Search

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrőm macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response. Sixty treatment-naïve WM patients were enroled into this phase II trial and randomised (2:1) to receive cyclophosphamide and rituximab with either bortezomib (BRC) or fludarabine (FCR). The primary objective was to assess the overall response rate (ORR) in eligible patients receiving BRC (N= 41). An ORR of 97.6% (95%CI:87.1–99.9) was observed; 27 (65.9%) patients remain alive without progression after 62.6 months median follow-up, with 2-, 3- and 5-year progression-free survival (PFS) rates of 92.7% (95%CI:79.0–97.6), 80.5% (95%CI:64.8–89.7) and 65.5% (95%CI:48.8–77.9). Persistent WM B-cells were demonstrable in 19/38 patients at the end of treatment (median 0.24%, range 0.02–11.2%). PFS was markedly longer in patients with BM B-cell depletion (<0.004%) compared to those who had persistent BM B-cells detectable at end of treatment (HR = 0.06, 95%CI:0.01–0.47, p< 0.001), and remained independently associated after adjusting for baseline risk stratification or investigator-assessed response. BRC is a tolerable, highly efficacious regimen for treatment-naïve WM patients. BM B-cell depletion is independently associated with patient outcomes.

IntroductionThis study aimed to evaluate the impact of the helmet law on the changes in potential years of life lost (PYLL) due to traffic mortality and to examine modification effects of socioeconomic factors on the impacts in Vietnam.MethodsWe applied an interrupted time series design using the Bayesian framework to estimate the impact of the law at the provincial level. Then, we used random effects meta-analysis to estimate the impact of the law at the country level and to examine the modification effects of socioeconomic factors.ResultsThe results indicate that the impacts varied among the provinces. These impacts could be classified by four main groups comprising positive impact, and positive impact without sustainability, possible positive impact, negative or inconsistent impact. For the country-level impact, the results reveal a significantly consistent change in monthly PYLLs at the level of 18 per 100 000 persons, and the post-trend was stable without significant change. The results of meta-regression show that 1 unit increase in the population density (persons/km2), migration rate (%) and income (×1000 dong) are non-significantly associated with increases of PYLLs at 1.3, 27 and 27 per 100 000 person-months, respectively, whereas 1% increase in literacy associated with a decrease of PYLL at 44 per 100 000 person-months.DiscussionFurther studies should be warranted to provide a comprehensive evaluation of the law implementation, including its acceptability, adoption, appropriateness, feasibility, cost-effectiveness and sustainability.

Introduction

Introduction

Introduction

OBJECTIVES:Elevated serum immunoglobulin G4 (IgG4) levels have been associated with autoimmune pancreatitis and IgG4-related disease (IgG4-RD) for over a decade. However, an elevated serum IgG4 is not specific for the disease. There have been inconsistent reports of its use in diagnosis, as a marker of disease relapse, and its relationship to organ involvement in retrospective cohorts. The aims of this study were to ascertain conditions that are associated with an elevated serum IgG4 and to investigate the role of IgG4 in diagnosis, relapse, and organ involvement in a prospective cohort of patients with IgG4-RD.METHODS:We evaluated serum IgG4 measurements in the Oxford Immunology Laboratory over 6 years. Patients in whom serum IgG4 was requested to differentiate IgG4-RD from other diseases were recruited into a longitudinal follow-up study to determine final diagnosis. In a prospective cohort of IgG4-RD patients, organ involvement, response to therapy, and disease relapse were determined.RESULTS:Two thousand and sixty-seven samples from 1,510 patients had serum IgG4 measured. Of these, IgG4 was elevated (≥1.4 g l−1) in 243 (16.1%) patients. The main indication (85.6%) was to distinguish between IgG4-RD and non-IgG4-RD conditions. Only 5.1% of patients who had serum IgG4 measured for this purpose had a final diagnosis of IgG4-RD. Of those with an elevated serum IgG4, 22.4% met IgG4-RD diagnostic criteria. Serum IgG4 was elevated in 48 (82.8%) of IgG4-RD patients. An IgG4 cutoff of 1.4 g l−1gave a sensitivity of 82.8% and specificity of 84.7% to diagnose IgG4-RD. Increasing this to 2.8 g l−1increased specificity to 96.2% and negative predictive value to 97.7%, with a lower sensitivity of 56.9% and positive predictive value of 44.5%. Serum IgG4 levels fell with corticosteroid therapy, but this was not disease-specific. A serum IgG4 of ≥2.8 g l−1at diagnosis was associated with multi-organ involvement and risk of relapse.CONCLUSIONS:Serum IgG4 levels are elevated in multiple non-IgG4-RD inflammatory and malignant conditions, with less than one-quarter of those with an elevated IgG4 meeting IgG4-RD diagnostic criteria. A serum IgG4 of ≥2.8 g l−1is useful in distinguishing between IgG4-RD and non-IgG4-RD diagnoses, predicting multiple-organ involvement and risk of relapse in IgG4-RD.

Among children, infections with soil-transmitted helminths (STH) can cause anemia, impaired growth, and absence from school. Sustainable control of STH infection requires that appropriate latrines be integrated with health-promotion education. We report a pilot study of the effects of a combined latrine-education intervention in Central Java, Indonesia. The participants were 99 children (3–13 years old) in two villages (intervention and control) south of Semarang city. Stool samples were collected from the children and were examined for the presence of helminth eggs. After baseline data were collected, latrines were constructed and health education was given in the intervention village. Then, in both villages, all children who had STH infection at baseline were given 400 mg of albendazole. Eight months later, follow-up stool samples were collected and examined. In both villages, 20% of the children had STH infection at baseline. At follow-up, the incidence of STH infection was much lower in the intervention village than in the control village (4.0% vs. 20.4%; p<0.02). The results of this small pilot study give some confidence that a scaled-up study involving many more children and cluster-randomization of the intervention will be feasible and could provide more conclusive evidence of the intervention’s effectiveness.

Significant concentrations of PAHs and hydrocarbons were recorded in soil, beneath an asphalt cover. The site had not received any significant inputs from internal combustion vehicles and hence the contaminants would appear to have originated through leaching from the asphalt surface. PAH concentration in the soil samples was positively correlated with the moisture content at the site. A direct logarithmic relationship could be demonstrated between soil content of a particular PAH and molecular properties such as water solubility. The ratios between individual PAH concentrations at sites which had undergone different degrees of leaching also showed a linear logarithmic relationship to molecular descriptors such as connectivity index. It is suggested that a significant amount of PAH can enter the environment through leaching from asphalt surfaces. At least some of the roadside PAH contamination probably results from this pathway, in addition to deposition from exhaust fumes.

In the past, a variety of persistent organic chemicals (principally aldrin, dieldrin and coal tar), were placed in soil surrounding wooden power poles, in an attempt to control wood rotting organisms. With time, the chemicals have migrated both horizontally and vertically from the region of application, resulting in appreciable levels of these contaminants around power pole bases. The migration of the chemicals appears to be controlled by a number of factors including soil moisture status and solubility of the chemical. Dieldrin and the lower molecular weight PAHs show the greatest mobility. A significant conversion of aldrin to dieldrin was apparent in the upper layers of soil. It was found that the vertical and horizontal migration of the contaminants in soil correlated well with molecular descriptors such as water solubility and first order connectivity index.’