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Subject(s)
Antitubercular Agents , Tuberculosis, Ocular , Humans , Western Australia/epidemiology , Retrospective Studies , Female , Male , Antitubercular Agents/administration & dosage , Tuberculosis, Ocular/drug therapy , Tuberculosis, Ocular/diagnosis , Adult , Middle Aged , Aged , Young Adult , Treatment Outcome , Adolescent , Retinal Vasculitis/diagnosis , Retinal Vasculitis/drug therapy , Follow-Up StudiesABSTRACT
The ocean is a valuable natural resource that contains numerous biologically active compounds with various bioactivities. The marine environment comprises unexplored sources that can be utilized to isolate novel compounds with bioactive properties. Marine cyanobacteria are an excellent source of bioactive compounds that have applications in human health, biofuel, cosmetics, and bioremediation. These cyanobacteria exhibit bioactive properties such as anti-inflammatory, anti-cancer, anti-bacterial, anti-parasitic, anti-diabetic, anti-viral, antioxidant, anti-aging, and anti-obesity effects, making them promising candidates for drug development. In recent decades, researchers have focused on isolating novel bioactive compounds from different marine cyanobacteria species for the development of therapeutics for various diseases that affect human health. This review provides an update on recent studies that explore the bioactive properties of marine cyanobacteria, with a particular focus on their potential use in human health applications.
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Wolbachia is an insect endosymbiont being used for biological control in the mosquito Aedes aegypti because it causes cytoplasmic incompatibility (CI) and limits viral replication of dengue, chikungunya, and Zika viruses. While the genetic mechanism of pathogen blocking (PB) is not fully understood, the strength of both CI and PB are positively correlated with Wolbachia densities in the host. Wolbachia densities are determined by a combination of Wolbachia strain and insect genotype, as well as interactions with the environment. We employed both artificial selection and inbreeding with the goal of creating lines of Ae. aegypti with heritable and distinct Wolbachia densities so that we might better dissect the mechanism underlying PB. We were unable to shift the mean relative Wolbachia density in Ae. aegypti lines by either strategy, with relative densities instead tending to cycle over a narrow range. In lieu of this, we used Wolbachia densities in mosquito legs as predictors of relative densities in the remaining individual's carcass. Because we worked with outbred mosquitoes, our findings indicate either a lack of genetic variation in the mosquito for controlling relative density, natural selection against extreme densities, or a predominance of environmental factors affecting densities. Our study reveals that there are moderating forces acting on relative Wolbachia densities that may help to stabilize density phenotypes post field release. We also show a means to accurately bin vector carcasses into high and low categories for non-DNA omics-based studies of Wolbachia-mediated traits.
Subject(s)
Aedes , Wolbachia , Zika Virus Infection , Zika Virus , Aedes/genetics , Animals , Mosquito Vectors/genetics , Specific Gravity , Virus Replication , Wolbachia/geneticsABSTRACT
BACKGROUND: Australia has a low incidence of TB and has committed to eliminating the disease. Identification of risk factors associated with TB is critical to achieving this goal.METHODS: We undertook a prospective cohort study involving persons receiving TB treatment in four Australian jurisdictions. Risk factors and their association with delayed treatment completion (treatment delayed by at least 1 month) were analysed using univariate analyses and multivariate logistic regression.RESULTS: Baseline surveys were completed for 402 persons with TB. Most (86.1%) were born overseas. Exposure to a person with TB was reported by 19.4%. Diabetes mellitus (10.2%), homelessness (9.2%), cigarette smoking (8.7%), excess alcohol consumption (6.0%) and mental illness (6.2%) were other common risk factors. At follow-up, 24.8% of patients had delayed treatment completion, which was associated with adverse events (34.1%, aOR 6.67, 95% CI 3.36-13.27), excess alcohol consumption (6.0%, aOR 21.94, 95% CI 6.03-79.85) and HIV co-infection (2.7%, aOR 8.10, 95% CI 1.16-56.60).CONCLUSIONS: We identified risk factors for TB and their association with delayed treatment completion, not all of which are routinely collected for surveillance purposes. Recognition of these risk factors should facilitate patient-centred care and assist Australia in reaching TB elimination.
