and errors which may occur in papers submitted to Occupational and Environmental Medicine, and to give guidelines on the essential components that should be included in papers reporting results from studies of occupational and environmental health.
METHODS—Since 1994 Occupational and Environmental Medicine has used a panel of medical statisticians to review submitted papers which have a substantial statistical content. Although some studies may have genuine errors in their design, execution, and analysis, many of the problems identified during the reviewing process are due to inadequate and incomplete reporting of essential aspects of a study. This paper outlines some of the most important errors and omissions that may occur. Observational studies are often the preferred choice of design in occupational and environmental medicine. Some of the issues relating to design, execution, and analysis which should be considered when reporting three of the most common observational study designs, cross sectional, case-control, and cohort are described. An illustration of good reporting practice is given for each. Various mathematical modelling techniques are often used in the analysis of these studies, the reporting of which causes a major problem to some authors. Suggestions for the presentation of results from modelling are made.
CONCLUSIONS—There is increasing interest in the development and application of formal "good epidemiology practices". These not only consider issues of data quality, study design, and study conduct, but through their structured approach to the documentation of the study procedures, provide the potential for more rigorous reporting of the results in the scientific literature.

Keywords: research reporting; statistical methods; epidemiological methods
PMCID: PMC1739857  PMID: 10711263
21.  Geographical Inequalities in Use of Improved Drinking Water Supply and Sanitation across Sub-Saharan Africa: Mapping and Spatial Analysis of Cross-sectional Survey Data 
PLoS Medicine  2014;11(4):e1001626.
Using cross-sectional survey data, Rachel Pullan and colleagues map geographical inequalities in use of improved drinking water supply and sanitation across sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Understanding geographic inequalities in coverage of drinking-water supply and sanitation (WSS) will help track progress towards universal coverage of water and sanitation by identifying marginalized populations, thus helping to control a large number of infectious diseases. This paper uses household survey data to develop comprehensive maps of WSS coverage at high spatial resolution for sub-Saharan Africa (SSA). Analysis is extended to investigate geographic heterogeneity and relative geographic inequality within countries.
Methods and Findings
Cluster-level data on household reported use of improved drinking-water supply, sanitation, and open defecation were abstracted from 138 national surveys undertaken from 1991–2012 in 41 countries. Spatially explicit logistic regression models were developed and fitted within a Bayesian framework, and used to predict coverage at the second administrative level (admin2, e.g., district) across SSA for 2012. Results reveal substantial geographical inequalities in predicted use of water and sanitation that exceed urban-rural disparities. The average range in coverage seen between admin2 within countries was 55% for improved drinking water, 54% for use of improved sanitation, and 59% for dependence upon open defecation. There was also some evidence that countries with higher levels of inequality relative to coverage in use of an improved drinking-water source also experienced higher levels of inequality in use of improved sanitation (rural populations r = 0.47, p = 0.002; urban populations r = 0.39, p = 0.01). Results are limited by the quantity of WSS data available, which varies considerably by country, and by the reliability and utility of available indicators.
This study identifies important geographic inequalities in use of WSS previously hidden within national statistics, confirming the necessity for targeted policies and metrics that reach the most marginalized populations. The presented maps and analysis approach can provide a mechanism for monitoring future reductions in inequality within countries, reflecting priorities of the post-2015 development agenda.
Please see later in the article for the Editors' Summary
Editors' Summary
Access to a safe drinking-water supply (a water source that is protected from contamination) and to adequate sanitation facilities (toilets, improved latrines, and other facilities that prevent people coming into contact with human urine and feces) is essential for good health. Unimproved drinking-water sources and sanitation are responsible for 85% of deaths from diarrhea and 1% of the global burden of disease. They also increase the transmission of parasitic worms and other neglected tropical diseases. In 2000, world leaders set a target of reducing the proportion of the global population without access to safe drinking water and basic sanitation to half of the 1990 level by 2015 as part of Millennium Development Goal (MDG) 7 (“Ensure environmental sustainability”; the MDGs are designed to improve the social, economic, and health conditions in the world's poorest countries). Between 1990 and 2010, more than 2 billion people gained access to improved drinking-water sources and 1.8 billion gained access to improved sanitation. In 2011, 89% of the world's population had access to an improved drinking-water supply, 1% above the MDG target, and 64% had access to improved sanitation (the MDG target is 75%).
