Symptomatic and asymptomatic secondary transmission of Cryptosporidium parvum following two related outbreaks in schoolchildren

Two related outbreaks (in 2009 and 2012) of cryptosporidiosis in Norwegian schoolchildren during a stay at a remote holiday farm provided us with a natural experiment to investigate possible secondary transmission of Cryptosporidium parvum IIa A19G1R1. After the children had returned home, clinical data and stool samples were obtained from their household contacts. Samples were investigated for the presence of Cryptosporidium oocysts by immunofluorescence antibody test. We found both asymptomatic and symptomatic infections, which are likely to have been secondary transmission. Laboratory-confirmed transmission rate was 17% [4/23, 95% confidence interval (CI) 7·0–37·1] in the 2009 outbreak, and 0% (95% CI 0–16·8) in the 2012 outbreak. Using a clinical definition, the probable secondary transmission rate in the 2012 outbreak was 8% (7/83, 95% CI 4·1–16·4). These findings highlight the importance of hygienic and public health measures during outbreaks or individual cases of cryptosporidiosis. We discuss our findings in light of previous studies reporting varying secondary transmission rates of Cryptosporidium spp

Circulating lipoprotein (a) and all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis.

AIMS To investigate the association between circulating lipoprotein(a) (Lp(a)) and risk of all-cause and cause-specific mortality in the general population and in patients with chronic diseases, and to elucidate the dose-response relations. METHODS AND RESULTS We searched literature to find prospective studies reporting adjusted risk estimates on the association of Lp(a) and mortality outcomes. Forty-three publications, reporting on 75 studies (957,253 participants), were included. The hazard ratios (HRs) and 95% confidence intervals (95%CI ) for the top versus bottom tertile of Lp(a) levels and risk of all-cause mortality were 1.09 (95%CI: 1.01-1.18, I2: 75.34%, n = 19) in the general population and 1.18 (95%CI: 1.04-1.34, I2: 52.5%, n = 12) in patients with cardiovascular diseases (CVD). The HRs for CVD mortality were 1.33 (95%CI: 1.11-1.58, I2: 82.8%, n = 31) in the general population, 1.25 (95%CI: 1.10-1.43, I2: 54.3%, n = 17) in patients with CVD and 2.53 (95%CI: 1.13-5.64, I2: 66%, n = 4) in patients with diabetes mellitus. Linear dose-response analyses revealed that each 50 mg/dL increase in Lp(a) levels was associated with 31% and 15% greater risk of CVD death in the general population and in patients with CVD. No non-linear dose-response association was observed between Lp(a) levels and risk of all-cause or CVD mortality in the general population or in patients with CVD (Pnonlinearity > 0.05). CONCLUSION This study provides further evidence that higher Lp(a) levels are associated with higher risk of all-cause mortality and CVD-death in the general population and in patients with CVD. These findings support the ESC/EAS Guidelines that recommend Lp(a) should be measured at least once in each adult person's lifetime, since our study suggests those with higher Lp(a) might also have higher risk of mortality

The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants

Background Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. Aims To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. Methods In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Results Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. Conclusion We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.publishedVersio

Molecular Imaging for Efficacy of Pharmacologic Intervention in Myocardial Remodeling

