Efficacy of Everolimus Combined with 177Lu-Dotatate in the Treatment of Neuroendocrine Tumors.

Background: Both everolimus and peptide receptor radionuclide therapy (PRRT) are approved as monotherapies for advanced neuroendocrine tumors (NETs). Research in animal models showed synergism between the two treatment modalities. This study aimed to evaluate the safety and efficacy of combining everolimus and PRRT in the treatment of unresectable NETs. Methods: Adult patients (≥18 years) with progressing and unresectable histologically confirmed grade 1-2 NETs of all origins were enrolled. Everolimus was started at a 5 mg daily dose and was increased after the initial three patients to 10 mg daily. Patients were treated concurrently with 177Lu-DOTATATE at an 8-week interval, with planned four cycles. Safety was the primary endpoint, with response rate and progression-free survival (PFS) being secondary. Results: Eleven patients were enrolled. The trial was terminated early for poor accrual. The median age was 51 years (18-64), and 4 were males. The median number of cycles of 177Lu-DOTATATE was 3, and the median cumulative dose was 300 mCi. The most frequent grade 1-2 toxicities were stomatitis (90.9%) and nausea (72.7%). Less frequent were fatigue (63.6%), anorexia, diarrhea, and skin changes (each at a 36.4% rate). Grade 3 toxicities occurred in 36% (fatigue, infection, pneumonitis, neutropenia, and stroke). No patient developed grade 4 toxicity. Treatment was stopped because of progression in three patients, and toxicity in another three patients, in addition, in four patients due to therapy interruption and in one patient who developed stroke. One patient achieved partial response, and nine had stable disease. One patient developed disease progression. At a median follow-up of 18.9 months, three died and one was lost to follow-up. The median PFS was 23.3 months. Conclusions: The combination of everolimus at a dose of 10 mg daily and 177Lu-DOTATATE appears not to be feasible. A larger trial at a lower dose of everolimus is warranted.

Variability of emergency color codes for critical events between hospitals in Riyadh.

BACKGROUND: Emergency color codes were developed to alert healthcare personnel in a hospital to critical situations. They are often developed independently by each hospital, leading to variability. This could be a source of confusion to healthcare personnel, who move frequently between hospitals and may work at multiple hospitals. This study evaluated the variability of emergency codes for different critical events in hospitals in Riyadh. METHODS: A prospective, cross-sectional survey was carried out on a representative sample of hospitals. Twenty-four of 28 hospitals took part in the study. Semi-structured questionnaires were completed by the Quality/Safety Department of each hospital, on general hospital characteristics, emergency department characteristics, code-response mock-up, code determination, emergency codes used and code meanings. RESULTS: Thirty-four different codes were used across hospitals. The codes used most variably were yellow (10 meanings), orange, black, green (7 meanings each), and gray (5 meanings), while the most consistently used code was 'Code Red' for 'Fire' in 75% of hospitals. Another source of variability was the use of non-color codes, representing 7.7% of total codes. CONCLUSIONS: There is large variability in the type and meaning of emergency codes between hospitals in Riyadh City, reflecting a lack of standardization. Hospitals use color and non-color emergency codes, which could cause confusion to responders and mitigate the effectiveness and speed of response in critical events.

Effect of mobile phone short text messages on glycemic control in type 2 diabetes.

BACKGROUND: Mobile phone text messaging has rapidly become a socially popular form of communication. Several studies showed that mobile phone might offer a useful means of providing information between clinic visits and might increase adherence to diabetes therapy regimens. OBJECTIVES: We conducted a study to evaluate the effect of mobile phone short message service (SMS) on glycemic control in Saudi patients with type 2 diabetes. PATIENTS AND METHODS: One hundred patients (mean age, 41 ± 9.5 years) were selected at the Security Forces Hospital, Riyadh, Saudi Arabia, and provided with daily educational, reminding SMS messages for four months. Glycosylated hemoglobin (HbA1c) level, frequency of hypoglycemic and hyperglycemic attacks, and compliance with blood glucose monitoring were recorded before and after the trial. RESULTS: In addition to significant improvement in patients' knowledge, mean fasting blood glucose level improved from 8.60 ± 3.16 to 7.77 ± 3.11 mmol/L and mean HbA1c decreased from 9.9% ± 1.8% to 9.5% ± 1.7%. CONCLUSIONS: Mobile phone text messaging increased adherence to diabetes therapy and improved the clinical outcome in Saudi patients with type 2 diabetes.

