Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies

Delli AJ, Lindblad B, Carlsson A, Forsander G, Ivarsson S‐A, Ludvigsson J, Marcus C, Lernmark Å; for the Better Diabetes Diagnosis (BDD) Study Group. Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies. Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients <18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non‐Swedish, and Mixed‐origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen‐2 autoantibodies (IA‐2Ab)]. Results: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non‐Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21–23) patients/10⁵/yr rate for Swedish patients compared with 14 (95% CI: 13–15) among non‐Swedish patients. The HLA‐DQ8 haplotype (p < 0.0001) and DQ2/8 genotype (p < 0.02) predominated among Swedish compared with non‐Swedish patients. In contrast, DQ2 was the most frequent haplotype among non‐Swedish patients [OR = 1.5 (95% CI: 1.0–2.0), p < 0.04]. Multiple (≥2) autoantibodies (p < 0.04) and specifically IA‐2Ab (p < 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p < 0.001). Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA‐DQ2 genetic markers and are diagnosed more often with GAD65Ab.     

Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ

Lung function, smoking, age and mortality data in 158 adult severe alpha₁-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV₁ value was significantly associated with increased mortality (p < 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV₁ values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV₁ values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV₁ levels (p = 0.008) and higher mortality (p < 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV₁ level were not statistically significant (p = 0.9 and p>0.25, respectively). Cross-sectional analysis of the initial FEV₁ values indicated a significant decline (p < 0.005) of FEV₁ with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV₁ rates of decline in 80 cases with follow-up FEV₁ measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.     

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin‐dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose–insulin–glucagon model was used to describe seven virtual patients with insulin pump‐treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba‐insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre‐defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin levels, regardless of how insulin was estimated. A 125‐μg glucagon dose was needed to optimally treat mild hypoglycaemia when insulin levels were equal to baseline levels. In contrast, glucagon doses >500 μg were needed when se/ba‐insulin >2.5, IOB >2.0 U or IOB/TDD >6%. Although the proposed model‐based glucagon regimen needs confirmation in clinical trials, this is the first attempt to develop an insulin‐dependent glucagon dosing regimen for treatment of insulin‐induced mild hypoglycaemia in patients with type 1 diabetes.     

新注射吸毒者及长期注射吸毒者共用针具的影响因素分析

目的 了解新注射吸毒者和长期注射吸毒者共用针具的影响因素.方法 对四川省注射吸毒者进行社区横断面调查.结果 3852名被调查者中,注射吸毒史<1年、1～3年和>3年者最近6个月共用针具比例依次为19.9%、29.1%和36.3%.注射吸毒<1年的被调查者共用针具的独市影响因素包括女性、少数民族、注射吸毒频率高、共用注射器/针头以外其他吸毒用具、有非同定性伴、固定性伴注射吸毒、未自愿做过艾滋病检测、招募年、招募地区;注射吸毒1～3年的被凋查者共用针具的独立影响因素包括文化程度低、注射频率高、共用注射器/针头以外其他吸毒用具、有非固定性伴、固定性伴注射吸毒、未使用安全套、未参与技能培训、招募年、招募地区;注射吸毒>3年的被调奋者共用针具的独立影响因素包括文化程度低、注射频牢高、共用注射器/针头以外其他吸毒用具、有非同定性伴、有商业性伴、固定性伴注射吸毒、未使用安全套、未参与针具交换、招募年、招募地区.结论 新注射吸毒者和长期注射吸毒者共用针具及无保护性行为比例均较高,长期注射吸毒者较新注射吸毒者有更多共用针具行为和无保护性行为,针对两类人群的干预应有不同侧重.     

Douching beliefs and practices among black and white women

To ascertain beliefs about douching, douching practices, and their motivational antecedents among adult women living in the southeastern United States, we conducted a telephone survey of a random sample of 535 adult women. Douching was deemed a good hygienic practice by 65% of women, half of whom believed that douching was necessary for good hygiene. These beliefs were more common among black than white women. Older women and less educated women were more likely to believe that douching prevented infections and pregnancies. Physicians were the only discouraging influence regarding douching reported by a substantial proportion of the women. Healthcare providers' advice not to douche is correlated with not douching. Encouragement by mother (OR = 4.7, 95% CI 1.9-11.4), being black (OR = 2.8, 95% CI 1.1-6.9), and having no more than a high school education (OR = 2.2, 95% CI 1.2-4.2) were independently associated with ever (vs. never) douching. A substantial proportion of adult women living in the southeastern United States believe that douching is necessary for good hygiene. Our findings suggest that advice from healthcare providers to discourage the practice may have a salutary effect.     