Why Was This Study Done?
Despite these encouraging figures, the WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation (JMP) estimates that, globally, 768 million people relied on unimproved drinking-water sources, 2.5 billion people did not use an improved sanitation facility, and more than 1 billion people (15% of the global population) were defecating in the open in 2011. The JMP estimates for 2011 also reveal national and sub-national inequalities in drinking-water supply and sanitation coverage but a better understanding of geographic inequalities is needed to track progress towards universal coverage of access to improved water and sanitation and to identify the populations that need the most help to achieve this goal. Here, the researchers use cross-sectional household survey data and modern statistical approaches to produce a comprehensive map of the coverage of improved drinking-water supply and improved sanitation at high spatial resolution for sub-Saharan Africa and to investigate geographic inequalities in coverage. Cross-sectional household surveys collect health and other information from households at a single time-point, including data on use of safe water and improved sanitation.
What Did the Researchers Do and Find?
The researchers extracted data on reported household use of an improved drinking-water supply (for example, a piped water supply), improved sanitation facilities (for example, a flushing toilet), and open defecation from 138 national household surveys undertaken between 1991 and 2012 in 41 countries in sub-Saharan Africa. They developed statistical models to fit these data and used the models to estimate coverage at the district (second administrative) level across sub-Saharan Africa for 2012. For ten countries, the estimated coverage of access to improved drinking water at the district level within individual countries ranged from less than 25% to more than 75%. Within-country ranges of a similar magnitude were estimated for coverage of access to improved sanitation (21 countries) and for open defecation (16 countries). Notably, rural households in the districts with the lowest coverage of access to improved water supply and sanitation within a country were 1.5–8 times less likely to access improved drinking water, 2–18 times less likely to access improved sanitation, and 2–80 times more likely to defecate in the open than rural households in districts with the best coverage. Finally, countries with high levels of inequality in improved drinking-water source coverage also experienced high levels of inequality in improved sanitation coverage.
What Do These Findings Mean?
These findings identify important geographic inequalities in the coverage of access to improved water sources and sanitation that were previously hidden within national statistics. The accuracy of these findings depends on the accuracy of the data on water supplies and sanitation provided by household surveys, on the researchers' definitions for improved water supplies and sanitation, and on their statistical methods. Nevertheless, these findings confirm that, to achieve universal coverage of access to improved drinking-water sources and sanitation, strategies that target the areas with the lowest coverage are essential. Moreover, the maps and the analytical approach presented here provide the means for monitoring future reductions in inequalities in the coverage of access to improved water sources and sanitation and thus reflect a major priority of the post-2015 development agenda.
Additional Information
Please access these websites via the online version of this summary at
A PLOS Medicine Collection on water and sanitation is available
The World Health Organization (WHO) provides information on water, sanitation, and health (in several languages)
The WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation is the official United Nations mechanism tasked with monitoring progress toward MDG7, Target 7B; the JMP 2013 update report is available online (also available in French and Spanish through the JMP website)
The sub-national predictions resulting from this study and the final sub-national maps are available as a resource for researchers and planners
PMCID: PMC3979660  PMID: 24714528
22.  Schizophrenia 
BMJ Clinical Evidence  2012;2012:1007.
The lifetime prevalence of schizophrenia is approximately 0.7% and incidence rates vary between 7.7 and 43.0 per 100,000; about 75% of people have relapses and continued disability, and one third fail to respond to standard treatment. Positive symptoms include auditory hallucinations, delusions, and thought disorder. Negative symptoms (demotivation, self-neglect, and reduced emotion) have not been consistently improved by any treatment.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? What are the effects of drug treatments in people with schizophrenia who are resistant to standard antipsychotic drugs? What are the effects of interventions to improve adherence to antipsychotic medication in people with schizophrenia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 51 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amisulpride, chlorpromazine, clozapine, depot haloperidol decanoate, haloperidol, olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine, aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol decanoate, zuclopenthixol, depot zuclopenthixol decanoate, behavioural therapy, clozapine, compliance therapy, first-generation antipsychotic drugs in treatment-resistant people, multiple-session family interventions, psychoeducational interventions, and second-generation antipsychotic drugs in treatment-resistant people.
