Age-Related Differences in the Frequency of Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents

OBJECTIVE

We studied the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in children in Finland.

RESEARCH DESIGN AND METHODS

From 2002 to 2005, data on virtually all children <15 years of age diagnosed with type 1 diabetes (n = 1,656) in Finland were collected.

RESULTS

DKA was present in 19.4% of the case subjects, and 4.3% had severe DKA. In children aged 0–4, 5–9, and 10–14 years, DKA was present in 16.5, 14.8, and 26.4%, respectively (P < 0.001). Severe DKA occurred in 3.7, 3.1, and 5.9%, respectively (P = 0.048). DKA was present in 30.1% and severe DKA in 7.8% of children aged <2 years.

CONCLUSION

The overall frequency of DKA in children is low in Finland at diagnosis of type 1 diabetes. However, both children <2 years of age and adolescents aged 10–14 years are at increased risk of DKA.The incidence of diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes may be decreasing in developed countries (1,2).     

安全静脉留置针在院外急救中的应用

目的探讨安全静脉留置针输液在院外急救中的应用效果。方法将165例院前急救的患者随机分成留置针组(84例)和常规组(81例),对2组的补液畅通程度、脱针率、渗出/外渗率和堵塞率方面进行比较。结果留置针组在输液畅通程度显著性好于常规组(P<0.01),在脱针率(P<0.01)、渗出/外渗率(P<0.05)和阻塞率(P<0.01)方面显著性低于常规组。结论安全留置针输液在院外救护中值得推广。     

Safety, tolerability and satisfaction with tegaserod therapy in Asia-Pacific patients with irritable bowel syndrome with constipation

BACKGROUND AND AIM: The 5-HT(4) receptor agonist tegaserod (6 mg b.i.d.) provides significantly better overall multiple symptom relief compared with placebo in patients with irritable bowel syndrome with constipation (IBS-C). The clinical benefit and safety of tegaserod in IBS-C patients has been demonstrated worldwide in several studies. The aim of this study was to obtain further safety and tolerability data in patients with IBS in the Asia-Pacific region, and to assess patients' satisfaction and compliance with treatment and willingness to re-use tegaserod in a post-marketing setting. METHODS: A multicenter, single-arm, open-label trial was conducted at 869 outpatient centers in 10 countries. Men and women with IBS, whose predominant bowel symptom was not diarrhea (non-D-IBS), received tegaserod for 4-12 weeks. Safety and tolerability were assessed by recording adverse events (AE). Patients were questioned about compliance, satisfaction with treatment and willingness to use tegaserod in future. RESULTS: Data were available from 14 537 patients (18% men, 82% women). Four percent of patients reported at least one AE. The most common AE were diarrhea (2%) and abdominal pain (1%), and most treatment-related AE occurred in the first week of treatment. Serious AE (SAE) were observed in eight patients, and no deaths were reported. Most patients (79%) reported to be satisfied or very satisfied with treatment, and 76% stated they would use tegaserod in the future. Compliance was 97%. CONCLUSIONS: Tegaserod has a favorable safety and tolerability profile for treating non-D-IBS and IBS-C in men and women in the Asia-Pacific region. Satisfaction with tegaserod treatment can be expected in the majority of patients.     

Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192

OBJECTIVE: To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFbeta1 and TGFbeta2. RESULTS: Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). CONCLUSION: We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.     

Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients

The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with > 98% of those responding receiving > or = 28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days; failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times (P = 0.0259) and were more likely to die from fungal infection (P = 0.002) than were Scedosporium apiospermum-infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum-infected patients (54% response; MIC(50), 0.25 microg/ml) than for S. prolificans-infected patients (40% response; MIC(50), 4.0 microg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.     

A comparative study of clarithromycin modified release and amoxicillin/clavulanic acid in the treatment of acute exacerbation of chronic bronchitis

