Initial development of a questionnaire evaluating perceived benefits and barriers to pediatric clinical trials participation

ObjectiveTo evaluate perceived benefits and barriers to pediatric clinical trials participation to improve decision-making and enhance recruitment and retention among minority youth with chronic health conditions (sickle cell disease, asthma) and their caregivers.MethodsA questionnaire was developed based on the social ecological model using input from medical experts and community-based public health organizations. Parallel caregiver, adolescent/young adult (AYA; 16–39 years old), and child (8–15 years old) versions were field tested. Patients and caregivers completed the questionnaire, which included demographic items, perceived life stress and social desirability measures.ResultsExploratory factor analysis rendered a four-factor solution for the caregiver version (direct treatment benefit, mistrust of research/researchers, trust in healthcare team to engage in safe research, and opportunity cost) and the AYA version (mistrust/no direct benefit, safety, direct treatment benefit/practical considerations, and social support for research). Factor structures differed for SCD and asthma caregivers; results were equivocal for the child version. Summated subscales were not significantly associated with patient demographics or social desirability, but significant correlations with perceived life stress and prior participation in research were identified.ConclusionsWhile the factor structure should be confirmed with larger samples, findings indicate potential benefit, perceived harm due to mistrust of researchers, and logistics are primary factors in decision-making about participation in pediatric clinical trials. By addressing these benefits/barriers through adjustments to recruitment and informed consent procedures, researchers may address misperceptions of research, improve decision-making, and increase recruitment and retention particularly for ethnic minority children with chronic health conditions.     

Contribution of arterial stiffness and stroke volume to peripheral pulse pressure in ICU patients: an arterial tonometry study

Objective Peripheral arterial pulse pressure is increasingly used to assess hemodynamic status. Our aim was to test the respective influence of arterial stiffness, stroke volume, peripheral resistance, and various hemodynamic and demographic variables on peripheral pulse pressure in critically ill patients. Design Prospective study. Setting Medical intensive care unit of a university hospital. Interventions None. Patients 67 sinus rhythm patients (mean age 57 ± 17 years) of whom 17 received vasoactive agents. Measurements and results The stroke volume was calculated by Doppler echocardiography. Radial pressures were calibrated from systolic and diastolic brachial cuff pressures. Central aortic pressure was estimated by radial applanation tonometry. The arterial compliance was estimated from the aortic pressure curve using the area method and the arterial stiffness was calculated as 1/compliance. The influences of age, body surface area, arterial stiffness, stroke volume, peripheral resistance, and time intervals on peripheral pulse pressure were tested using univariate and multivariate analyses. The mean arterial pressure ranged from 42 to 113 mmHg. Peripheral pulse pressure (59 ± 17 mmHg) was higher than aortic pulse pressure (40 ± 14 mmHg, p < 0.001). In patients aged ≥ 60 years whose mean arterial pressure was ≥ 80 mmHg, peripheral pulse pressure was related to arterial stiffness (r ² = 0.41) and to stroke volume (multiple r ² = 0.90). A similar but weaker relationship was observed in the overall population (multiple r ² = 0.52). Conclusions In critically ill patients, and especially in aged subjects with hemodynamic stability, peripheral pulse pressure mainly reflected the combined influences of arterial stiffness and stroke volume. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Functional Electrical Stimulation—A New Therapeutic Approach to Enhance Exercise Intensity in Chronic Obstructive Pulmonary Disease Patients: A Randomized,Controlled Crossover Trial

Objective

To evaluate the effect of quadriceps functional electrical stimulation (FES)-cycling on exertional oxygen uptake ($\dot{\text{V}}$o₂) compared with placebo FES-cycling in patients with chronic obstructive pulmonary disease (COPD).

Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21) gene. To determine the mutational spectrum in the Tunisian CAH population, the CYP21 active gene was analyzed in 51 unrelated patients using our cascade strategy (digestion by restriction enzyme, sequencing). All patients had a classical form of 21-hydroxylase deficiency. Mutations were detected in over 94% of the chromosomes examined. The most frequent mutation in the Tunisian CAH population was found to be Q318X, with large prevalence (35.3%), in contrast to 0.5-13.8% described in other series. Incidence of other mutations does not differ, as previously described: large deletions (19.6%), mutation in intron 2 (17.6%), and I172N (10.8%). Four novel mutations were found in four patients with the salt-wasting form. These four novel mutations include three point mutations that have not been reported to occur in the CYP21P pseudogene: R483W, W19X, 2669insC, and one small conversion of DNA sequence from exon 5 to exon 8. Our results have shown a good genotype/phenotype correlation in the case of most mutations. This is the first report of screening for mutations of 21-hydroxylase gene in the Tunisian population and even in the Arab population.     

Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.     

