Is Childhood Immune Thrombocytopenia Associated With Acquired Toxoplasmosis? An Unusual Case of Infection That Led to Acute ITP in a Greek Male Toddler and Implications for Guidelines.

INTRODUCTION: Childhood immune thrombocytopenic purpura (ITP) is a heterogeneous immune-mediated process triggered by infections, vaccines, allergies and parasites. Currently, there is little evidence in the literature beyond case reports of an association with Toxoplasma gondii (T. gondii). METHODS: The authors describe the unusual case of an earlier healthy 2.5-year-old Greek boy who developed acute ITP with a life-threatening platelet count a few days after a T. gondii infection. Evidence for the infection onset was found incidentally 3 months after the initial admission to the hospital and only after any other plausible cause of thrombocytopenia was excluded, according to diagnosis guidelines. RESULTS: The boy underwent 3 intravenous immunoglobulin treatments within a trimester, a period during which his alarming platelets count levels led to housebound activities. A quite slow recovery was only ignited after the third treatment, which was administered in conjunction with a mild antibiotic medication for the T. gondii infection. Full recovery was obtained 9 months after the initial admission, although the boy's potential scored high in clinical prediction models for developing transient ITP. CONCLUSION: There is a need for more research on ITPs with no obvious cause to investigate a causal association with toxoplasmosis. Currently, testing for diseases of greater rarity and of higher diagnostic cost than T. gondii is included in the ITP guidelines. Hence, routinely testing for toxoplasmosis when considering potential childhood ITP triggers and infection treatment complementary to treating the ITP might be the key to accelerating the healing process and improving the quality of life of otherwise confined children.

Heterogeneity in meta-analysis: a comprehensive overview.

In recent years, meta-analysis has evolved to a critically important field of Statistics, and has significant applications in Medicine and Health Sciences. In this work we briefly present existing methodologies to conduct meta-analysis along with any discussion and recent developments accompanying them. Undoubtedly, studies brought together in a systematic review will differ in one way or another. This yields a considerable amount of variability, any kind of which may be termed heterogeneity. To this end, reports of meta-analyses commonly present a statistical test of heterogeneity when attempting to establish whether the included studies are indeed similar in terms of the reported output or not. We intend to provide an overview of the topic, discuss the potential sources of heterogeneity commonly met in the literature and provide useful guidelines on how to address this issue and to detect heterogeneity. Moreover, we review the recent developments in the Bayesian approach along with the various graphical tools and statistical software that are currently available to the analyst. In addition, we discuss sensitivity analysis issues and other approaches of understanding the causes of heterogeneity. Finally, we explore heterogeneity in meta-analysis for time to event data in a nutshell, pointing out its unique characteristics.

Depression as a Risk Factor for the Initial Presentation of Twelve Cardiac, Cerebrovascular, and Peripheral Arterial Diseases: Data Linkage Study of 1.9 Million Women and Men.

BACKGROUND: Depression is associated with coronary heart disease and stroke, but associations with a range of pathologically diverse cardiovascular diseases are not well understood. We examine the risk of 12 cardiovascular diseases according to depression status (history or new onset). METHODS: Cohort study of 1,937,360 adult men and women, free from cardiovascular disease at baseline, using linked UK electronic health records between 1997 and 2010. The exposures were new-onset depression (a new GP diagnosis of depression and/or prescription for antidepressants during a one-year baseline), and history of GP-diagnosed depression before baseline. The primary endpoint was initial presentation of 12 cardiovascular diseases after baseline. We used disease-specific Cox proportional hazards models with multiple imputation adjusting for cardiovascular risk factors (age, sex, socioeconomic status, smoking, blood pressure, diabetes, cholesterol). RESULTS: Over a median [IQR] 6.9 [2.1-10.5] years of follow-up, 18.9% had a history of depression and 94,432 incident cardiovascular events occurred. After adjustment for cardiovascular risk factors, history of depression was associated with: stable angina (Hazard Ratio = 1.38, 95%CI 1.32-1.45), unstable angina (1.70, 1.60-1.82), myocardial infarction (1.21, 1.16-1.27), unheralded coronary death (1.23, 1.14-1.32), heart failure (1.18, 1.13-1.24), cardiac arrest (1.14, 1.03-1.26), transient ischemic attack (1.31, 1.25-1.38), ischemic stroke (1.26, 1.18-1.34), subarachnoid haemorrhage (1.17, 1.01-1.35), intracerebral haemorrhage (1.30, 1.17-1.45), peripheral arterial disease (1.24, 1.18-1.30), and abdominal aortic aneurysm (1.12,1.01-1.24). New onset depression developed in 2.9% of people, among whom 63,761 cardiovascular events occurred. New onset depression was similarly associated with each of the 12 diseases, with no evidence of stronger associations compared to history of depression. The strength of association between depression and these cardiovascular diseases did not differ between women and men. CONCLUSION: Depression was prospectively associated with cardiac, cerebrovascular, and peripheral diseases, with no evidence of disease specificity. Further research is needed in understanding the specific pathophysiology of heart and vascular disease triggered by depression in healthy populations.

Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England.

INTRODUCTION: While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range. METHODS: CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models. RESULTS: The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18), heart failure (IRR = 1.61, 95%CI 1.43-1.83), cardiac arrest (HR = 2.26, 95%CI 1.69-3.02) and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age. CONCLUSIONS: The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis.