Subject(s)
HIV Infections , Tuberculosis , Australia/epidemiology , HIV Infections/epidemiology , Humans , Prospective Studies , Risk Factors , Time-to-Treatment , Tuberculosis/complications , Tuberculosis/epidemiologyABSTRACT
BACKGROUND: The insect endosymbiotic bacterium Wolbachia is being deployed in field populations of the mosquito Aedes aegypti for biological control. This microbe prevents the replication of human disease-causing viruses inside the vector, including dengue, Zika and chikungunya. Relative Wolbachia densities may in part predict the strength of this 'viral blocking' effect. Additionally, Wolbachia densities may affect the strength of the reproductive manipulations it induces, including cytoplasmic incompatibility (CI), maternal inheritance rates or induced fitness effects in the insect host. High rates of CI and maternal inheritance and low rates of fitness effects are also key to the successful spreading of Wolbachia through vector populations and its successful use in biocontrol. The factors that control Wolbachia densities are not completely understood. METHODS: We used quantitative PCR-based methods to estimate relative density of the Wolbachia wAlbB strain in both the somatic and reproductive tissues of adult male and female mosquitoes, as well as in eggs. Using correlation analyses, we assessed whether densities in one tissue predict those in others within the same individual, but also across generations. RESULTS: We found little relationship among the relative Wolbachia densities of different tissues in the same host. The results also show that there was very little relationship between Wolbachia densities in parents and those in offspring, both in the same and different tissues. The one exception was with ovary-egg relationships, where there was a strong positive association. Relative Wolbachia densities in reproductive tissues were always greater than those in the somatic tissues. Additionally, the densities were consistent in females over their lifetime regardless of tissue, whereas they were generally higher and more variable in males, particularly in the testes. CONCLUSIONS: Our results indicate that either stochastic processes or local tissue-based physiologies are more likely factors dictating Wolbachia densities in Ae. aegypti individuals, rather than shared embryonic environments or heritable genetic effects of the mosquito genome. These findings have implications for understanding how relative Wolbachia densities may evolve and/or be maintained over the long term in Ae. aegypti.
Subject(s)
Aedes , Wolbachia , Zika Virus Infection , Zika Virus , Aedes/physiology , Animals , Female , Humans , Male , Mosquito Vectors/physiology , Specific Gravity , Wolbachia/physiologyABSTRACT
Maternal anaphylaxis is rare albeit life-threatening critical incident dreaded by many due to negative effects on not only the mother but the foetus as well. Antibiotics and anaesthetic agents still contribute to majority of the episodes. Consequences of anaphylaxis such as placental insufficiency and subsequent foetal neurocognitive deficits are devastating outcomes. Acute respiratory distress syndrome following anaphylaxis is even rarer among the normal population. The management of maternal anaphylaxis does not differ from routine recommendations even though close monitoring and preparedness for early delivery should be embedded in the protocols. This is a rare case report of a primi mother who developed anaphylactic shock following intravenous penicillin in the background of negative allergic history, resultant foetal distress requiring emergency lower segment caesarian section and delayed onset acute respiratory distress syndrome which was later attributed to anaphylaxis. Pertinent identification and management which included a multidisciplinary team culminated in favourable outcomes.
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BACKGROUND: During fetal surgery, the haemodynamic stability of the fetus depends on the haemodynamic stability of the mother. The primary objective of this study was to assess changes in fetal heart rate (FHR) throughout the different stages of surgery. The secondary objective was to assess potential changes in maternal physiological parameters and their association with FHR. METHODS: This was a single-center observational cohort study conducted between 2015 and 2019 in 26 women undergoing intra-uterine fetoscopic repair of open spina bifida. The primary outcome was FHR. Maternal physiologic parameters were measured at the beginning, during and after surgery. The linear mixed-effects model fitted by maximum likelihood was used to assess changes in each variable at specific times throughout the surgery, and the repeated measures correlation coefficient was used to study the association between FHR and maternal physiological parameters. RESULTS: One (3.8%) case of fetal bradycardia (FHR <110â¯beats per minute) required the administration of intramuscular atropine. No other significant FHR changes were observed during surgery. Maternal oesophageal temperature (Pâ¯<0.001), lactate levels (P=0.002), and mean arterial pressure (P=0.016) changed significantly during surgery, although none of these changes was clinically relevant. The FHR showed a significant association with maternal carbon dioxide tension (r=0.285, 95% CI 0.001 to 0.526) and maternal heart rate (r=0.302, 95% CI 0.025 to 0.535). CONCLUSION: The FHR remained stable during intra-uterine fetoscopic repair of open spina bifida. Maternal carbon dioxide tension and heart rate may have a mild influence on FHR.
