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Additional file 1: Supplementary Table. Countries of 751 unique authors of intervention systematic reviews in eyes and vision

Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group., The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

ObjectiveTo determine the feasibility, safety and tolerability of lumbar punctures (LPs) in research participants with early Parkinson disease (PD), subjects without evidence of dopaminergic deficiency (SWEDDs) and healthy volunteers (HC).BackgroundCerebrospinal fluid (CSF) analysis is becoming an essential part of the biomarkers discovery effort in PD with still limited data on safety and feasibility of serial LPs in PD participants.Design/methodsParkinson's Progression Marker Initiative (PPMI) is a longitudinal observation study designed to identify PD progression biomarkers. All PPMI participants undergo LP at baseline, 6, 12 months and yearly thereafter. CSF collection is performed by a trained investigator using predominantly atraumatic needles. Adverse events (AEs) are monitored by phone one week after LP completion. We analyzed safety data from baseline LPs.ResultsPPMI enrolled 683 participants (423 PD/196 HC/64 SWEDDs) from 23 study sites. CSF was collected at baseline in 97.5% of participants, of whom 5.4% underwent collection under fluoroscopy. 23% participants reported any related AEs, 68% of all AE were mild while 5.6% were severe. The most common AEs were headaches (13%) and low back pain (6.5%) and both occurred more commonly in HC and SWEDDs compared to PD participants. Factors associated with higher incidence of AEs across the cohorts included female gender, younger age and use of traumatic needles with larger diameter. AEs largely did not impact compliance with the future LPs.ConclusionsLPs are safe and feasible in PD research participants. Specific LP techniques (needle type and gauge) may reduce the overall incidence of AEs.

Este documento contiene archivo en PDF. El estudio realizado fue desde el punto de vista descriptivo, caracterizando los procesos peligrosos en los trabajadores que les lleva a padecer trastornos oculares, en el proyecto hidroeléctrico Minas San Francisco ubicado en la Provincia del Azuay. La población estuvo constituida por 150 obreros, que laboran en los 5 túneles: túnel de desvió, TBM, chimenea de equilibrio, de descarga y cuarto de máquinas. Los datos se recolectaron a través de cuatro instrumentos: una guía observacional, para identificar los procesos peligrosos del objeto, los medios, la actividad de trabajo y de los medios de protección; una guía de observación para identificar las condiciones ambientales del entorno; una encuesta individual, para la identificación de los procesos peligrosos de la organización y división del trabajo, y una historia clínica del médico ocupacional que recogió los trastornos a la salud. Los resultados obtenidos de los pacientes con afecciones oculares agudas, se dieron mayormente en obreros, ayudantes de los soldadores y soldadores y dependiendo el grado de la lesión con el descanso médico desde dos a tres días, lo que dificulta en mano de obra escasa; en cuanto a los equipos de protección personal se obtuvo ausencia de protectores oculares, auditivos, protectores respiratorios, en cuanto a organización y división del trabajo se encontró que laboran 8 horas/día, turnos diurnos y horas extras, ritmos de trabajo intensos y vigilancia estricta. This study was conducted from a descriptive point of view, characterizing dangerous processes in workers who leads them to suffer eye disorders in Minas San Francisco hydroelectric project located in the south-western boundary of the Province of Azuay. The target population consisted of 150 workers, who work in different confined spaces (tunnels) diversion tunnel, TBM, surge tank, tailrace tunnel, tunnel machine room. The data was collected through four instruments: an observational guide to identify dangerous processes of the object, the media, the work activity and means of protection; an observation guide to identify the environmental conditions; an individual survey, to identify dangerous processes of the organization and the work division, and a clinic history of the occupational doctor who collected health disorders. The results were obtained from patients with acute eye problems, mostly occurred in workers, welders and helpers welders and depending on the degree of injury with the medical permission for two to three days, making difficult the labor; in terms of personal protective equipment (PPA) there are not eye and hearing protection, respiratory protective devices are obtained, in terms of work organization and division found that in working 8 hours / day, day shifts and overtime, breaks according to work pace, rhythms of intense work and strict surveillance.