This phase III, investigator-blind, randomized, parallel-group study compared the efficacy and tolerability of clarithromycin modified release (MR) with those of amoxicillin/clavulanic acid in 250 adult outpatients with acute exacerbation of chronic bronchitis (AECB). Patients received either clarithromycin MR 500 mg once daily or amoxicillin/clavulanic acid 500 mg/125 mg three times daily for 7 days. Primary endpoints were sponsor-defined clinical response and pathogen outcome at the end of treatment. Secondary endpoints were sponsor-defined clinical response and pathogen outcome at study end, investigator-defined clinical response at end of treatment and end of study, resolution or improvement of signs and symptoms, eradication of baseline pathogens, serologic outcome for atypical pathogens, and occurrence of reinfection and superinfection. Adverse events and compliance were also evaluated. Clinical and bacteriologic outcomes with both treatments for all endpoints were statistically equivalent, as were total adverse events, although the incidences of digestive disturbances (13% vs 4%) and discontinuations due to adverse events (8 vs 2 patients; P≤.05) were significantly higher with amoxicillin/clavulanic acid. Ninety-five percent of patients receiving clarithromycin MR and 80% receiving amoxicillin/clavulanic acid were 100% compliant with medication (P≤.05). Clarithromycin MR and amoxicillin/clavulanic acid are both well tolerated and effective as therapy for AECB; however, clarithromycin produced fewer side effects and discontinuations and higher compliance rates.     

Relationship between plasma sialic acid concentration and microvascular and macrovascular complications in type 1 diabetes: the EURODIAB Complications Study

OBJECTIVE: To test the hypothesis that an increased plasma concentration of sialic acid, a marker of the acute-phase response, is related to the presence of diabetic micro- and macrovascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We investigated the relationship between plasma sialic acid concentration and nephropathy, retinopathy, neuropathy, and coronary heart disease (CHD) in a cross-sectional survey of 1,369 people with type 1 diabetes. Subjects were participants in the EURODIAB IDDM Complications Study, which involved 31 centers in 16 European countries. RESULTS: There was a significantly increasing trend of plasma sialic acid with severity of retinopathy (P < 0.001 in men) and with degree of urinary albumin excretion (P < 0.001 men, P < 0.01 women). Plasma sialic acid correlated with increasing plasma creatinine concentration (P < 0.009 men, P < 0.0002 women), and men with neuropathy had a higher plasma sialic acid concentration than those without (P < 0.006). There was no significant correlation between plasma sialic acid and CHD in either sex. Elevated plasma sialic acid concentrations were also associated with several risk factors for diabetic vascular disease: diabetes duration, HbA1c, plasma triglyceride and cholesterol concentrations, waist-to-hip ratio, hypertension and smoking (in men), and low physical exercise (in women). In multiple logistic regression analysis, plasma sialic acid was independently related to proliferative retinopathy and urinary albumin excretion rate in men. CONCLUSIONS: We conclude that an elevated plasma sialic concentration is strongly related to the presence of microvascular complications in type 1 diabetes, especially retinopathy and nephropathy. Further study of acute-phase response markers and mediators as indicators or predictors of diabetic microvascular complications is therefore justified.     

Hospitalization among diabetic children and adolescents and the general population in Germany. German Working Group for Pediatric Diabetology

OBJECTIVE: To compare hospitalization in a multicenter-based cohort of diabetic children and adolescents (aged 1-19 years) in Germany with that of the general population. RESEARCH DESIGN AND METHODS: Based on standardized documentation, hospital stays after manifestation were ascertained in diabetic subjects 1-19 years of age in 1997. Hospitalization data in the general German population were derived from official statistics. Incidence rates and numbers of hospital days were estimated. Ratios of hospitalization incidences and numbers of hospital days between the diabetic and the general population were calculated. Costs for hospital care in the German diabetic population in 1997 were determined. RESULTS: A total of 5,874 patients came from 61 pediatric centers (52% male, age [mean +/- SD] 12.2 +/- 4.3 years, diabetes duration 4.6 +/- 4.4 years). Hospitalization incidence rates and hospital days per person-year (95% CI) were 0.27 (0.25-0.29) and 1.80 (1.75-1.84) in the diabetic population and 0.0948 (0.0946-0.0949) and 0.6416 (0.6412-0.6420) in the general population. The standardized ratio of hospital incidences was 3.1 (2.9-3.2), and the ratio of numbers of hospital days was 2.8 (2.7-2.9). Costs for hospital care after manifestation were estimated to be $506 (U.S. dollars) per person-year and $12.4 million in the whole German diabetic population aged 1-19 years in 1997; including hospital stays at diabetes onset, total annual costs were $24 million ($970 per person-year). CONCLUSIONS: Diabetic children and adolescents in Germany had an approximately three times higher hospitalization risk and three times more hospital days than the age-matched general population. Including hospitalization at diabetes onset, the annual costs of hospital care for the German diabetic population aged 1-19 years amounted to approximately 1% of all costs for hospital care in this age-group. Thus, costs were largely overproportional (diabetes prevalence 0.1%).