Subject(s)
Heart Rate, Fetal , Neural Tube Defects , Cohort Studies , Female , Fetal Monitoring , Fetoscopy , Heart Rate , Humans , Monitoring, Physiologic , Neural Tube Defects/surgery , PregnancyABSTRACT
Spotted fever group (SFG) rickettsiae are obligatory intracellular bacteria that cause disease in humans and other animals. Ixodid ticks are the principal vectors of SFG rickettsiae. The present study aimed to determine the prevalence and species identity of SFG rickettsiae in ticks and horses from urban and rural areas of western Cuba using PCR assays. Tick samples, collected from 79 horses, consisted of 14 Amblyomma mixtum adults, 111 Dermacentor nitens adults and 19 pools of D. nitens nymphs (2-5 individuals/pool). The PCR results revealed the presence of Rickettsia spp. in 64% of the A. mixtum adults, 16% of the D. nitens adults, and 11% of the pooled samples of D. nitens nymphs. In contrast, Rickettsia spp. was not detected in any of the 200 horse blood samples included in this study. DNA sequence data of the rickettsial 17 kDa antigen gene showed that Rickettsia amblyommatis was present in A. mixtum; and Rickettsia felis in D. nitens. This is the first report of R. felis in D. nitens in Cuba. The present study extends our knowledge of the potential vector spectrum and distribution of SFG rickettsiae pathogens in western Cuba.
Subject(s)
Horses , Ixodidae/microbiology , Rickettsia , Spotted Fever Group Rickettsiosis/veterinary , Amblyomma/microbiology , Animals , Arachnid Vectors/microbiology , Cuba/epidemiology , DNA, Bacterial/genetics , Dermacentor/microbiology , Horse Diseases/microbiology , Horses/microbiology , Horses/parasitology , Nymph/microbiology , Pathology, Molecular , Polymerase Chain Reaction/veterinary , Rickettsia/genetics , Rickettsia/isolation & purification , Spotted Fever Group Rickettsiosis/epidemiology , Spotted Fever Group Rickettsiosis/microbiology , Tick Infestations/veterinaryABSTRACT
Epizootic ulcerative syndrome (EUS), caused by the water mould (Oomycota) Aphanomyces invadans, has spread throughout the world's major continents over the last 50 years, with the apparent exception of South and Central America. With over 160 susceptible fish species representing 54 families and 16 orders recorded to date, EUS is of international concern and infection with A. invadans is a World Organisation for Animal Health (OIE) listed disease. This paper examines what little has been reported on the impacts of EUS on subsistence fisheries and wildlife, or what can be deduced about those impacts, and concludes that there is a need for systematic data collection on the size and socio-economic importance of subsistence fisheries. Such fisheries are often relied upon by the poorest communities, thus food and nutrition security impacts can be significant. Similarly, impacts on wildlife are poorly documented, emphasising the lack of, and the need for, research on and modelling of the ecosystem-level impacts of EUS and other aquatic animal diseases. The history of EUS and several other aquatic animal diseases also brings into question the effectiveness of current measures for controlling the international spread of aquatic animal diseases and calls for a re-think on how best to meet this ongoing challenge.