Summary Background Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. Methods We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). Findings In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900–0·946) with high sensitivity (0·834, 95% CI 0·711–0·883) and specificity (0·903, 95% CI 0·824–0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867–0·921) in the PDBP cohort, 0·998 (0·992–1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896–0·962) in LABS-PD, and 0·939 (0·891–0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Interpretation Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. Funding National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation.

This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls.Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10.Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD.This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy.

We aimed to assess the effects of childhood obesity prevention programmes on blood lipids in high-income countries. We searched MEDLINE®, Embase, PsychInfo, CINAHL®, clinicaltrials.gov, and the Cochrane Library up to 22 April 2013 for relevant randomized controlled trials, quasi-experimental studies and natural experiments published in English. Studies were included if they implemented diet and/or physical activity intervention(s) with ≥1 year follow-up (or ≥6 months for school-based intervention studies) in 2-18-year-olds, and were excluded if they targeted only overweight/obese children, or those with a pre-existing medical condition. Seventeen studies were finally included. For total cholesterol, the pooled intervention effect was -0.97 mg dL(-1) [95% confidence interval (CI): -3.26, 1.32; P = 0.408]; for low-density lipoprotein cholesterol (LDL-C), -6.06 mg dL(-1) (95% CI: -11.09, -1.02; P = 0.018); for high-density lipoprotein cholesterol (HDL-C), 1.87 mg dL(-1) (95% CI: 0.39, 3.34; P = 0.013); and for triglycerides, -1.95 mg dL(-1) (95% CI: -4.94, 1.04; P = 0.202). Most interventions (70%) showed similar significant or no effects on adiposity- and lipids outcomes: 15% interventions improved both adiposity- and lipids outcomes; 55% had no significant effects on either. Childhood obesity prevention programmes had a significant desirable effect on LDL-C and HDL-C. Two-thirds of interventions showed similar significant or no effects in adiposity- and lipids outcomes. Assessing lipids outcomes provide additional useful information on obesity prevention programme benefits.

Patients with cardiometabolic disease are at higher risk for obesity-related adverse effects. Even without weight loss, weight maintenance may be beneficial. We performed a systematic review to identify the effect of nonweight loss-focused lifestyle interventions in adults with cardiometabolic disease. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify comparative studies of lifestyle interventions (self-management, diet, exercise, or their combination) without a weight loss focus in adults with or at risk for diabetes and cardiovascular disease. Weight, BMI, and waist circumference at ≥12 months were the primary outcomes. Of 24,870 citations, we included 12 trials (self-management, n=2; diet, n=2; exercise, n=2; combination, n=6) studying 4,206 participants. Self-management plus physical activity ± diet versus minimal/no intervention avoided meaningful weight (−0.65 to −1.3 kg) and BMI (−0.4 to −0.7 kg/m2) increases. Self-management and/or physical activity prevented meaningful waist circumference increases versus control (−2 to −4 cm). In patients with cardiometabolic disease, self-management plus exercise may prevent weight and BMI increases and self-management and/or exercise may prevent waist circumference increases versus minimal/no intervention. Future studies should confirm these findings and evaluate additional risk factors and clinical outcomes.

