Ambient temperature and cardiorespiratory morbidity : a systematic review and meta-analysis

BACKGROUND: The effect of extreme temperature has become an increasing public health concern. Evaluating the impact of ambient temperature on morbidity has received less attention than its impact on mortality. METHODS: We performed a systematic literature review and extracted quantitative estimates of the effects of hot temperatures on cardiorespiratory morbidity. There were too few studies on effects of cold temperatures to warrant a summary. Pooled estimates of effects of heat were calculated using a Bayesian hierarchical approach that allowed multiple results to be included from the same study, particularly results at different latitudes and with varying lagged effects. RESULTS: Twenty-one studies were included in the final meta-analysis. The pooled results suggest an increase of 3.2% (95% posterior interval = -3.2% to 10.1%) in respiratory morbidity with 1°C increase on hot days. No apparent association was observed for cardiovascular morbidity (-0.5% [-3.0% to 2.1%]). The length of lags had inconsistent effects on the risk of respiratory and cardiovascular morbidity, whereas latitude had little effect on either. CONCLUSIONS: The effects of temperature on cardiorespiratory morbidity seemed to be smaller and more variable than previous findings related to mortality.

FluMum : a prospective cohort study of mother-infant pairs assessing the effectiveness of maternal influenza vaccination in prevention of influenza in early infancy

INTRODUCTION Influenza vaccination in pregnancy is recommended for all women in Australia, particularly those who will be in their second or third trimester during the influenza season. However, there has been no systematic monitoring of influenza vaccine uptake among pregnant women in Australia. Evidence is emerging of benefit to the infant with respect to preventing influenza infection in the first 6 months of life. The FluMum study aims to systematically monitor influenza vaccine uptake during pregnancy in Australia and determine the effectiveness of maternal vaccination in preventing laboratory-confirmed influenza in their offspring up to 6 months of age. METHODS AND ANALYSIS A prospective cohort study of 10 106 mother-infant pairs recruited between 38 weeks gestation and 55 days postdelivery in six Australian capital cities. Detailed maternal and infant information is collected at enrolment, including influenza illness and vaccination history with a follow-up data collection time point at infant age 6 months. The primary outcome is laboratory-confirmed influenza in the infant. Case ascertainment occurs through searches of Australian notifiable diseases data sets once the infant turns 6 months of age (with parental consent). The primary analysis involves calculating vaccine effectiveness against laboratory-confirmed influenza by comparing the incidence of influenza in infants of vaccinated mothers to the incidence in infants of unvaccinated mothers. Secondary analyses include annual and pooled estimates of the proportion of mothers vaccinated during pregnancy, the effectiveness of maternal vaccination in preventing hospitalisation for acute respiratory illness and modelling to assess the determinants of vaccination. ETHICS AND DISSEMINATION The study was approved by all institutional Human Research Ethics Committees responsible for participating sites. Study findings will be published in peer review journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER The study is registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR) number: 12612000175875.

Health states for schizophrenia and bipolar disorder within the Global Burden of Disease 2010 Study

A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Prevalence of foot disease and risk factors in general inpatient populations: A systematic review and meta-analysis

Objective: To systematically review studies reporting the prevalence in general adult inpatient populations of foot disease disorders (foot wounds, foot infections, collective ‘foot disease’) and risk factors (peripheral arterial disease (PAD), peripheral neuropathy (PN), foot deformity). Methods: A systematic review of studies published between 1980 and 2013 was undertaken using electronic databases (MEDLINE, EMBASE and CINAHL). Keywords and synonyms relating to prevalence, inpatients, foot disease disorders and risk factors were used. Studies reporting foot disease or risk factor prevalence data in general inpatient populations were included. Included study's reference lists and citations were searched and experts consulted to identify additional relevant studies. 2 authors, blinded to each other, assessed the methodological quality of included studies. Applicable data were extracted by 1 author and checked by a second author. Prevalence proportions and SEs were calculated for all included studies. Pooled prevalence estimates were calculated using random-effects models where 3 eligible studies were available. Results: Of the 4972 studies initially identified, 78 studies reporting 84 different cohorts (total 60 231 517 participants) were included. Foot disease prevalence included: foot wounds 0.01–13.5% (70 cohorts), foot infections 0.05–6.4% (7 cohorts), collective foot disease 0.2–11.9% (12 cohorts). Risk factor prevalence included: PAD 0.01–36.0% (10 cohorts), PN 0.003–2.8% (6 cohorts), foot deformity was not reported. Pooled prevalence estimates were only able to be calculated for pressure ulcer-related foot wounds 4.6% (95% CI 3.7% to 5.4%)), diabetes-related foot wounds 2.4% (1.5% to 3.4%), diabetes-related foot infections 3.4% (0.2% to 6.5%), diabetes-related foot disease 4.7% (0.3% to 9.2%). Heterogeneity was high in all pooled estimates (I2=94.2–97.8%, p<0.001). Conclusions: This review found high heterogeneity, yet suggests foot disease was present in 1 in every 20 inpatients and a major risk factor in 1 in 3 inpatients. These findings are likely an underestimate and more robust studies are required to provide more precise estimates.