En l'espace d'un demi-siècle, le syndrome ulcératif épizootique dû à l'oomycète Aphanomyces invadans s'est propagé dans toutes les régions du monde, à l'exception, semble-t-il, de l'Amérique du Sud et Centrale. Avec plus de 160 espèces de poissons répertoriées comme sensibles, réparties en 54 familles et 16 ordres, le syndrome ulcératif épizootique est une maladie préoccupante à l'échelle internationale et figure parmi les maladies listées par l'Organisation mondiale de la santé animale (OIE) sous le nom d'infection à A. invadans. Les auteurs font état des très rares signalements concernant l'impact du syndrome ulcératif épizootique sur la pêche de subsistance et sur la faune sauvage et tentent d'en tirer quelques conclusions, en insistant sur la nécessité de procéder à une collecte systématique de données afin de déterminer l'envergure et l'importance socioéconomique de la pêche de subsistance. Les communautés les plus pauvres étant souvent celles qui dépendent le plus de cette activité, la maladie a sans doute un impact majeur sur la sécurité alimentaire et nutritionnelle de ces populations. De même, l'impact sur la faune sauvage n'a pas vraiment été étudié jusqu'à présent, d'où la nécessité de conduire des travaux de recherche et de modélisation sur l'impact du syndrome ulcératif épizootique (et d'autres maladies des animaux aquatiques) à l'échelle des écosystèmes. L'histoire du syndrome ulcératif épizootique et d'autres maladies des animaux aquatiques pose également la question de l'efficacité des mesures appliquées actuellement pour maîtriser la propagation internationale de ces maladies et invite à repenser la réponse à apporter à ce défi toujours présent.
En los últimos 50 años, el síndrome ulcerante epizoótico, causado por el hongo acuático (oomiceto) Aphanomyces invadans, se ha diseminado por casi todos los continentes del planeta, con la aparente salvedad de Sudamérica y Centroamérica. Se trata de una enfermedad de importancia internacional que, hasta donde consta a día de hoy, afecta a más de 160 especies piscícolas de 54 familias y 16 órdenes. De ahí que la infección por A. invadans sea una patología inscrita en la lista de la Organización Mundial de Sanidad Animal (OIE). Los autores, tras exponer lo poco que hasta ahora se ha descrito de los efectos de la enfermedad sobre la pesca de subsistencia y la fauna silvestre o lo que es posible inferir acerca de esos efectos, llegan a la conclusión de que se requiere una labor sistemática de obtención de datos sobre la magnitud e importancia socioeconómica de la actividad pesquera de subsistencia, de la que dependen a menudo las comunidades más pobres, por lo que las consecuencias para la seguridad nutricional y alimentaria pueden ser de calado. Tampoco están bien descritas las repercusiones de la enfermedad en los animales silvestres, lo que pone de relieve la ausencia, y por ende la necesidad, de investigaciones y de modelos sobre los efectos ecosistémicos del síndrome ulcerante epizoótico y otras varias enfermedades de los animales acuáticos. La historia de estas patologías también arroja dudas sobre la eficacia de las medidas aplicadas actualmente para controlar la propagación internacional de las enfermedades de los animales acuáticos y exige replantearse cuál es la respuesta idónea a este problema que no cesa.
Subject(s)
Animals, Wild/microbiology , Aphanomyces , Fish Diseases , Fisheries , Animals , Ecosystem , Fish Diseases/epidemiology , Fish Diseases/microbiology , FishesABSTRACT
OBJECTIVES: This study examined ninety-day and one-year postoperative healthcare utilization and costs following total knee arthroplasty (TKA) from the health sector and patient perspectives. DESIGN: This study relied on: 1) patient-reported medical resource utilization data from diaries in the Knee Arthroplasty Pain Coping Skills Training (KASTPain) trial; and 2) Medicare fee schedules. Medicare payments, patient cost-sharing, and patient time costs were estimated. Generalized linear mixed models were used to identify baseline predictors of costs. RESULTS: In the first ninety days following TKA, patients had an average of 29.7 outpatient visits and 6% were hospitalized. Mean total costs during this period summed to $3,720, the majority attributed to outpatient visit costs (84%). Over the year following TKA, patients had an average of 48.9 outpatient visits, including 33.2 for physical therapy. About a quarter (24%) of patients were hospitalized. Medical costs were incurred at a decreasing rate, from $2,428 in the first six weeks to $648 in the last six weeks. Mean total medical costs across all patients over the year were $8,930, including $5,328 in outpatient costs. Total costs were positively associated with baseline Charlson comorbidity score (P < 0.01). Outpatient costs were positively associated with baseline Charlson comorbidity score (P = 0.03) and a bodily pain burden summary score (P < 0.01). Mean patient cost-sharing summed to $1,342 and time costs summed to $1,346. CONCLUSIONS: Costs in the ninety days and year after TKA can be substantial for both healthcare payers and patients. These costs should be considered as payers continue to explore alternative payment models.