To systematically review the evidence on the effectiveness of health care and palliative care interventions to improve outcomes for patients with advanced and serious illness.We searched MEDLINE®, CINAHL, PsycINFO, Cochrane, and DARE from 2000 through 2011. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts.We developed questions in collaboration with technical experts. We excluded retrospective and uncontrolled studies. Two investigators independently screened search results and abstracted data from eligible studies. We adapted previous frameworks to categorize included studies (e.g., by improvement target, setting). Because many studies did not report effect sizes and almost all studies were small (lt 200 studies), in order to be able to quantitatively describe the literature, we calculated the percentage of studies with a significant improvement in outcomes with the intervention compared to control group for each category. We also checked that all other studies did not report significant results in the opposite direction and checked that there were not differences between larger and smaller studies.We included 90 studies described in 96 articles. Of the 23 studies targeting continuity, coordination, and transitions, 33 percent of studies that evaluated quality of life as an outcome, 67 percent that evaluated patient satisfaction, and 31 percent that evaluated health care utilization (admissions and length of stay) found a statistically significant improvement with the intervention. Of the 21 studies targeting pain, almost all focused on patient education and self-management; 48 percent of them found a statistically significant improvement with the intervention. Findings for larger (100) and smaller (le 100) studies were similar. For distress, only 29 percent of the seven included studies found a statistically significant impact. Of the 20 studies in communication and decisionmaking, only 22 percent of studies addressing patient or family satisfaction found a statistically significant improvement for this outcome, compared to 73 percent for the outcome of health care utilization. We found only two studies within hospice programs, both of which found a statistically significant improvement in at least one outcome; nine studies were in nursing homes, 78 percent of which demonstrated a significant improvement with the intervention. In terms of types of quality improvement, for the target of continuity, studies including patient-centered quality improvement types, such as education and self-management, had the strongest evidence of effectiveness on patient- and family-centered domains such as satisfaction and quality of life. Studies of provider-focused interventions (e.g., education, reminders) were more likely to have an impact on health care utilization. Only one of five studies addressing multiple targets and focusing on facilitated relay of clinical data to providers demonstrated a statistically significant improvement in either quality of life or satisfaction. In terms of consultative and integrative interventions, for the target of communication and decisionmaking, three-quarters of consultative interventions showed a statistically significant improvement with the intervention, compared to half of integrative interventions. The literature was too heterogeneous and effect sizes were too infrequently reported for quantitative synthesis. There was moderate strength of evidence for the target of continuity, coordination, and transitions and the outcome of patient and caregiver satisfaction but low strength of evidence for other outcomes. For the target of pain, there was moderate strength of evidence for pain as an outcome. For the target of communication and decisionmaking, there was moderate strength of evidence for the outcome of health care utilization but low strength of evidence for other outcomes.We found that evidence was strongest (moderate strength of evidence) for interventions for pain, and for the targets of communication and decisionmaking and continuity for selected outcomes. While a few high- and medium-quality, well-designed health care and palliative care interventions have been conducted to improve outcomes for patients with advanced and serious illness, this report highlights the continued presence of variable findings, quality deficiencies, vaguely defined interventions, and variable outcome measurement tools and reporting in much of this intervention literature. The evidence has a number of gaps, including few studies in the hospice setting or pediatrics. Future research needs include techniques for improving recruitment and retention to assure adequate sample size, better development and description of interventions, and further development and standardization of outcome measures and tools.

Sham surgery controls are increasingly used in neurosurgical clinical trials in Parkinson's disease (PD) but remain controversial. We interviewed participants of such trials, specifically examining their understanding and attitudes regarding sham surgery.We conducted semistructured qualitative interviews with participants of 3 sham surgery-controlled trials for PD, focusing on their understanding of sham design, their reactions to it, its impact on decision making, and their understanding of posttrial availability of the experimental intervention and its impact on decisions to participate.All subjects (n = 90) understood the 2-arm design; most (86%) described the procedural differences between the arms accurately. Ninety-two percent referred to scientific or regulatory reasons as rationales for the sham control, with 62% specifically referring to the placebo effect. Ninety-one percent said posttrial availability of the experimental intervention had a strong (48%) or some (43%) influence on their decision to participate, but only 68% understood the conditions for posttrial availability.Most subjects in sham surgery-controlled PD trials comprehend the sham surgery design and its rationale. Although there is room for improvement, most subjects of sham surgery trials appear to be adequately informed.