Key Points
The lifetime prevalence of schizophrenia is approximately 0.7% and incidence rates vary between 7.7 and 43.0 per 100,000; about 75% of people have relapses and continued disability, and one third fail to respond to standard treatment. Positive symptoms include auditory hallucinations, delusions, and thought disorder. Negative symptoms (anhedonia, asociality, flattening of affect, and demotivation) and cognitive dysfunction have not been consistently improved by any treatment.
Standard treatment of schizophrenia has been antipsychotic drugs, the first of which included chlorpromazine and haloperidol, but these so-called first-generation antipsychotics can all cause adverse effects such as extrapyramidal adverse effects, hyperprolactinaemia, and sedation. Attempts to address these adverse effects led to the development of second-generation antipsychotics.
The second-generation antipsychotics amisulpride, clozapine, olanzapine, and risperidone may be more effective at reducing positive symptoms compared with first-generation antipsychotic drugs, but may cause similar adverse effects, plus additional metabolic effects such as weight gain.
CAUTION: Clozapine has been associated with potentially fatal blood dyscrasias. Blood monitoring is essential, and it is recommended that its use be limited to people with treatment-resistant schizophrenia.
Pimozide, quetiapine, aripiprazole, sulpiride, ziprasidone, and zotepine seem to be as effective as standard antipsychotic drugs at improving positive symptoms. Again, these drugs cause similar adverse effects to first-generation antipsychotics and other second-generation antipsychotics.
CAUTION: Pimozide has been associated with sudden cardiac death at doses above 20 mg daily.
We found very little evidence regarding depot injections of haloperidol decanoate, flupentixol decanoate, or zuclopenthixol decanoate; thus, we don’t know if they are more effective than oral treatments at improving symptoms.
In people who are resistant to standard antipsychotic drugs, clozapine may improve symptoms compared with first-generation antipsychotic agents, but this benefit must be balanced against the likelihood of adverse effects. We found limited evidence on other individual first- or second-generation antipsychotic drugs other than clozapine in people with treatment-resistant schizophrenia.In people with treatment-resistant schizophrenia, we don't know how second-generation agents other than clozapine compare with each other or first-generation antipsychotic agents, or how clozapine compares with other second-generation antipsychotic agents, because of a lack of evidence.
We don't know whether behavioural interventions, compliance therapy, psychoeducational interventions, or family interventions improve adherence to antipsychotic medication compared with usual care because of a paucity of good-quality evidence.
It is clear that some included studies in this review have serious failings and that the evidence base for the efficacy of antipsychotic medication and other interventions is surprisingly weak. For example, although in many trials haloperidol has been used as the standard comparator, the clinical trial evidence for haloperidol is less impressive may be expected.
By their very nature, systematic reviews and RCTs provide average indices of probable efficacy in groups of selected individuals. Although some RCTs limit inclusion criteria to a single category of diagnosis, many studies include individuals with different diagnoses such as schizoaffective disorder. In all RCTs, even in those recruiting people with a single DSM or ICD-10 diagnosis, there is considerable clinical heterogeneity.
Genome-wide association studies of large samples with schizophrenia demonstrate that this clinical heterogeneity reflects, in turn, complex biological heterogeneity. For example, genome-wide association studies suggest that around 1000 genetic variants of low penetrance and other individually rare genetic variants of higher penetrance, along with epistasis and epigenetic mechanisms, are thought to be responsible, probably with the biological and psychological effects of environmental factors, for the resultant complex clinical phenotype. A more stratified approach to clinical trials would help to identify those subgroups that seem to be the best responders to a particular intervention.
To date, however, there is little to suggest that stratification on the basis of clinical characteristics successfully helps to predict which drugs work best for which people. There is a pressing need for the development of biomarkers with clinical utility for mental health problems. Such measures could help to stratify clinical populations or provide better markers of efficacy in clinical trials, and would complement the current use of clinical outcome scales. Clinicians are also well aware that many people treated with antipsychotic medication develop significant adverse effects such as extrapyramidal symptoms or weight gain. Again, our ability to identify which people will develop which adverse effects is poorly developed, and might be assisted by using biomarkers to stratify populations.