Return to sport after open and microdiscectomy surgery versus conservative treatment for lumbar disc herniation: a systematic review with meta-analysis.

BACKGROUND: Lumbar disc herniation has a prevalence of up to 58% in the athletic population. Lumbar discectomy is a common surgical procedure to alleviate pain and disability in athletes. We systematically reviewed the current clinical evidence regarding athlete return to sport (RTS) following lumbar discectomy compared to conservative treatment. METHODS: A computer-assisted literature search of MEDLINE, CINAHL, Web of Science, PEDro, OVID and PubMed databases (from inception to August 2015) was utilised using keywords related to lumbar disc herniation and surgery. The design of this systematic review was developed using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Methodological quality of individual studies was assessed using the Downs and Black scale (0-16 points). RESULTS: The search strategy revealed 14 articles. Downs and Black quality scores were generally low with no articles in this review earning a high-quality rating, only 5 articles earning a moderate quality rating and 9 of the 14 articles earning a low-quality rating. The pooled RTS for surgical intervention of all included studies was 81% (95% CI 76% to 86%) with significant heterogeneity (I(2)=63.4%, p<0.001) although pooled estimates report only 59% RTS at same level. Pooled analysis showed no difference in RTS rate between surgical (84% (95% CI 77% to 90%)) and conservative intervention (76% (95% CI 56% to 92%); p=0.33). CONCLUSIONS: Studies comparing surgical versus conservative treatment found no significant difference between groups regarding RTS. Not all athletes that RTS return at the level of participation they performed at prior to surgery. Owing to the heterogeneity and low methodological quality of included studies, rates of RTS cannot be accurately determined.

Can physical activity modulate pancreatic cancer risk?:a systematic review and meta-analysis

Numerous epidemiological studies have examined the association between physical activity and pancreatic cancer; however, findings from individual cohorts have largely not corroborated a protective effect. Among other plausible mechanisms, physical activity may reduce abdominal fat depots inducing metabolic improvements in glucose tolerance and insulin sensitivity, thereby potentially attenuating pancreatic cancer risk. We performed a systematic review to examine associations between physical activity and pancreatic cancer. Six electronic databases were searched from their inception through July 2009, including MEDLINE and EMBASE, seeking observational studies examining any physical activity measure with pancreatic cancer incidence/mortality as an outcome. A random effects model was used to pool individual effect estimates evaluating highest vs. lowest categories of activity. Twenty-eight studies were included. Pooled estimates indicated a reduction in pancreatic cancer risk with higher levels of total (five prospective studies, RR: 0.72, 95% CI: 0.52-0.99) and occupational activity (four prospective studies, RR: 0.75, 95% CI: 0.59-0.96). Nonsignificant inverse associations were seen between risks and recreational and transport physical activity. When examining exercise intensity, moderate activity appeared more protective (RR: 0.79, 95% CI: 0.52-1.20) than vigorous activity (RR: 0.97, 95% CI: 0.85-1.11), but results were not statistically significant and the former activity variable incorporated marked heterogeneity. Despite indications of an inverse relationship with higher levels of work and total activity, there was little evidence of such associations with recreational and other activity exposures.

The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: A systematic review and meta-analysis

Barrett's esophagus is a well-recognized precursor of esophageal adenocarcinoma. Surveillance of Barrett's esophagus patients is recommended to detect high-grade dysplasia (HGD) or early cancer. Because of wide variation in the published cancer incidence in Barrett's esophagus, the authors undertook a systematic review and meta-analysis of cancer and HGD incidence in Barrett's esophagus. Ovid Medline (Ovid Technologies, Inc., New York, New York) and EMBASE (Elsevier, Amsterdam, the Netherlands) databases were searched for papers published between 1950 and 2006 that reported the cancer/HGD risk in Barrett's esophagus. Where possible, early incident cancers/HGD were excluded, as were patients with HGD at baseline. Forty-seven studies were included in the main analysis, and the pooled estimate for cancer incidence in Barrett's esophagus was 6.1/1,000 person-years, 5.3/1,000 person-years when early incident cancers were excluded, and 4.1/1,000 person-years when both early incident cancer and HGD at baseline were excluded. Corresponding figures for combined HGD/cancer incidence were 10.0 person-years, 9.3 person-years, and 9.1/1,000 person-years. Compared with women, men progressed to cancer at twice the rate. Cancer or HGD/cancer incidences were lower when only high-quality studies were analyzed (3.9/1,000 person-years and 7.7/1,000 person-years, respectively). The pooled estimates of cancer and HGD incidence were low, suggesting that the cost-effectiveness of surveillance is questionable unless it can be targeted to those with the highest cancer risk.

Dietary fiber and the risk of precancerous lesions and cancer of the esophagus:a systematic review and meta-analysis

Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.

Prevalence and risk factors of depressive symptoms in a Canadian palliative home care population: a cross-sectional study

Background: Depression in palliative care patients is important because of its intrinsic burden and association with elevated physical symptoms, reduced immunity and increased mortality risk. Identifying risk factors associated with depression can enable clinicians to more readily diagnose it, which is important since depression is treatable. The purpose of this cross-sectional study was to determine the prevalence of depressive symptoms and risk factors associated with them in a large sample of palliative home care patients.