Seasonal variation of lead uptake in the earthworm Lumbricus terrestris and the influence of soil liming and acidification

The influence of seasonal temperature variations and liming and acidification of the soil on lead uptake in juveniles and adults of the earthworm species Lumbricus terrestris L. was studied by enclosing specimens for up to five months in net bags provided with lead-contaminated, sandy soil. Lead concentrations were analyzed in the pharynx, gizzard, muscles, seminal vesicles and cerebral ganglion. Lead distribution in whole animals was assessed after an injection of ²⁰³Pb. The lead concentrations of the tissues were mostly linearly correlated with the soil concentrations, which ranged from <0.5 to 310 mg/kg, and the highest concentrations were generally found in the ganglion. The effects on lead concentrations in tissues of lowered soil pH from 5.6 to 5.1 or raised to 5.9 were insignificant, though more lead became allocated to muscles than to ganglion when pH was lowered. The lead uptake was strongly dependent on the ambient temperature, especially in the muscles, and the concentrations were reduced by 50% or more during the cold spell in the winter season, presumably as a consequence of a low feeding activity. Though juveniles seemed more prone to take up lead, the concentrations were not significantly higher than those in adults during the winter period. The observations are discussed in the light of the use of earthworms in standardized programs for environmental hazard assessment, especially with respect to species and tissue selection.     

Radium-223 dichloride for the treatment of bone metastatic castration-resistant prostate cancer: an evaluation of its safety

Introduction: Approximately 10 – 20% of prostate cancer cases ultimately progress to castration-resistant prostate cancer (CRPC), for which there is a poor prognosis and a therapeutic need. Radium-223 dichloride (radium-223 [Xofigo]) is a first-in-class α-emitting radiopharmaceutical shown to significantly prolong overall survival in patients with CRPC with symptomatic bone metastases and no visceral metastases. Current treatment guidelines recommended it in both pre- and post-docetaxel settings.

Areas covered: Radium-223 mechanism of action, pharmacokinetics and key efficacy and safety data are reviewed. The evaluation of adverse events reported in the Phase III ALSYMPCA trial is summarized for the overall population and patient subpopulations (prior docetaxel, concomitant external beam radiation therapy and baseline opioid use). An evaluation of how radium-223 is being incorporated into the CRPC treatment paradigm and the implications of its safety profile for future use are provided.

Expert opinion: The pronounced efficacy and safety profile of radium-223 positions it as a valuable new therapeutic tool in the CRPC armamentarium. Its novel mechanism of action underlies low rates of hematologic adverse events. Radium-223 treatment will become common in the majority of pre-docetaxel symptomatic CRPC cases, as it has proved to be highly efficient with few safety concerns earlier in the course of disease.     

A long-term prospective study of optic neuritis: evaluation of risk factors

Eighty-six patients with monosymptomatic optic neuritis of unknown cause were followed prospectively for a median period of 12.9 years. At onset, cerebrospinal fluid (CSF) pleocytosis was present in 46 patients (53%) but oligoclonal immunoglobulin in only 40 (47%) of the patients. The human leukocyte antigen (HLA)-DR2 was present in 45 (52%). Clinically definite multiple sclerosis (MS) was established in 33 patients. Actuarial analysis showed that the cumulative probability of developing MS within 15 years was 45%. Three risk factors were identified: low age and abnormal CSF at onset, and early recurrence of optic neuritis. Female gender, onset in the winter season, and the presence of HLA-DR2 antigen increased the risk for MS, but not significantly. Magnetic resonance imaging detected bilateral discrete white matter lesions, similar to those in MS, in 11 of 25 patients, 7 to 18 years after the isolated attack of optic neuritis. Nine were among the 13 with abnormal CSF and only 2 belonged to the group of 12 with normal CSF (p = 0.01). Normal CSF at the onset of optic neuritis conferred better prognosis but did not preclude the development of MS.