Respiratory failure in the elderly patient

Respiratory failure frequently complicates the care of elderly patients with or without chronic lung disease. Recent advances in techniques and applications of noninvasive ventilation provide an exceedingly useful means of managing respiratory compromise, and the clinical utilization of noninvasive mechanical ventilation has transformed the prognosis of acute and chronic respiratory failure in this age group. The majority of elderly patients can recover from an acute respiratory failure episode if adequate support is provided, although some may require long-term ventilatory assistance. Such assistance may be provided in the home setting if an adequate support system is available. As the size of the elderly population grows, an increased number of elderly patients with multifactorial respiratory failure will undoubtedly require episodic or sustained ventilatory assistance, and noninvasive ventilation can be provided for various forms of acute and chronic respiratory failure, including advanced chronic obstructive pulmonary disease, other parenchymal lung disease, and chest wall deformities. Health care organizations must incorporate long-term care facilities with ventilatory support capabilities into their health management strategies.     

Relation of demographic, clinic and biochemical parameters to peritonitis in peritoneal dialysis

The relation of various demographic, clinical and biochemical parameters of peritoneal dialysis patients with peritonitis and other infections was evaluated. The age, gender, peritoneal dialysis (PD) period, educational status, peritonitis, exit site score, serum albumin, C-reactive protein (CRP), and triglyceride levels at the beginning and the last visit were recorded. Mean age of 32 patients was 45.1 years; PD period was 13.1 months. Albumin level was inversely proportional to the frequency of peritonitis. Patients with peritonitis had albumin levels that were lower at the last visit, and were independent of the CRP values at the start of PD and during follow-up. Significant correlation was detected between females and exit site scores. There was significant correlation between educational status and peritonitis. Albumin level at first visit was a factor that reduced the likelihood of peritonitis, and low levels obtained during follow-up constituted a risk for peritonitis. It was also shown that peritonitis risk tended to decrease inversely with education level.     

Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial

From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805).     

Effects of Nigella sativa on outcome of hepatitis C in Egypt

AIM: To evaluate the safety, efficacy and tolerability of Nigella sativa (N. sativa ) in patients with hepatitis C not eligible for interferon (IFN)-α. METHODS: Thirty patients with hepatitis C virus (HCV) infection, who were not eligible for IFN/ribavirin therapy, were included in the present study. Inclusion criteria included: patients with HCV with or without cirrhosis, who had a contraindication to IFN-α therapy, or had refused or had a financial constraint to IFN-α therapy. Exclusion criteria included: patients on IFN-α therapy, infection with hepatitis B or hepatitis Ⅰ virus, hepatocellular carcinoma, other malignancies, major severe illness, or treatment non-compliance. Various parameters, including clinical parameters, complete blood count, liver function, renal function, plasma glucose, total antioxidant capacity (TAC), and polymerase chain reaction, were all assessed at baseline and at the end of the study. Clinical assessment included: hepato and/ or splenomegaly, jaundice, palmar erythema, flapping tremors, spider naevi, lower-limb edema, and ascites. N. sativa was administered for three successive months at a dose of (450 mg three times daily). Clinical response and incidence of adverse drug reactions were assessed initially, periodically, and at the end of the study. RESULTS: N. sativa administration significantly improved HCV viral load (380808.7 ± 610937 vs 147028.2 ± 475225.6, P = 0.001) and TAC (1.35 ± 0.5 vs 1.612 ± 0.56, P = 0.001). After N. sativa administration, the following laboratory parameters improved: total protein (7.1 ± 0.7 vs 7.5 ± 0.8, P = 0.001), albumin (3.5 ± 0.87 vs 3.69 ± 0.91, P = 0.008), red blood cell count (4.13 ± 0.9 vs 4.3 ± 0.9, P = 0.001), and platelet count (167.7 ± 91.2 vs 198.5 ± 103, P = 0.004). Fasting blood glucose (104.03 ± 43.42 vs 92.1 ± 31.34, P = 0.001) and postprandial blood glucose (143.67 ± 72.56 vs 112.1 ± 42.9, P = 0.001) were significantly decreased in both diabetic and non-diabetic HCV patients. Patients with lower-limb edema de     

Interaction of angiotensin-converting enzyme and apolipoprotein E gene polymorphisms in ischemic stroke involving large-vessel disease

A relationship between apolipoprotein E (Apo E) genotype and angiotensin-converting enzyme (ACE) insertion-deletion (Ins-Del) mutation and stroke was suggested. We investigated the association of Apo E4 and ACE Ins/Del genotypes with stroke risk and changes in serum lipids in 228 consecutive Tunisian stroke patients, and 323 age-and gender-matched controls. Comparable frequencies of ACE Ins/Del alleles were seen between patients and controls. The prevalence of Apo ε3 allele and Apo E3/E3 were lower (P < 0.001), while the frequency of Apo ε4 allele and ε4-containing genotypes (E3/E4 and E4/E4) were elevated (P < 0.001) among patients. Higher proportion of Apo E4-carrying + ACE Del/Del positive cases were seen in young (<50 years) patients (P = 0.012), and was associated with large vessel stroke (P = 0.035). Mean serum cholesterol, LDL, HDL, and triglycerides were comparable between E4-containing and no E4-containing and ACE Del/Del-positive patients. Apo E4 and ACE Del/Del genotype combination substantially increase stroke risk, supporting the notion that interactions of multiple gene variants influence stroke pathogenesis.