The results of this review tend to indicate that as far as antipsychotic medication goes, current drugs are of limited efficacy in some people, and that most drugs cause adverse effects in most people. Although this is a rather downbeat conclusion, it should not be too surprising, given clinical experience and our knowledge of the pharmacology of the available antipsychotic medication. All currently available antipsychotic medications have the same putative mechanism of action — namely, dopaminergic antagonism with varying degrees of antagonism at other receptor sites. More efficacious antipsychotic medication awaits a better understanding of the biological pathogenesis of these conditions so that rational treatments can be developed.
PMCID: PMC3385413  PMID: 23870705
23.  Improving education and resources for health care providers. 
Environmental Health Perspectives  1993;101(Suppl 2):191-197.
Workers and citizens are turning increasingly to the health care system for information about occupational and environmental reproductive hazards, yet most primary care providers and specialists know little about the effects of occupational/environmental toxicants on the reproductive system or how to evaluate and manage patients at potential risk. Although it is unrealistic to expect all clinicians to become experts in this area, practitioners should know how to take a basic screening history, identify patients at potential risk, and make appropriate referrals. At present, occupational and environmental health issues are not well integrated into health professional education in the United States, and clinical information and referral resources pertaining to reproductive hazards are inadequate. In addressing these problems, the conference "Working Group on Health Provider Education and Resources" made several recommendations that are detailed in this report. Short-term goals include enhancement of existing expertise and resources at a regional level and better integration of information on occupational/environmental reproductive hazards into curricula, meetings, and publications of medical and nursing organizations. Longer term goals include development of a comprehensive, single-access information and referral system for clinicians and integration of occupational and environmental medicine into formal health professional education curricula at all levels.
PMCID: PMC1519936  PMID: 8243391
24.  Low Concordance With Guidelines for Treatment of Acute Cystitis in Primary Care 
Open Forum Infectious Diseases  2015;2(4):ofv159.
We found low concordance with the updated 2010 IDSA guidelines for both the choice of drug and duration of therapy for acute cystitis. Interventions to decrease overuse of fluoroquinolones are needed to preserve the antimicrobial efficacy of these important antimicrobials.
Background. The updated 2010 Infectious Diseases Society of America guidelines recommended 3 first-line therapies for uncomplicated cystitis: nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), and fosfomycin, while fluoroquinolones (FQs) remained as second-line agents. We assessed guideline concordance for antibiotic choice and treatment duration after introduction of the updated guidelines and studied patient characteristics associated with prescribing of specific antibiotics and with treatment duration.
Methods. We used the Epic Clarity database (electronic medical record system) to identify all female patients aged ≥18 years with uncomplicated cystitis in 2 private family medicine clinics in the period of 2011–2014. For each eligible visit, we extracted type of antibiotic prescribed, duration of treatment, and patient and visit characteristics.
Results. We included 1546 visits. Fluoroquinolones were the most common antibiotic class prescribed (51.6%), followed by nitrofurantoin (33.5%), TMP-SMX (12.0%), and other antibiotics (3.2%). A significant trend occurred toward increasing TMP-SMX and toward decreasing nitrofurantoin use. The duration of most prescriptions for TMP-SMX, nitrofurantoin, and FQs was longer than guidelines recommendations (longer durations were prescribed for these agents in 82%, 73%, and 71% of the prescriptions, respectively). No patient or visit characteristic was associated with use of specific antibiotics. Older age and presence of diabetes were independently associated with longer treatment duration.
Conclusions. We found low concordance with the updated guidelines for both the choice of drug and duration of therapy for uncomplicated cystitis in primary care. Identifying barriers to guideline adherence and designing interventions to decrease overuse of FQs may help preserve the antimicrobial efficacy of these important antimicrobials.
PMCID: PMC4675917  PMID: 26753168
antibacterial agents; guideline adherence; urinary tract infections
25.  The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the Non-Motor Symptoms of Parkinson's Disease 
The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Ω-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not useful for the above-mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short-term management of the different non-motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication-related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non-motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research.
PMCID: PMC4020145  PMID: 22021174
Parkinson's disease; evidence-based medicine; dopamine agonists; tricyclic antidepressants; selective serotonin reuptake inhibitors (SSRIs); omega-3 fatty-acids; transcranial magnetic stimulation

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