The main objective of the report is to review the evidence on the impact of health information technology (IT) that supports patient-centered care (PCC) on: health care processes; clinical outcomes; intermediate outcomes (patient or provider satisfaction, health knowledge and behavior, and cost); responsiveness to needs and preferences of patients; shared decisionmaking and patient-clinician communication; and access to information. Additional objectives were to identify barriers and facilitators for using health IT to deliver PCC, and to identify gaps in evidence and information needed by patients, providers, payers, and policymakers.MEDLINE®, Embase®, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, INSPEC, and Compendex databases through July 31, 2010.Paired members of our team reviewed citations to identify randomized controlled trials of PCC-related health IT interventions and studies that addressed barriers and facilitators for health IT for delivery of PCC. Independent assessors rated studies for quality. Paired reviewers abstracted data.The search identified 327 eligible articles, including 184 articles on the impact of health IT applications implemented to support PCC and 206 articles addressing barriers or facilitators for such health IT applications. Sixty-three articles addressed both questions. The study results suggested positive effects of PCC-related health IT interventions on health care process outcomes, disease-specific clinical outcomes (for diabetes mellitus, heart disease, cancer, and other health conditions), intermediate outcomes, responsiveness to the needs and preferences of patients, shared decisionmaking, patient-clinician communication, and access to medical information. Studies reported a number of barriers and facilitators for using health IT applications to enable PCC. Barriers included: lack of usability; problems with access to the health IT application due to older age, low income, education, cognitive impairment, and other factors; low computer literacy in patients and clinicians; insufficient basic formal training in health IT applications; physicians' concerns about more work; workflow issues; problems related to new system implementation, including concerns about confidentiality of patient information; depersonalization; incompatibility with current health care practices; lack of standardization; and problems with reimbursement. Facilitators for the utilization of health IT included ease of use, perceived usefulness, efficiency of use, availability of support, comfort in use, and site location.Despite marked heterogeneity in study characteristics and quality, substantial evidence exists confirming that health IT applications with PCC-related components have a positive effect on health care outcomes. positive effect on health care outcomes.

To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support.We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts.Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles.We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies).There was a seven percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.

To synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea (HU) when used for treatment of sickle cell disease (SCD); and to review the evidence regarding barriers to its use.Articles cited in MEDLlNE, EMBASE, TOXLine, and CINAHL through June 30, 2007.Paired reviewers reviewed each title, abstract, and article to assess eligibility. They abstracted data sequentially and then independently graded the evidence.In one small, randomized trial of HU in children with SCD; the yearly hospitalization rate was lower with HU than placebo (1.1 versus 2.8, p=0.002). The absolute increase in fetal hemoglobin (Hb F%) was 10.7 percent. Twenty observational studies of HU in children reported similar increases in Hb F%, while hemoglobin concentration increased by roughly 1 g/dl. One large randomized trial tested the efficacy of HU in adults with SCD and found that after 2 years of treatment, Hb F% increased by 3.2 percent and hemoglobin increased by 0.6 g/dl, The median number of painful crises was 44 percent (p0.001) lower among patients treated with HU. The 12 observational studies of HU enrolling adults with SCD supported these findings. Panelists from the Center for the Evaluation of Risks to Human Reproduction reviewed the literature for potential toxicities of HU. They concluded that HU does not cause a growth delay in children 5-15 years old. There were no data on the effects on subsequent generations following exposure of developing germ cells to HU in utero. Some evidence supported impaired spermatogenesis with use of HU. Although we identified six patients taking HU who developed leukemia, the evidence did not support causality. Similarly, the evidence suggested no association between HU and leg ulcers in patients with SCD, although there was in patients with other illnesses. The literature supported neutropenia, skin rashes and nail changes associated with use of HU, but was sparse regarding skin neoplasms or other secondary malignancies in SCD. Only two studies investigated barriers to use of HU. Perceived efficacy and perceived safety of HU had the largest influence on patients' (or parents' ) choice to use HU. Providers reported barriers to be patient concerns about side effects; and their own concerns about HU in older patients, patient compliance, lack of contraception, side effects and carcinogenic potential, doubts about effectiveness, and concern about costs.HU is efficacious in children and adults with SCD; with an increase in Hb F%, and reduction in hospitalizations and pain crises. However, few studies have measured the effectiveness of HU for SCD in usual practice. The paucity of long-term studies limits conclusions about toxicities and about mortality. Future studies of interventions to overcome the barriers to use of HU in patients with SCD are necessary.