Subject(s)
Aftercare/economics , Arthroplasty, Replacement, Knee/economics , Health Care Costs , Patient Acceptance of Health Care/statistics & numerical data , Aged , Female , Humans , Male , Middle Aged , Time FactorsABSTRACT
OBJECTIVE: Knee arthroplasty (KA) is an effective surgical procedure. However, clinical studies suggest that a considerable number of patients continue to experience substantial pain and functional loss following surgical recovery. We aimed to estimate pain and function outcome trajectory types for persons undergoing KA, and to determine the relationship between pain and function trajectory types, and pre-surgery predictors of trajectory types. DESIGN: Participants were 384 patients who took part in the KA Skills Training randomized clinical trial. Pain and function were assessed at 2-week pre- and 2-, 6-, and 12-months post-surgery. Piecewise latent class growth models were used to estimate pain and function trajectories. Pre-surgery variables were used to predict trajectory types. RESULTS: There was strong evidence for two trajectory types, labeled as good and poor, for both Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Function scores. Model estimated rates of the poor trajectory type were 18% for pain and function. Dumenci's latent kappa between pain and function trajectory types was 0.71 (95% CI: 0.61-0.80). Pain catastrophizing and number of painful body regions were significant predictors of poor pain and function outcomes. Outcome-specific predictors included low income for poor pain and baseline pain and younger age for poor function. CONCLUSIONS: Among adults undergoing KA, approximately one-fifth continue to have persistent pain, poor function, or both. Although the poor pain and function trajectory types tend to go together within persons, a significant number experience either poor pain or function but not both, suggesting heterogeneity among persons who do not fully benefit from KA.
Subject(s)
Arthroplasty, Replacement, Knee/rehabilitation , Osteoarthritis, Knee/surgery , Pain/etiology , Age Factors , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Models, Statistical , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/rehabilitation , Pain/physiopathology , Pain Measurement/methods , Postoperative Period , Prognosis , Recovery of Function , Risk Factors , Severity of Illness Index , Socioeconomic Factors , Treatment OutcomeABSTRACT
BACKGROUND: Equine influenza virus (EIV) is one of the main causes of viral respiratory affections in horses. Little is known about the prevalence of EIV in Saudi Arabia especially the H3N8 serotype. OBJECTIVES: To assess prevalence of equine influenza in horse populations in Eastern and Central Saudi Arabia. STUDY DESIGN: Cross-sectional study. METHODS: We collected 145 sera, 323 nasal and 323 rectal swabs from horses from six major cities in Eastern and Central regions. None of the horses were vaccinated against EIV. Sera were tested in ELISA assays for influenza A type-specific antibodies and by haemagglutination inhibition (HI) tests using equine H3N8. The swabs were tested by RT-qPCR assay targeting a conserved region of the influenza A matrix gene that detects influenza A viruses of all subtypes. RESULTS: None of the swabs had detectable influenza A virus RNA. Of the 145 serasamples tested by ELISA, 81 (55.9%) were positive and 98 (67.6%) of 145 sera tested by HI tests were positive for equine H3. MAIN LIMITATIONS: Our failure to detect and sequence any EIV prevents identification of the lineage of virus that circulates in the Kingdom of Saudi Arabia. CONCLUSIONS: These results confirm that EIV H3N8 is circulating in Saudi Arabia and should be considered as a possible cause when investigating horses with respiratory disease in Saudi Arabia.