ObjectivesUsing molecular imaging techniques, we examined interstitial alterations during postmyocardial infarction (MI) remodeling and assessed the efficacy of antiangiotensin and antimineralocorticoid intervention, alone and in combination.BackgroundThe antagonists of the renin-angiotensin-aldosterone axis restrict myocardial fibrosis and cardiac remodeling after MI and contribute to improved survival. Radionuclide imaging with technetium-99m–labeled Cy5.5 RGD imaging peptide (CRIP) targets myofibroblasts and indirectly allows monitoring of the extent of collagen deposition post-MI.MethodsCRIP was intravenously administered for gamma imaging after 4 weeks of MI in 63 Swiss-Webster mice and in 6 unmanipulated mice. Of 63 animals, 50 were treated with captopril (C), losartan (L), spironolactone (S) alone, or in combination (CL, SC, SL, and SCL), 8 mice received no treatment. Echocardiography was performed for assessment of cardiac remodeling. Hearts were characterized histopathologically for the presence of myofibroblasts and thick and thin collagen fiber deposition.ResultsAcute MI size was similar in all groups. The quantitative CRIP percent injected dose per gram uptake was greatest in the infarct area of untreated control mice (2.30 ± 0.14%) and decreased significantly in animals treated with 1 agent (C, L, or S; 1.71 ± 0.35%; p = 0.0002). The addition of 2 (CL, SC, or SL 1.31 ± 0.40%; p < 0.0001) or 3 agents (SCL; 1.16 ± 0.26%; p < 0.0001) demonstrated further reduction in tracer uptake. The decrease in echocardiographic left ventricular function, strain and rotation parameters, as well as histologically verified deposition of thin collagen fibers, was significantly reduced in treatment groups and correlated with CRIP uptake.ConclusionsRadiolabeled CRIP allows for the evaluation of the efficacy of neurohumoral antagonists after MI and reconfirms superiority of combination therapy. If proven clinically, molecular imaging of the myocardial healing process may help plan an optimal treatment for patients susceptible to heart failure

Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study

Funding European Commission (DG-SANCO) , the International Agency for Research on Cancer (IARC) , MRC Early Career Fellowship (MR/M501669/1) .Background Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. Methods Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT–Lancet reference diet. Findings In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and allcause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10–1·16]) and between land use and all-cause mortality (1·18 [1·15–1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09–1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10–1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT–Lancet diet, we estimated that up to 19–63% of deaths and up to 10–39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT–Lancet reference diet. Additionally, switching from lower adherence to the EAT–Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. Interpretation Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health.European Commission European Commission Joint Research CentreWorld Health OrganizationUK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/M501669/

Prediagnosis Leisure-Time Physical Activity and Lung Cancer Survival: A Pooled Analysis of 11 Cohorts

Background: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisuretime physical activity (LTPA) with all-cause and lung cancer–specific mortality among incident lung cancer patients. Methods: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer–specific mortality after adjustment for major prognostic factors and lifetime smoking history. Results: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate ¼ 20.9%, 95% CI ¼ 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR ¼ 0.93, 95% CI ¼ 0.88 to 0.99), but not with lung cancer–specific mortality (multivariable-adjusted HR ¼ 0.99, 95% CI ¼ 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction ¼ .008 for all-cause mortality and .003 for lung cancer–specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariableadjusted HRs were 0.80 (95% CI¼ 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI¼ 0.65 to 0.99) for lung cancer–specific mortality. Conclusions: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer

Patient-reported outcomes in palliative gastrointestinal stenting: a Norwegian multicenter study

Background The clinical effect of stent treatment has been evaluated by mainly physicians; only a limited number of prospective studies have used patient-reported outcomes for this purpose. The aim of this work was to study the clinical effect of self-expanding metal stents in treatment of malignant gastrointestinal obstructions, as evaluated by patient-reported outcomes, and compare the rating of the treatment effect by patients and physicians. Methods Between November 2006 and April 2008, 273 patients treated with SEMS for malignant GI and biliary obstructions were recruited from nine Norwegian hospitals. Patients and physicians assessed symptoms independently at the time of treatment and after 2 weeks using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire supplemented with specific questions related to obstruction. Results A total of 162 patients (99 males; median age = 72 years) completed both assessments and were included in the study. A significant improvement in the mean global health score was observed after 2 weeks (from 9 to 18 on a 0–100 scale, P\0.03) for all stent locations. Both patients and physicians reported a significant reduction in all obstruction-related symptoms ([20 on the 0–100 scale, P\0.006) after SEMS treatment. The physicians reported a larger mean improvement in symptoms than did the patients, mainly because they reported more severe symptoms before treatment. Conclusion SEMS treatment is effective in relieving symptoms of malignant GI and biliary obstruction, as reported by patients and physicians. The physicians, however, reported a larger reduction in obstructive symptoms than did the patients. A prospective assessment of patientreported outcomes is important in evaluating SEMS treatment