Associations between polymyalgia rheumatica and giant cell arteritis and 12 cardiovascular diseases.

OBJECTIVES: Evidence of the association of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) with the full range of cardiovascular diseases (CVDs) is limited. We examined their relationship with the first clinical presentation of the 12 most common CVDs in an unselected population-based cohort of men and women. METHODS: We analysed CArdiovascular disease research using LInked Bespoke studies and Electronic health Records (CALIBER) data, which links primary care and hospital and mortality data in England, from 1997 to 2010. We assembled a cohort of men and women initially free from CVD at baseline and included all patients with PMR and/or GCA (PMR/GCA) diagnosis, matched by age, sex and general practice with up to 10 individuals without PMR/GCA. Random effects Poisson regression analysis was used to study the association between PMR/GCA and the initial presentation of 12 types of CVDs. RESULTS: The analysis included 9776 patients with PMR only, 1164 with GCA only, 627 with PMR and GCA and 105 504 without either condition. During a median of 3.14 years of follow-up 2787 (24.1%) individuals with PMR/GCA and 21 559 (20.4%) without PMR/GCA developed CVDs. Patients with PMR/GCA had lower rates of unheralded coronary death (3.18 vs 3.61/1000 person-years; adjusted incidence ratio 0.79, 95% CI 0.66 to 0.95), transient ischaemic attack (5.11 vs 5.61/1000 person-years; 0.67, 95% CI 0.54 to 0.84) and coronary and death composite (24.17 vs 25.80/1000 person-years; 0.90, 95% CI 0.82 to 0.98). No associations were observed for other CVDs or cerebrovascular diseases, and in patients with only PMR or GCA. No evidence of interaction by age or sex was found. Estimates decreased with longer PMR/GCA duration and findings were robust to multiple sensitivity analyses. CONCLUSIONS: In this large contemporary population-based cohort the presence of PMR and/or GCA was not associated with an increased risk of CVDs or cerebrovascular diseases regardless of PMR/GCA duration.

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction.

AIMS: To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. METHODS AND RESULTS: We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002-11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04-1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21-1.96)]. CONCLUSION: The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.

Nuclear grade plus proliferation grading system for invasive ductal carcinoma of the breast: validation in a tertiary referral hospital cohort.

OBJECTIVES: For patients with invasive breast cancer, management decisions are informed by tumor grade according to the Nottingham Grading System (NGS), either on its own or as part of the Nottingham Prognostic Index (NPI). A system retaining the nuclear grade element but substituting the two subjective components, mitosis count and tubule formation, of the NGS with a proliferation index based on Ki-67 (MIB-1) has been proposed (nuclear grade plus proliferation [N+P] grading). METHODS: We validated the prognostic value of this grading system on a population of 322 women. RESULTS: N+P grading resulted in more grade I tumors (47.9% vs 4.5%) and fewer grade II (32% vs 51.5%) and grade III (20.1% vs 44%) tumors compared with NGS. The NPI calculated based on N+P grade had a similar association with survival (P < .001; odds ratio, 1.729) as the NPI calculated on the basis of the NGS grade (P < .001; odds ratio, 1.668). CONCLUSIONS: The N+P system seems equivalent to the NGS system.

Socioeconomic deprivation and the incidence of 12 cardiovascular diseases in 1.9 million women and men: implications for risk prediction and prevention.

BACKGROUND: Recent experimental evidence suggests that socioeconomic characteristics of neighbourhoods influence cardiovascular health, but observational studies which examine deprivation across a wide range of cardiovascular diseases (CVDs) are lacking. METHODS: Record-linkage cohort study of 1.93 million people to examine the association between small-area socioeconomic deprivation and 12 CVDs. Health records covered primary care, hospital admissions, a myocardial infarction registry and cause-specific mortality in England (CALIBER). Patients were aged ≥30 years and were initially free of CVD. Cox proportional hazard models stratified by general practice were used. FINDINGS: During a median follow-up of 5.5 years 114,859 people had one of 12 initial CVD presentations. In women the hazards of all CVDs except abdominal aortic aneurysm increased linearly with higher small-area socioeconomic deprivation (adjusted HR for most vs. least deprived ranged from 1.05, 95%CI 0.83-1.32 for abdominal aortic aneurysm to 1.55, 95%CI 1.42-1.70 for heart failure; I2 = 81.9%, τ2 = 0.01). In men heterogeneity was higher (HR ranged from 0.89, 95%CI 0.75-1.06 for cardiac arrest to 1.85, 95%CI 1.67-2.04 for peripheral arterial disease; I2 = 96.0%, τ2 = 0.06) and no association was observed with stable angina, sudden cardiac death, subarachnoid haemorrhage, transient ischaemic attack and abdominal aortic aneurysm. Lifetime risk difference between least and most deprived quintiles was most marked for peripheral arterial disease in women (4.3% least deprived, 5.8% most deprived) and men (4.6% least deprived, 7.8% in most deprived); but it was small or negligible for sudden cardiac death, transient ischaemic attack, abdominal aortic aneurysm and ischaemic and intracerebral haemorrhage, in both women and men. CONCLUSIONS: Associations of small-area socioeconomic deprivation with 12 types of CVDs were heterogeneous, and in men absent for several diseases. Findings suggest that policies to reduce deprivation may impact more strongly on heart failure and peripheral arterial disease, and might be more effective in women.