Subject(s)
Antibodies, Viral/blood , Horse Diseases/virology , Influenza A Virus, H3N8 Subtype , Orthomyxoviridae Infections/veterinary , Animals , Horse Diseases/epidemiology , Horses , Orthomyxoviridae Infections/blood , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Saudi Arabia/epidemiology , Seroepidemiologic StudiesABSTRACT
OBJECTIVE: Accurate prediction of abdominal aortic aneurysm (AAA) growth in an individual can allow personalised stratification of surveillance intervals and better inform the timing for surgery. The authors recently described the novel significant association between flow mediated dilatation (FMD) and future AAA growth. The feasibility of predicting future AAA growth was explored in individual patients using a set of benchmark machine learning techniques. METHODS: The Oxford Abdominal Aortic Aneurysm Study (OxAAA) prospectively recruited AAA patients undergoing the routine NHS management pathway. In addition to the AAA diameter, FMD was systemically measured in these patients. A benchmark machine learning technique (non-linear Kernel support vector regression) was applied to predict future AAA growth in individual patients, using their baseline FMD and AAA diameter as input variables. RESULTS: Prospective growth data were recorded at 12 months (360 ± 49 days) in 94 patients. Of these, growth data were further recorded at 24 months (718 ± 81 days) in 79 patients. The average growth in AAA diameter was 3.4% at 12 months, and 2.8% per year at 24 months. The algorithm predicted the individual's AAA diameter to within 2 mm error in 85% and 71% of patients at 12 and 24 months. CONCLUSIONS: The data highlight the utility of FMD as a biomarker for AAA and the value of machine learning techniques for AAA research in the new era of precision medicine.
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OBJECTIVES: To determine the association between the quality of guidelines for diagnostic tests (both the quality and reporting and the quality of the evidence underpinning recommendations) and nonadherence. STUDY DESIGN AND SETTING: We conducted a meta-epidemiological study. We previously published a systematic review that quantified the percentage of test use that was nonadherent with guidelines. For the present study, we assessed these guidelines using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool. We then assessed the quality of evidence underpinning recommendations within these guidelines using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Linear models were then constructed to determine the association between guideline nonadherence and (1) AGREE II score and (2) GRADE score. RESULTS: There was no significant association between AGREE II score and nonadherent testing (P = 0.09). There was a significant association between GRADE score and nonadherence: recommendations based on low-quality and very low-quality evidence had 38% (P < 0.01) and 24% (P = 0.02) more nonadherent testing, compared with recommendations based on high-quality evidence. CONCLUSION: Diagnostic test guideline recommendations based on high-quality evidence are adhered to more frequently.
Subject(s)
Diagnostic Tests, Routine , Evidence-Based Medicine/methods , Guideline Adherence/statistics & numerical data , Practice Guidelines as Topic/standards , Diagnostic Tests, Routine/methods , Diagnostic Tests, Routine/standards , Epidemiologic Studies , Humans , Quality Assurance, Health Care , Research DesignSubject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/economics , Diabetes Mellitus, Type 1/epidemiology , Health Services Accessibility/statistics & numerical data , Insurance, Health, Reimbursement/statistics & numerical data , Administrative Claims, Healthcare/statistics & numerical data , Blood Glucose/metabolism , Blood Glucose Self-Monitoring/economics , Blood Glucose Self-Monitoring/instrumentation , Blood Glucose Self-Monitoring/statistics & numerical data , Cost-Benefit Analysis , Diabetes Mellitus, Type 1/drug therapy , England/epidemiology , Healthcare Disparities/economics , Healthcare Disparities/statistics & numerical data , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/economics , Insulin/administration & dosage , Insulin/economics , Insulin Infusion Systems/economics , Insulin Infusion Systems/statistics & numerical data , Longitudinal StudiesABSTRACT
BACKGROUND: Most guidelines recommend that patients who have undergone curative resection for primary colorectal cancer are followed up for 5 years with regular blood carcinoembryonic antigen (CEA) tests to trigger further investigation for recurrence. However, CEA may miss recurrences, or patients may have false alarms and undergo unnecessary investigation. METHODS: The diagnostic accuracy of trends in CEA measurements for recurrent colorectal cancer, taken as part of the FACS (Follow-up After Colorectal Surgery) trial (2003-2014), were analysed. Investigation to detect recurrence was triggered by clinical symptoms, scheduled CT or colonoscopy, or a CEA level of at least 7 µg/l above baseline. Time-dependent receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic accuracy of CEA trends with single measurements. CEA trends were estimated using linear regression. RESULTS: The area under the ROC curve (AUC) for CEA trend was at least 0·820 across all 5 years of follow-up. In comparison, the AUCs for single measurements ranged from 0·623 to 0·749. Improvement was most marked at the end of the first year of follow-up, with the AUC increasing from 0·623 (95 per cent c.i. 0·509 to 0·736) to 0·880 (0·814 to 0·947). However, no individual trend threshold achieved a sensitivity above 70 per cent (30 per cent missed recurrences). CONCLUSION: Interpreting trends in CEA measurements instead of single CEA test results improves diagnostic accuracy for recurrence, but not sufficiently to warrant it being used as a single surveillance strategy to trigger further investigation. In the absence of a more accurate biomarker, monitoring trends in CEA should be combined with clinical, endoscopic and imaging surveillance for improved accuracy.