Methods: The data come from interRAI Palliative Care assessments completed between 2006 and 2012. The sample (n = 5144) consists of adults residing in Ontario (Canada), receiving home care services, classified as palliative, and not experiencing significant cognitive impairment. Logistic regression identified the risk factors associated with depressive symptoms. The dependent variable was the Depression Rating Scale (DRS) and the independent variables were functional indicators from the interRAI assessment and other variables identified in the literature. We examined the results of the complete case and multiple imputation analyses, and found them to be similar.

Results: The prevalence of depressive symptoms was 9.8%. The risk factors associated with depressive symptoms were (pooled estimates, multiple imputation): low life satisfaction (OR = 3.01 [CI = 2.37-3.82]), severe and moderate sleep disorders (2.56 [2.05-3.19] and 1.56 [1.18-2.06]), health instability (2.12 [1.42-3.18]), caregiver distress 2.01 [1.62-2.51]), daily pain (1.73 [1.35-2.22]), cognitive impairment (1.45 [1.13-1.87]), being female (1.37 [1.11-1.68]), and gastrointestinal symptoms (1.27 [1.03-1.55]). Life satisfaction mediated the effect of prognostic awareness on depressive symptoms.

Conclusions: The prevalence of depressive symptoms in our study was close to the median of 10-20% reported in the palliative care literature, suggesting they are present but by no means inevitable in palliative patients. Most of the factors associated with depressive symptoms in our study are amenable to clinical intervention and often targeted in palliative care programs. Designing interventions to address them can be challenging, however, requiring careful attention to patient preferences, the spectrum of comorbid conditions they face, and their social supports. Life satisfaction was one of the strongest factors associated with depressive symptoms in our study, and is likely to be among the most challenging to address.

Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration:a systematic review and economic evaluation

BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.

OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.

DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).

REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.

INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).

COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.

RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£44,649; QALYs 10.575; incremental cost-effectiveness ratio £47,768). The least costly strategy had a 46.4% probability of being cost-effective at £30,000 willingness-to-pay threshold.

LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.

CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Recipient obesity and outcomes after kidney transplantation: a systematic review and meta-analysis

BACKGROUND: The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation.

METHODS: A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m(2). Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m(2)). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated.

RESULTS: Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83 416) and an increased likelihood of DGF (OR = 1.68, 95% CI = 1.39-2.03, studies = 4, n = 28 847).

CONCLUSIONS: Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.

A systematic review of population based epidemiological studies in Myasthenia Gravis

Background: The aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed.

Methods: Studies were identified using multiple sources and meta-analysis performed to calculate pooled estimates for IR, PR and MR.

Results: 55 studies performed between 1950 and 2007 were included, representing 1.7 billion population-years. For All MG estimated pooled IR (eIR): 5.3 per million person-years (C.I.: 4.4, 6.1), range: 1.7 to 21.3; estimated pooled PR: 77.7 per illion persons (C.I.: 64.0, 94.3), range 15 to 179; MR range 0.1 to 0.9 per millions person-years. AChR MG eIR: 7.3 (C.I.: 5.5, 7.8), range: 4.3 to 18.0; MuSK MG IR range: 0.1 to 0.32. However marked variation persisted between populations studied with similar methodology and in similar areas.

Conclusions: We report marked variation in observed frequencies of MG. We show evidence of increasing frequency of MG with year of study and improved study quality. This probably reflects improved case ascertainment. But other factors must also influence disease onset resulting in the observed variation in IR across geographically and genetically similar populations.

Meta-análise de parâmetros genéticos relacionados ao consumo alimentar residual e a suas características componentes em bovinos

The objective of this work was to estimate, by meta-analysis, the heritability (h(2)) and the genetic (r(g)) and phenotypic (r(f)) correlations of residual feed intake (RFI), and of its component traits in beef cattle from 19 breeds or genetic groups. Twenty-two scientific papers published from 1963 to 2011, from eight countries, totaling 52,637 cattle of ages from 28 days up to slaughter, were evaluated. The estimates of RFI, dry matter intake (DMI), average daily gain (ADG) and metabolic weight (BW0.75) were weighted by the inverse of sample variance. The variation between studies of h(2) for each trait was analyzed by weighted least squares. The effects of sex, country and breed were significant for h(2) of RFI, explaining 67% of variation between studies. For DMI, country and breed effects were significant and explained 96% of variation. Pooled estimates of h(2) were: 0.255+/-0.008, 0.278+/-0.012, 0.321+/-0.015, and 0.397+/-0.032 for RFI, DMI, ADG and BW0.75, respectively. Pooled estimates of genetic and phenotypic correlations were low between RFI and ADG and between RFI and BW0.75 (from -0.021+/-0.034 to 0.025+/-0.035), and moderate between RFI and DMI (0.636+/-0.035 and 0.698+/-0.041) and between DMI, ADG and BW0.75 (0.441+/-0.062 to 0.688+/-0.032). The trait RFI has lower heritability estimates than its components.