Effect of mobile phone short text messages on glycaemic control in children with type 1 diabetes.

We conducted a feasibility study of a mobile phone messaging service for children and adolescents with type 1 diabetes. Two hundred children with type 1 diabetes took part in a six-month trial. The children were provided - through their parents - with daily information messages, with weekly interactive messages, and on request, with multimedia video messages about procedures related to diabetes care. During the study, approximately 30,000 information messages and 2800 interactive messages were sent. One month before the trial, the mean fasting blood glucose level of the children was 150 mg/dl. After the trial, the mean fasting blood glucose level was 133 mg/dl (P < 0.001). There were also significant reductions in post prandial blood glucose level, HbA1c, frequency of simple hypoglycaemic attacks and frequency of blood glucose monitoring. A before and after questionnaire showed that the parents' knowledge of diabetes had improved significantly during the trial. Mobile phone text messaging offers a useful means of contact between clinic visits. The results of the trial suggest that it increases adherence to diabetes therapy and improves clinical outcomes in children and adolescents with type 1 diabetes.

Covariate-adjusted confidence interval for the intraclass correlation coefficient.

A crucial step in designing a new study is to estimate the required sample size. For a design involving cluster sampling, the appropriate sample size depends on the so-called design effect, which is a function of the average cluster size and the intracluster correlation coefficient (ICC). It is well-known that under the framework of hierarchical and generalized linear models, a reduction in residual error may be achieved by including risk factors as covariates. In this paper we show that the covariate design, indicating whether the covariates are measured at the cluster level or at the within-cluster subject level affects the estimation of the ICC, and hence the design effect. Therefore, the distinction between these two types of covariates should be made at the design stage. In this paper we use the nested-bootstrap method to assess the accuracy of the estimated ICC for continuous and binary response variables under different covariate structures. The codes of two SAS macros are made available by the authors for interested readers to facilitate the construction of confidence intervals for the ICC. Moreover, using Monte Carlo simulations we evaluate the relative efficiency of the estimators and evaluate the accuracy of the coverage probabilities of a 95% confidence interval on the population ICC. The methodology is illustrated using a published data set of blood pressure measurements taken on family members.

Immediate and long-term results of mitral balloon valvotomy for restenosis following previous surgical or balloon mitral commissurotomy.

This study compared immediate with long-term results of mitral balloon valvotomy (MBV) in patients who underwent MBV as an initial procedure versus those who underwent repeat MBV. Fifty-six patients who were a mean age of 28 +/- 8.8 years (group A) and had mitral restenosis after surgical or balloon commissurotomy underwent MBV and were compared with 524 patients who were a mean age of 31 +/- 11 years (group B) and underwent MBV as an initial procedure. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up for 0.5 to 15 years after MBV. No deaths or technical failure were encountered after MBV. Mitral regurgitation >2/4 occurred in 1 patient (2%) in group A and in 9 patients (2%) in group B (p = 0.24). Fifty-two of 56 patients (93%) in group A had good immediate results (mitral valve area >or=1.5 cm(2), mitral regurgitation <2/4), as did 504 of 524 patients (96%) in group B (p = 0.4). Actuarial values for freedom from restenosis at 10 years were 58 +/- 7% for group A versus 69 +/- 3% for group B (p = 0.18). Ten-year event-free survival rate was 54 +/- 7% for group A versus 80 +/- 3% for group B (p <0.005). The predictors of event-free survival were age (p = 0.003), echocardiographic score (p <0.0001), and baseline atrial fibrillation (p = 0.01). In conclusion, MBV is safe and provides good immediate results in patients who have restenosis. Long-term results are inferior compared with de novo mitral stenosis but is still satisfactory. More than 50% of patients remained improved at 10 years, thus enabling the operation or reoperation to be deferred.