Subject(s)
Carcinoembryonic Antigen/blood , Colorectal Neoplasms/diagnosis , Neoplasm Recurrence, Local/diagnosis , Aged , Aged, 80 and over , Colorectal Neoplasms/blood , Colorectal Neoplasms/surgery , Humans , Linear Models , Middle Aged , Neoplasm Recurrence, Local/blood , ROC Curve , Reproducibility of ResultsABSTRACT
OBJECTIVES: Systematic reviews and meta-analysis are the standard methods to assess the association between prognostic markers and major events/conditions. However, the summary measures reported are not always explicitly presented and therefore different indirect methods of extracting estimates have been proposed. The aim of this study is to present two new alternative methods for obtaining summary statistics to be included in a meta-analysis of prognostic studies based on simulating individual patient data and to compare them with the already known generalized least squares for trend (glst) estimation method and direct method. STUDY DESIGN AND SETTINGS: We have checked the performance of these methods using a between study comparison, including 122 studies, and a within study comparison, based on data from one of the studies. RESULTS: The results obtained in this study show that glst estimation method appears to overestimate the effect size when reported information is incomplete. For the within-study comparison, the closest approximation to the direct estimates was obtained using the approach based on simulating individual patient data. CONCLUSION: The proposed simulation methods are a good alternative when other well-known indirect methods cannot be used.
Subject(s)
Data Analysis , Least-Squares Analysis , Meta-Analysis as Topic , Prognosis , Systematic Reviews as TopicABSTRACT
BACKGROUND: Unexpected weight loss is a symptom of serious disease in primary care, for example between 1 in 200 and 1 in 30 patients with unexpected weight loss go on to develop cancer. However, it remains unclear how and when general practitioners (GPs) should investigate unexpected weight loss. Without clarification, GPs may wait too long before referring (choosing to watch and wait and potentially missing a diagnosis) or not long enough (overburdening hospital services and exposing patients to the risks of investigation). The overall aim of this study is to provide the evidence necessary to allow GPs to more effectively manage patients with unexpected weight loss. METHODS: A retrospective cohort analysis of UK Clinical Practice Research Datalink (CPRD) data to: (1) describe how often in UK primary care the symptom of reported weight loss is coded, when weight is measured, and how GPs respond to a patient attending with unexpected weight loss; (2) identify the predictive value of recorded weight loss for cancer and serious disease in primary care, using cumulative incidence plots to compare outcomes between subgroups and Cox regression to explore and adjust for covariates. Preliminary work in CPRD estimates that weight loss as a symptom is recorded for approximately 148,000 eligible patients > 18 years and is distributed evenly across decades of age, providing adequate statistical power and precision in relation to cancer overall and common cancers individually. Further stratification by cancer stage will be attempted but may not be possible as not all practices within CPRD are eligible for cancer registry linkage, and staging information is often incomplete. The feasibility of using multiple imputation to address missing covariate values will be explored. DISCUSSION: This will be the largest reported retrospective cohort of primary care patients with weight measurements and unexpected weight loss codes used to understand the association between weight measurement, unexpected weight loss, and serious disease including cancer. Our findings will directly inform international guidelines for the management of unexpected weight loss in primary care populations.